整合素受体配体专利检索-关节成形术手术专利检索查询-专利查询网 (2024)

本发明涉及一种能够与整合素受体结合的新化合物，以及它们的 制备和用途。

整合素是一种细胞表面的糖蛋白受体，它能够调节相同或不同类 型细胞之间以及细胞和细胞外基质蛋白之间的相互作用。在生理学过 程，例如胚胎发生、止血、伤口愈合、免疫应答和组织构造的形成/维 护中都会涉及到它们。

细胞粘附分子基因的表达紊乱和受体功能的失调可能会成为大量 疾病发病机理的原因之一，这些疾病如肿瘤、血栓栓塞现象、心血管 疾病、肺部疾病、ZNS、肾、胃肠道疾病或炎症。

整合素是分别由α和β跨膜亚单元组成的异源二聚体，所述亚单元 可以是非共价性连接的。迄今为止，已经鉴别了16种不同的α和8种 不同β亚单元和22种不同的组合。

整合素αvβ3，也被称为玻连蛋白受体，能够调节与大量配体—血浆 蛋白、细胞外基质蛋白、细胞表面蛋白的粘合，配体中的大多数都含 有氨基酸序列RGD(Cell，1986，44，517-518；Science1987，238， 491-497)，例如玻连蛋白、纤维蛋白原、纤连蛋白、维勒布兰德氏因 子、血小板反应蛋白、骨桥蛋白、层粘连蛋白、胶原、凝血酶、腱生 蛋白、MMP-2、骨唾液蛋白II、各种病毒、真菌、寄生虫的和细菌蛋 白、天然的整合素拮抗体例如解整合蛋白、神经毒素-Mambin-和水蛭 蛋白-Decorsin，Ornatin-和一些非-RGD配体，例如Cyr-61和PECAM-1 (L.Piali，J.CellBiol.1995，130，451-460；Buckley，J.Cell Science1996，109，437-445，J.Biol.Chem.1998，273，3090-3096)。

好几种整合素受体显示出与含有RGD基序配体的交叉活性。这样， 整合素αIIbβ3，也被称为血小板纤维蛋白原受体、识别纤连蛋白、玻连 蛋白、血小板反应蛋白、维勒布兰德氏因子和纤维蛋白原。

尤其在内皮细胞、血小板、单核细胞/巨噬细胞、平滑肌细胞、一 些B细胞、成纤维细胞、破骨细胞和各种肿瘤细胞例如黑瘤、成胶质 细胞瘤、肺、乳腺、前列腺和膀胱癌、骨肉瘤或成神经细胞瘤上表达 整合素αvβ3。

在各种病理状态下例如前血栓形成状态，血管损伤情形、肿瘤生 长或转移或再灌注，和在活性细胞上，特别在内皮细胞、平滑肌细胞 或巨噬细胞上能够观察到表达的增加。

尤其在下列病理状态下已经测出整合素αvβ3的参与：

心血管疾病例如动脉粥样硬化、血管损伤后的再狭窄和血管成形 术(新内膜形成，平滑肌细胞移植和增生)(J.Vasc.Surg.1994，19， 125-134；Circulation1994，90，2203-2206)，

急性肾衰(KidneyInt.1994，46，1050-1058；Proc.Natl.Acad. Sci.1993，90，5700-5704；KidneyInt.1995，48，1375-1385)，

与血管生成有关的微血管病，例如糖尿病性视网膜病或类风湿性 关节炎(Ann.Rev.Physiol1987，49，453-464；Int.Ophthalmol. 1987，11，41-50；Cell1994，79，1157-1164；J.Biol.Chem. 1992，267，10931-10934)，

动脉血栓形成，

中风(PhaseIIStudienmitReoPro，CentocorInc.，欧洲中 风会议第8次年刊)，

癌，例如肿瘤转移或肿瘤生长(肿瘤诱导的血管生成)(Cell1991， 64，327-336；Nature1989，339，58-61；Science1995，270，1500- 1502)，

骨质疏松症(破骨细胞的增生、趋化性和附着后对骨基质的骨吸收) (FASEBJ.1993，7，1475-1482；Exp.CellRes.1991，195，368-375， Cell1991，64，327-336)，

高血压(Am.J.Physiol.1998，275，H1449-H1454)，牛皮癣(Am. J.Pathol.1995，147，1661-1667)，

甲状旁腺机能亢进，

佩吉特疾病(J.Clin.Endocrinol.Metab.1996，81，1810- 1820)，

恶性高钙血症(CancerRes.1998，58，1930-1935)，

转移性的溶骨损害(Am.J.Pathol.1997，150，1383-1393)，

病原体蛋白(例如HIV-1毒素抗毒素(tat))诱导的过程(例如血 管生成，卡波氏肉瘤)(Blood1999，94，663-672)，

炎症(J.AllergyClin.Immunol.1998，102，376-381)，

心力衰竭、CHF和用于抗病毒、杀寄生虫、抗真菌或抗细菌治疗和 预防(粘连和内化)(J.Infect.Dis.1999，180，156-166；J. Virology1995，69，2664-2666；Cell1993，73，309-319)。

由于其关键的作用，含有低分子量的整合素αvβ3配体的药物制剂 具有重大的治疗和诊断价值并且尤其是用于所提到的适应征。

有益的αvβ3整合素受体配体能够以增加了的亲合力与整合素αvβ3 受体结合。

特别有益的αvβ3整合素受体配体另外也对整合素αvβ3具有增高的 选择性，并且对整合素αIIbβ3的作用降低至少10倍，优选至少100倍。

大量的化合物例如抗αvβ3-单克隆抗体、含有RGD结合序列的肽、 天然的含RGD的蛋白(例如解整合素)和低分子量化合物，已经显示 了整合素αvβ3拮抗作用，并且已经证实了体内的有益作用(FEBSLetts 1991，291，50-54；J.Biol.Chem.1990，265，12267-12271；J.Biol. Chem.1994，269，20233-20238；J.CellBiol1993，51，206-218；J. Biol.Chem.1987，262，17703-17711；Bioorg.Med.Chem. 1998，6，1185-1208)。

WO99/30713公开了1，3-取代的四氢嘧啶-2(1H)-酮衍生物和哌啶 -2-酮衍生物，WO99/31099公开了1，3-取代的咪唑啉-2-酮衍生物， WO98/35949公开了2，6-取代的2H-1，4-苯并噁嗪-3(4H)-酮衍生物， WO9800395和WO9723451公开了O-取代的酪氨酸衍生物，EP710657 和EP741133公开了3，5-取代的1，3-噁唑烷-2-酮，以及WO97/37655 公开了作为αvβ3整合素受体的拮抗剂的异吲哚。

本发明的一个目的是提供一种新的具有有益性能的整合素受体配体。 我们已经发现通过化学式I的化合物可以实现这种目的：

B-G-LI 其中B、G和L具有下列含义： L是化学式IL的结构单元

-U-TIL 其中 T是COOH基或者可水解成COOH的基团，并且 -U-是 -(CRL1RL2)a-(VL)b-(CRL3RL4)c-(WL)d-(CRL5RL6)e-(XL)f-(CRL7RL8)g-其中 a，c，e，g分别是0，1，2，或3， b，d，f分别是0或1， RL1，RL2，RL3，RL4，RL5，RL6，RL7，RL8分别是氢原子，卤素，羟基， 支链或直链的、可以被取代或不被取代的C1-C6-烷基-，C2-C6-烯基-， C2-C6-炔基或者C1-C6-亚烷基-C3-C7-环烷基，-(CH2)w-(YL)y-RL9基，可 以被取代的或不被取代的C3-C7-环烷基，芳基，芳烷基，杂芳基或杂 芳基烷基或者，在每种相互独立的情况中，两个基团RL1和RL2或RL3和 RL4或RL5和RL6或RL7和RL8一起是3-至7-元、被取代的或不被取代的、 饱和或不饱和的碳环或杂环，该杂环可含有选自O、N和S组中的至多 三个杂原子， w是0、1、2、3或4， y是0或1 YL是 -CO-，-CO-N(RY1)-，-N(RY1)-CO-， -N(RY1)-CO-N(RY1*)-， -N(RY1)-CO-O-，-O-，-S-，-SO2-， -SO2-N(RY1)-，-SO2-O-， -CO-O-，-O-CO-，-O-CO-N(Ry1)-， -N(RY1)-或 -N(RY1)-SO2-，

RY1，RY1*

分别是氢，支链或直链的、被取代或不被取代的C1-C6-烷基-，C1- C6-烷氧基烷基，C2-C6-烯基-，C3-C12-炔基-，CO-C1-C6-烷基-，CO-O- C1-C6-烷基或SO2-C1-C6-烷基或被取代的或不被取代的C3-C7-环烷基-， 芳基，芳烷基-，CO-O-亚烷基-芳基-，CO-亚烷基-芳基-，CO-芳基， SO2-芳基-，杂芳基，CO-杂芳基-或SO2-亚烷基-芳基，

RL9是氢，或者羟基，CN，卤素，支链或直链的、被取代的或不被 取代的C1-C6-烷基，被取代或不被取代的C3-C7-环烷基-，芳基-，杂 芳基或芳烷基，不被取代或被C1-C4-烷基或芳基取代的C2-C6-炔基或 C2-C6-烯基，被取代或不被取代C6-C12-二环烷基，C1-C6-亚烷基-C6-C12- 双环烷基-，C7-C20-三环烷基-，或C1-C6-亚烷基-C7-C20-三环烷基，或 3-至8-元、饱和或不饱和杂环并且该杂环由至多3个相同或不同基团 取代并含有至多三个不同或相同的选自O、N、S的杂原子，其中两个 基团可能一起形成稠合的，饱和的、不饱和的或芳香碳环或杂环，该 杂环可含有至多3个不同或相同的选自O、N、S的杂原子，并且该环 可能被取代或不被取代，或者另一被取代或不被取代的、饱和的、不 饱和的或芳香环可稠合到该环上，或者RL9基与RY1或RY1*形成饱和或 不饱和的C3-C7-杂环，该杂环还可以含有至多两个另外的选自O、S或 N的杂原子，

WL是被取代的或不被取代的4-至11-元单环或多环脂族烃或芳香 烃，它含有至多6个双键和至多6个选自于N、O、S中的杂原子，

VL，XL，

分别是-CO-，-CO-NRL10-，-NRL10-CO-，

-S-，-SO-，-SO2-，-SO2-NRL10-，-NRL10-SO2-，-CS-，

-CS-NRL10-，-NRL10-CS-，-CS-O-，-O-CS-，-CO-O-，

-O-CO-，-O-，亚乙炔基，-CHRL11-O-CHRL12-，

-C(＝CRL11RL12)-，-CRL11＝CRL12-，-CRL11(ORL13)-CHRL12-，

-CHRL11-CRL12(ORL13)-，-CH(NRL14-SO2-RL15)-，

-CH(NRL14-CO-RL15)-，-CH(NRL14-CO-ORL16)-，

CH(NRL14-CO-NRL14′RL15)-，-CH(CO-RL15)-，-CH(CO-ORL16)-

或CH(CO-NRL14RL15)-，

RL10是氢，支链或直链、被取代的或不被取代的C1-C6-烷基-，C1- C6-烷氧基烷基-，C2-C6-烯基-，C3-C12-炔基-，CO-C1-C6-烷基-，CO- O-C1-C6-烷基-，SO2-C1-C6-烷基或被取代的或不被取代的C3-C7-环烷基， CO-O-亚烷基-芳基-，CO-亚烷基-芳基，芳烷基-，CO-芳基-，SO2-芳 基-，杂芳基-，CO-杂芳基-，杂芳基烷基-或SO2-亚烷基-芳基，或者 RL10和选自于RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8中的一个基团一 起可以是含有至多5个相同或不同的O、N或S杂原子的被取代的或不 被取代的4-至8-元杂环，

RL11，RL12

分别是氢，羟基，支链或直链、被取代的或不被取代的C1-C6-烷 基-，C1-C4-烷氧基-，C2-C6-烯基-，C2-C6-炔基-或亚烷基-环烷基或者 被取代的或不被取代的C3-C7-环烷基-，芳基-，芳烷基-，杂芳基-或 杂芳基烷基，

RL13是氢、支链或直链、被取代的或不被取代的C1-C6-烷基-，C2- C6-烯基-，C2-C6-炔基-或亚烷基-环烷基或被取代的或不被取代的C3- C7-环烷基-，芳基-，芳烷基-，杂芳基-或杂芳基烷基，

RL14，RL14’

分别是氢，支链或直链、被取代的或不被取代的C1-C6-烷基-，C1- C6-烷氧烷基-，C2-C6-烯基，C3-C12-炔基，CO-C1-C6-烷基-，CO-O-C1- C6-烷基-，C1-C6-亚烷基-C3-C7-环烷基，或SO2-C1-C6-烷基或被取代的 或不被取代的C3-C7-环烷基-，CO-O-亚烷基-芳基-，CO-亚烷基-芳基-， 芳基-，CO-芳基，SO2-芳基-，杂芳基，CO-杂芳基-，杂芳基烷基-，芳 烷基或SO2-亚烷基芳基，

RL15是支链或直链、被取代的或不被取代的C1-C6-烷基-，烷氧基 烷基-，C1-C6-亚烷基-C3-C7-环烷基，C6-C12-双环烷基-，C1-C6-亚烷基 -C6-C12-双环烷基-，-C7-C20-三环烷基-或C1-C6-亚烷基-C7-C20-三环烷 基，由至多3个相同或不同基团取代的C3-C7-环烷基-，芳基-，芳烷 基-，杂芳基烷基或3-至8-元、饱和、不饱和或芳香杂环基，该杂环 可含有至多三个不同或相同的O、N、S的杂原子，其中两个基团一起 可能是稠合的、饱和、不饱和或芳香碳环或杂环，该杂环可含有至多 3个不同或相同的O、N、S杂原子，而且该环可能被取代或不被取代， 或者另一个被取代的或不被取代的饱和、不饱和或芳香环可稠合到该 环上，或者RL15基与RL14或RL14*形成饱和或不饱和的任选含有至多两 个另外的选自O、S或N中的杂原子的C3-C7-杂环，和

RL16是支链或直链、被取代的或不被取代的C1-C6-烷基-，烷氧基 烷基或C1-C6-亚烷基-C3-C7-环烷基或被取代的或不被取代的C3-C7-环 烷基，芳基，芳烷基，杂芳基或杂芳基烷基，

G是具有化学式IG的结构单元 其中，结构单元G可在两个取向构建入，和

ZG是氧、硫或NRG3，

RG1，RG2

分别是氢，CN，NO2，卤素，支链或直链的、被取代的或不被取代 的C1-C6-烷基-，C2-C6-烯基或C2-C6-炔基，支链或直链、被取代的或 不被取代的C1-C4-亚烷基-ORG4，C1-C4-亚烷基-CO-ORG4，C1-C4-亚烷基- CO-RG4，C1-C4-亚烷基-SO2-NRG5RG6，C1-C4-亚烷基-CO-NRG5RG6，C1-C4- 亚烷基-NRG5RG6或C1-C4-亚烷基-SRG4，被取代的或不被取代的C3-C7-环 烷基，C3-C7-杂环烷基，C3-C7-杂环烯基，C1-C4-亚烷基-C3-C7-环烷基， C1-C4-亚烷基-C3-C7-杂环烷基或C1-C4-亚烷基-C3-C7-杂环烯基，被取 代的或不被取代的芳基，芳烷基，杂芳基或杂芳烷基，-S-RG4，-O-RG4， -SO-RG4，-SO2-RG4，-CO-ORG4，-O-CO-RG4，-O-CO-NRG5RG6，-SO2-NRG5RG6， -CO-NRG5RG6，-NRG5RG6，CO-RG4，或RG1和RG2一起是被取代的或不被取 代的、饱和的、不饱和的或芳香的3-至9-元碳环、多碳环、含有至多 4个选自O、N、S的杂原子的杂环或杂多环。

RG3是氢，羟基，CN，支链或直链的、被取代的或不被取代的C1-C6- 烷基或C1-C4-烷氧基或被取代的或不被取代的C3-C7-环烷基-，-O-C3- C7-环烷基，芳基-，-O-芳基，芳烷基或-O-亚烷基-芳基。

RG4是氢，支链或直链被取代的或不被取代的C1-C8-烷基，C2-C6- 烯基，C2-C6-炔基，C1-C5-亚烷基-C1-C4-烷氧基-，单-和双-烷基氨基 亚烷基-或酰基氨基亚烷基或被取代的或不被取代的芳基，杂环烷基-， 杂环烯基，杂芳基，C3-C7-环烷基-，C1-C4-亚烷基-C3-C7-环烷基-，芳 烷基-，C1-C4-亚烷基-杂环烷基-，C1-C4-亚烷基-杂环烯基或杂芳基烷 基，

RG5，RG6

分别是氢，支链或直链被取代的或不被取代的C1-C8烷基，C2-C6- 烯基，C2-C6-炔基，C1-C5-亚烷基-C1-C4-烷氧基，单-和双烷基氨基亚 烷基或酰基氨基亚烷基，被取代的或不被取代的芳基，杂环烷基，杂 环烯基，杂芳基，C3-C7-环烷基-，C1-C4-亚烷基-C3-C7-环烷基-，芳烷 基-，C1-C4-亚烷基-杂环烷基，C1-C4-亚烷基-杂环烯基-或杂芳烷基，或 -SO2-RG4，-CO-ORG4，-CO-NRG4RG4*或-CO-RG4，和

RG4*是不同于RG4的RG4基，

B是含有至少一个原子的结构单元，这个原子在生理学条件下作为 氢受体可形成氢键，其中至少一个氢受体原子沿结构单元骨架沿最短 的可能途径与结构单元G之间具有4至13原子键的间隔，

和生理学上可接受的盐、前体药物和对映体纯的或非对映体纯的 和互变异构的形式。

除非另外说明，对于本发明中的所有基团或取代基卤素基团是指 如F、Cl、Br或I。

被取代的或不被取代的基团是指相应的未取代和取代过的基团。 对于本发明内的所有被取代的基团来说，如果没有详细说明取代基， 那么相互独立地有至多5个取代基，例如选自下列基团：

-NO2，-NH2，-OH，-CN，-COOH，-O-CH2-COOH，卤素，支链或直 链被取代的或不被取代的C1-C4-烷基，例如甲基，CF3，C2F5或CH2F，支 链或直链、被取代的或不被取代的-CO-O-C1-C4-烷基，C3-C7-环烷基， C1-C4-烷氧基，C1-C4-烷硫基，-NH-CO-O-C1-C4-烷基，-O-CH2-COO-C1- C4-烷基，-NH-CO-C1-C4-烷基，-CO-NH-C1-C4-烷基，-NH-SO2-C1-C4-烷 基，-SO2-NH-C1-C4-烷基，-N(C1-C4-烷基)2，-NH-C1-C4-烷基，或- SO2-C1-C4-烷基，例如-SO2-CF3，被取代的或不被取代的-NH-CO-芳基， -CO-NH-芳基，-NH-CO-O-芳基，-NH-CO-O-亚烷基-芳基，-NH-SO2-芳 基，-SO2-NH-芳基，-CO-NH-苄基，-NH-SO2-苄基或-SO2-NH-苄基，被 取代的或不被取代的-SO2-NR4R5或-CO-NR4R5基，R4和R5可相互独立地 具有如本文以后的RL14的含义，或者R4和R5两个基团共同为3-至6- 元的被取代的或不被取代的饱和、非饱和或芳香杂环，该杂环除了环 氮原子之外，还可以含最多3个其它的不同的或相同的O、N、S杂原 子，并且任选在该杂环上取代的两个基团一起是稠合的、饱和、不饱 和或芳香碳环或杂环，该杂环可含有至多3个不同或相同的O、N、S杂原子，并且该环可能被取代或不被取代，或另一被取代的或不被取 代的环可稠合到该环上。

对本发明的所有末端键合的、取代的杂芳基和杂芳烷基来说，除 了前述列出的取代基外，杂芳基部分的两个取代基可形成稠合的5-至 7-元、不饱和的或芳香碳环。

结构单元L中的T是指COOH基或能够水解成COOH的基团。能够 水解成COOH的基团是指在水解后转化成COOH基的基团。

所提到的作为能够水解成COOH的基团T的例子是下式基团

其中R1具有以下含义：

a)OM，其中M是金属阳离子，例如碱金属阳离子如锂、钠、钾， 当量的碱土金属阳离子如钙、镁和钡，或者环境上相容的有机铵离子 如伯、仲、叔或季C1-C4-烷基铵或铵离子，例如ONa，OK或OLi，

b)支链或直链的、被卤素取代的或不被取代的C1-C8-烷氧基，例 如甲氧基，乙氧基，丙氧基，1-甲基乙氧基，丁氧基，1-甲基-丙氧 基，2-甲基丙氧基，1，1-二甲基乙氧基，尤其是甲氧基，乙氧基，1- 甲基乙氧基，戊氧基，己氧基，庚氧基，辛氧基，二氟甲氧基，三氟 甲氧基，氯代二氟甲氧基，1-氟乙氧基，2-氟乙氧基，2，2-二氟乙氧 基，1，1，2，2-四氟乙氧基，2，2，2-三氟乙氧基，2-氯-1，1，2-三氟乙 氧基或五氟乙氧基

c)支链或直链的、被卤素取代的或不被取代的C1-C4-烷基硫基例 如甲硫基，乙硫基，丙硫基，1-甲基乙硫基，丁硫基，1-甲基丙硫基，2- 甲基丙硫基或1，1-二甲基乙硫基

d)被取代的或不被取代的-O-亚烷基-芳基，例如-O-苄基

e)R1此处为-(O)ml-N(R2)(R3)，其中ml是0或1，R2和R3可以相 同或也可以不同，具有以下含义：

氢，

支链或直链的、被取代的或不被取代的

C1-C6-烷基，例如，甲基，乙基，丙基，1-甲基乙基，丁基，1- 甲基丙基，2-甲基丙基，1，1-二甲基乙基，戊基，1-甲基丁基，2-甲 基丁基，1，2-二甲基丙基，1，1-二甲基丙基，2，2-二甲基丙基，1-乙 基丙基，己基，1-甲基戊基，1，2-二甲基丁基，1，3-二甲基丁基，2，3- 二甲基丁基，1，1-二甲基丁基，2，2-二甲基丁基，3，3-二甲基丁基， 1，1，2-三甲丙基，1，2，2-三甲基丙基，1-乙基丁基，2-乙基丁基或1- 乙基-2-甲基丙基或相应的被取代的基团，优选甲基，乙基，丙基，丁 基或异丁基，

C2-C6-烯基，例如乙烯基，2-丙烯基，2-丁烯基，3-丁烯基，1- 甲基-2-丙烯基，2-甲基-2丙烯基，2-戊烯基，3-戊烯基，4-戊烯基，1- 甲基-2-丁烯基，2-甲基-2-丁烯基，3-甲基-2-丁烯基，1-甲基-3- 丁烯基，2-甲基-3-丁烯基，3-甲基-3-丁烯基，1，1-二甲基-2-丙烯 基，1，2-二甲基-2-丙烯基，1-乙基-2-丙烯基，2-己烯基，3-己烯基， 4-己烯基，5-己烯基，1-甲基-2-戊烯基，2-甲基-2-戊烯基，3-甲基 -2-戊烯基，4-甲基-2-戊烯基，3-甲基-3-戊烯基，4-甲基3-戊烯基， 1-甲基-4-戊烯基，2-甲基-4-戊烯基，3-甲基-4-戊烯基，4-甲基-4- 戊烯基，1，1-二甲基-2-丁烯基，1，1-二甲基-3-丁烯基，1，2-二甲基 -2-丁烯基，1，2-二甲基-3-丁烯基，1，3-二甲基-2-丁烯基，1，3-二 甲基-3-丁烯基，2，2-二甲基-3-丁烯基，2，3-二甲基-2-丁烯基，2，3- 二甲基-3-丁烯基，1-乙基-2-丁烯基，1-乙基-3-丁烯基，2-乙基-2- 丁烯基，2-乙基-3-丁烯基，1，1，2-三甲基-2-丙烯基，1-乙基-1-甲 基-2-丙烯基和1-乙基-2-甲基-2-丙烯基，尤其2-丙烯基，2-丁烯基， 3-甲基-2-丁烯基或3-甲基-2-戊烯基或相应的被取代的基团，

C2-C6-炔基，例如乙炔基，2-丙炔基，2-丁炔基，3-丁炔基，1- 甲基-2-丙炔基，2-戊炔基，3-戊炔基，4-戊炔基，1-甲基-3-丁炔基， 2-甲基-3-丁炔基，1-甲基-2-丁炔基，1，1-二甲基-2-丙炔基，1-乙 基-2-丙炔基，2-己炔基，3-己炔基，4-己炔基，5-己炔基，1-甲基- 2-戊炔基，1-甲基-2-戊炔基，1-甲基-3-戊炔基，1-甲基-4-戊炔基， 2-甲基-3-戊炔基，2-甲基-4-戊炔基，3-甲基-4-戊炔基，4-甲基-2- 戊炔基，1，1-二甲基-2-丁炔基，1，1-二甲基-3-丁炔基，1，2-二甲基 -3-丁炔基，2，2-二甲基-3-丁炔基，1-乙基-2-丁炔基，1-乙基-3-丁 炔基，2-乙基-3-丁炔基和1-乙基-1-甲基-2-丙炔基，优选2-丙炔基， 2-丁炔基，1-甲基-2-丙炔基或1-甲基-2-丁炔基，或相应的取代的基 团，

C3-C8-环烷基，例如环丙基，环丁基，环戊基，环己基和环庚基，环 辛基或相应的被取代的基团，

或苯基，可以由以下基团取代一或多次，例如取代一至三次：卤素， 硝基，氰基，C1-C4-烷基，C1-C4-卤代烷基，C1-C4-烷氧基，C1-C4-卤 代烷氧基或C1-C4-烷基硫基，例如2-氟苯基，3-氯苯基，4-溴苯基，2- 甲基苯基，3-硝基苯基，4-氰基苯基，2-三氟甲基苯基，3-甲氧基苯 基，4-三氟乙氧基苯基，2-甲硫基苯基，2，4-二氯苯基，2-甲氧基-3- 甲基苯基，2，4-二甲氧基苯基，2-硝基-5-氰基苯基，2，6-二氟苯基，

或者R2和R3共同形成的C4-C7-亚烷基链，它是闭环的、可被例如 C1-C4-烷基取代或不被取代并且可含有选自氧、硫或氮的杂原子，例如 -(CH2)4-，-(CH2)5-，-(CH2)6-，-(CH2)7-，-(CH2)2-O-(CH2)2-，-CH2- S-(CH2)3-，-(CH2)2-O-(CH2)3-，-NH-(CH2)3-，-CH2-NH-(CH2)2-， -CH2-CH＝CH-CH2-，-CH＝CH-(CH2)3-，-CO-(CH2)2-CO-或-CO-(CH2)3-CO-。

优选的T基团是-COOH，-CO-O-C1-C8-烷基或-CO-O-苄基。

结构单元-U-中的系数a，c，e和g相互独立地是0，1，2或3，优 选0，1或2。

而且，优选结构单元-U-的a，c，e和g的系数总和小于7。

尤其优选结构单元-U-中，a，c，e和g相互独立地是0或1。

对于RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8来说，优选的卤原子 是氟。

对于结构单元L中的RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8来说， 支链或直链C1-C6-烷基分别是甲基，乙基，丙基，1-甲基乙基，丁基，1- 甲基丙基，2-甲基丙基，1，1-二甲基乙基，戊基，1-甲基丁基，2-甲 基丁基，1，2-二甲基丙基，1，1-二甲基-丙基，2，2-二甲基丙基，1- 乙基丙基，己基，1-甲基戊基，1，2-二甲基丁基，1，3-二甲基丁基， 2，3-二甲基丁基，1，1-二甲基丁基，2，2-二甲基丁基，3，3-二甲基丁 基，1，1，2-三甲基丙基，1，2，2-三甲基丙基，1-乙基丁基，2-乙基丁 基或1-乙基-2-甲基丙基，优选支链或直链C1-C4-烷基，例如甲基，乙 基，丙基，1-甲基乙基，丁基，1-甲基丙基，2-甲基丙基或1，1-二甲 基乙基，尤其优选甲基。

对于结构单元L中的RL1，RL2，RL3RL4，RL5，RL6，RL7或RL8来说， 支链或直链C2-C6-烯基分别是例如乙烯基，2-丙烯基，2-丁烯基，3- 丁烯基，1-甲基-2-丙烯基，2-甲基-2-丙烯基，2-戊烯基，3-戊烯基， 4-戊烯基，1-甲基-2-丁烯基，2-甲基-2-丁烯基，3-甲基-2-丁烯基， 1-甲基-3-丁烯基，2-甲基-3-丁烯基，3-甲基-3-丁烯基，1，1-二甲 基-2-丙烯基，1，2-二甲基-2-丙烯基，1-乙基-2-丙烯基，2-己烯基， 3-己烯基，4-己烯基，5-己烯基，1-甲基-2-戊烯基，2-甲基-2-戊烯 基，3-甲基-2-戊烯基，4-甲基-2-戊烯基，3-甲基-3-戊烯基，4-甲 基-3-戊烯基，1-甲基-4-戊烯基，2-甲基-4-戊烯基，3-甲基-4-戊烯 基，4-甲基-4-戊烯基，1，1-二甲基-2-丁烯基，1，1-二甲基-3-丁烯 基，1，2-二甲基-2-丁烯基，1，2-二甲基-3-丁烯基，1，3-二甲基-2- 丁烯基，1，3-二甲基-3-丁烯基，2，2-二甲基-3-丁烯基，2，3-二甲基 -2-丁烯基，2，3-二甲基-3-丁烯基，1-乙基-2-丁烯基，1-乙基-3-丁 烯基，2-乙基-2-丁烯基，2-乙基-3-丁烯基，1，1，2-三甲基-2-丙烯 基，1-乙基-1-甲基-2-丙烯基或1-乙基-2-甲基-2-丙烯基。

对于结构单元L中的RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8来说， 支链或直链C2-C6-炔基分别是指，例如乙炔基，2-丙炔基，2-丁炔基，3- 丁炔基，1-甲基-2-丙炔基，2-戊炔基，3-戊炔基，4-戊炔基，1-甲 基-3-丁炔基，2-甲基-3-丁炔基，1-甲基-2-丁炔基，1，1-二甲基-2- 丙炔基，1-乙基-2-丙炔基，2-己炔基，3-己炔基，4-己炔基，5-己 炔基，1-甲基-2-戊炔基，1-甲基-2-戊炔基，1-甲基-3-戊炔基，1- 甲基-4-戊炔基，2-甲基-3-戊炔基，2-甲基-4-戊炔基，3-甲基-4-戊 炔基，4-甲基-2-戊炔基，1，1-二甲基-2-丁炔基，1，1-二甲基-3-丁 炔基，1，2-二甲基-3-丁炔基，2，2-二甲基-3-丁炔基，1-乙基-2-丁 炔基，1-乙基-3-丁炔基，2-乙基-3-丁炔基和1-乙基-1-甲基-2-丙炔 基，优选乙炔基，2-丙炔基，2-丁炔基，1-甲基-2-丙炔基或1-甲基- 2-丁炔基，尤其优选乙炔基。

对于结构单元L中的RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8来说， C3-C7-环烷基分别是指，例如环丙基，环丁基，环戊基，环己基或环 庚基。

支链或直链C1-C6-亚烷基-C3-C7-环烷基，例如由支链或直链C1-C6- 亚烷基和前述的C3-C7-环烷基组成。

对于结构单元L中的RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8来说， 优选的被取代的或不被取代的芳基分别是被取代的或不被取代的苯基， 1-萘基，或2-萘基。

对于结构单元L中的RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8来说， 优选的被取代的或不被取代的芳烷基分别是被取代的或不被取代的苄 基或苯乙基。

对于结构单元L中的RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8来说， 杂芳基分别是指，例如2-吡啶基，3-吡啶基，4-吡啶基，2-呋喃基，3- 呋喃基，2-吡咯基，3-吡咯基，2-噻吩基，3-噻吩基，2-噻唑基，4- 噻唑基，5-噻唑基，2-噁唑基，4-噁唑基，5-噁唑基，2-嘧啶基，4- 嘧啶基，5-嘧啶基，6-嘧啶基，3-吡唑基，4-吡唑基，5-吡唑基，3- 异噻唑基，4-异噻唑基，5-异噻唑基，2-咪唑基，4-咪唑基，5-咪唑 基，3-哒嗪基，4-哒嗪基，5-哒嗪基，6-哒嗪基，3-异噁唑基，4-异 噁唑基，5-异噁唑基，噻二唑基，噁二唑基或三嗪基。

对于结构单元L中的RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8来说， 取代的杂芳基，如上一般性对末端取代的杂芳基所述的那样，还指上 述杂芳基的稠合衍生物，例如吲唑，吲哚，苯并噻吩，苯并呋喃，二 氢吲哚，苯并咪唑，苯并噻唑，苯并噁唑，喹啉，2，3-二氢-1-苯并呋 喃，喃喃并[2，3]吡啶，呋喃并[3，2]吡啶或异喹啉。

对于结构单元L中的RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8来说， 杂芳基烷基是指，例如由C1-C6-亚烷基和如上所述的杂芳基组成的基 团，例如-CH2-2-吡啶基，-CH2-3-吡啶基，-CH2-4-吡啶基，-CH2-2-噻吩 基，-CH2-3-噻吩基，-CH2-2-噻唑基，-CH2-4-噻唑基，CH2-5-噻唑 基，-CH2-CH2-2-吡啶基，-CH2-CH2-3-吡啶基，-CH2-CH2-4-吡啶基，-CH2- CH2-2-噻吩基，-CH2-CH2-3-噻吩基，-CH2-CH2-2-噻唑基，-CH2-CH2-4- 噻唑基，或-CH2-CH2-5-噻唑基。

对于两个基团RL1和RL2或RL3和RL4或RL5和RL6或RL7和RL8来说， 可在各种情况下彼此独立地共同形成3-至7-元、被取代的或不被取代 的、饱和或非饱和的碳环或杂环，该杂环可含有选自O、N或S组的至 多三个杂原子。

-(CH2)w-(YL)y-RL9由C0-C4-亚烷基、任选连接单元YL和RL9组成， YL选自-CO-，-CO-N(RY1)-，-N(RY1)-CO-，-N(RY1)-CO-N(Ry1*)-， -N(RY1)-CO-O-，-O-，-S-，-SO2-，-SO2-N(RY1)-，-SO2-O-，-CO-O-， -O-CO-，-O-CO-N(Ry1)-，-N(RY1)-或-N(RY1)-SO2-，其中

RY1，RY1*

分别是氢，支链或直链的、被取代的或不被取代的C1-C6-烷基-， C1-C6-烷氧基烷基，C2-C6-烯基-，C3-C12-炔基-，CO-C1-C6-烷基-，CO- O-C1-C6-烷基-或SO2-C1-C6-烷基或被取代的或不被取代的C3-C7-环烷 基-，芳基，芳烷基-，CO-O-亚烷基-芳基-，CO-亚烷基-芳基-，CO- 芳基，SO2-芳基-，杂芳基，CO-杂芳基-或SO2-亚烷基-芳基，优选氢 原子，甲基，环丙基，烯丙基或炔丙基，特别优选氢原子或甲基，和

RL9是氢，羟基，CN，卤素，支链或直链、被取代的或不被取代的 C1-C6-烷基，被取代的或不被取代的C3-C7-环烷基，芳基，杂芳基或芳 烷基，被C1-C4-烷基或芳基取代或不被取代的C2-C6-炔基成C2-C6-烯 基，被取代的或不被取代的C6-C12-双环烷基，C1-C6-亚烷基-C6-C12-双 环烷基-，C7-C20-三环烷基或C1-C6-亚烷基-C7-C20-三环烷基，或3-至 8-元、饱和或不饱和杂环，该杂环由至多3个相同或不同的基团取代 并含有至多三个不同或相同的O、N、S杂原子，在此两个基团可能形 成稠合的、饱和的、不饱和的或芳香的碳环或可以含有至多3个不同 或相同的O，N，S杂原子的杂环，该环被取代的或不被取代都是可能的， 或另一被取代的或不被取代的，饱和、不饱和或芳香环可稠合到该环 上，例如，被取代的或不被取代的2-吡啶基，3-吡啶基，4-吡啶基，2- 呋喃基，3-呋喃基，2-吡咯基，3-吡咯基，2-噻吩基，3-噻吩基，2- 噻唑基，4-噻唑基，5-噻唑基，2-噁唑基，4-噁唑基，5-噁唑基，2- 嘧啶基，4-嘧啶基，5-嘧啶基，6-嘧啶基，3-吡唑基，4-吡唑基，5- 吡唑基，3-异噻唑基，4-异噻唑基，5-异噻唑基，2-咪唑基，4-咪唑 基，5-咪唑基，3-哒嗪基，4-哒嗪基，5-哒嗪基，6-哒嗪基，2-(1，3，4- 噻二唑基)，2-(1，3，4)-噁二唑基，3-异噁唑基，4-异噁唑基，5-异噁 唑基或三嗪基。

RL9和Ry1或Ry1*也可能共同形成饱和或不饱和C3-C7-杂环，该杂环 可以不含或含有至多两个另外的选自O、S或N的不同杂原子。

RL9和Ry1或Ry1*优选共同形成环胺作为C3-C7-杂环，这时，基团与 同一氮原子连接，例如N-吡咯烷基，N-哌啶基，N-六氢氮杂基，N- 吗啉基或N-哌嗪基，对于具有游离胺质子的杂环，例如N-哌嗪基，游 离胺质子可以通过常规的胺保护基替换，这些保护基例如是甲基，苄 基，Boc(叔-丁氧基-羰基)，Z(苄氧基羰基)，甲苯磺酰基，-SO2-C1- C4-烷基，-SO2-苯基或-SO2-苄基。

对于结构单元L的RL1，RL3，RL5或RL7来说，优选的-(CH2)w-(YL)y-RL9基是被取代的或不被取代的天然氨基酸侧链，优选被取代的或不被取 代的Ser，Thr，Tyr，Asp，Asn，Glu，Gln，Cys，Met，Lys或Orn 氨基酸侧链，如Bachem公司1999，Novabiochem1999，Neosystem 1997/98和AdvancedChemTech1999的商品目录介绍的非天然氨基酸 侧链，它是被取代或不被取代的。

天然α-氨基酸的侧链是指含有β碳原子的侧链。非天然氨基酸的例 子是β-氨基酸。在这种情形下，侧链是指含有γ碳原子的侧链。取代的 侧链也是指，例如，在侧链的例如-NH2，-SH，-OH或-COOH的官能团 上具有保护基团的侧链。

对结构单元L中的RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8来说特 别优选的基团，每种情况下相互独立地，基团RL1和RL2或RL3和RL4或 RL5和RL6或RL7和RL8之一是氢或甲基。

在结构单元-U-另一优选的实施方案中，基团RL1，RL2，RL3，RL4，RL5， RL6，RL7或RL8相互独立地是氢或甲基，条件是VL或XL相互独立地是 基团-CH(NRL14-SO2-RL15)-，-CH(NRL14-CO-RL16)-，-CH(NRL14-CO-ORL16)-， -CH(NRL14-CO-NRL14’RL15)-，-CH(CO-ORL16)-或-CH(CO-NRL14RL15)-。

对于WL来说，含有至多6个双键和至多6个选自N、O、S杂原子 的被取代的或不被取代的4-至11-元单-或多环脂肪或芳香烃优选为被 取代的或不被取代的亚芳基，例如被取代的或不被取代的亚苯基或亚 萘基，被取代的或不被取代的亚杂芳基，例如基团 和它们的取代或稠合衍生物，或者结构式IWL至IIIWL的基团，

其中的基团可以在两个取向构建入，系数r是0，1，2或3，并且 Z10和Z11相互独立地是CH或氮，Z8和Z8*相互独立地是氧、硫或NH。

WL优选是被取代的或不被取代的亚苯基，基团

或者它们的取代或稠合衍生物，或者化学式IWL至IIIWL基团，

其中的基团可以在两个取向构建入，系数r是0，1，2或3，并且 Z10和Z11相互独立地是CH或氮，Z8和Z8*相互独立地是氧、硫或NH。

对WL来说，结构式IIWL或IIIWL中的Z8优选是氧。

对于VL和XL优选的基团分别是-CO-NRL10-，-NRL10-CO-，-SO2-NRL10-， -NRL10-SO2-，-O-，-CH(NRL14-SO2-RL15)-，-CH(NRL14-CO-RL15)-， -CH(NRL14-CO-ORL16)-，CH(NRL14-CO-NRL14’RL16)-，-CH(CO-RL15)-， -CH(CO-ORL16)-和CH(CO-NRL14RL15)-。

对于VL和XL特别优选的基团分别是-CH(NRL14-SO2-RL15)-， -CH(NRL14-CO-RL15)-，-CH(NRL14-CO-ORL16)-，CH(NRL14-CO-NRL14’RL15)-， -CH(CO-RL15)-，-CH(CO-ORL16)-和CH(CO-NRL14RL15)-。

结构单元L的RL10基团是氢原子，

支链或直链，被取代的或不被取代的C1-C6-烷基，例如如以上对RL1 所述的，优选甲基，

C1-C6-烷氧基烷基，例如甲氧基甲基，乙氧基甲基，叔丁氧基甲基， 甲氧基乙基或乙氧基乙基，

C2-C6-烯基，例如如以上对RL1所述的，优选烯丙基，

C3-C12-炔基，例如2-丙炔基，2-丁炔基，3-丁炔基，1-甲基-2- 丙炔基，2-戊炔基，3-戊炔基，4-戊炔基，1-甲基-3-丁炔基，2-甲 基-3-丁炔基，1-甲基-2-丁炔基，1，1-二甲基-2-丙炔基，1-乙基-2- 丙炔基，2-己炔基，3-己炔基，4-己炔基，5-己炔基，1-甲基-2-戊 炔基，1-甲基-2-戊炔基，1-甲基-3-戊炔基，1-甲基-4-戊炔基，2- 甲基-3-戊炔基，2-甲基-4-戊炔基，3-甲基-4-戊炔基，4-甲基-2-戊 炔基，1，1-二甲基-2-丁炔基，1，1-二甲基-3-丁炔基，1，2-二甲基-3- 丁炔基，2，2-二甲基-3-丁炔基，1-乙基-2-丁炔基，1-乙基-3-丁炔 基，2-乙基-3-丁炔基和1-乙基-1-甲基-2-丙炔基，优选炔丙基，

或CO-C1-C6-烷基，CO-O-C1-C6-烷基-或SO2-C1-C6-烷基，它们在各 种情形下是由相应的CO-，CO-O-或SO2-基团和例如由以上所述的C1- C6-烷基组成，

被取代的或不被取代的C3-C7-环烷基，芳烷基，杂芳基或杂芳基 烷基例如，在每种情况下以上对RL1所述的，

被取代的或不被取代的CO-O-亚烷基-芳基，CO-亚烷基-芳基，CO- 芳基，SO2-芳基，CO-杂芳基，或SO2-亚烷基-芳基，在各种情形下它们 由相应的CO-，CO-O-或SO2基团和例如由如对RL1所述的相应的芳烷基 -，芳基-，杂芳基烷基和杂芳基组成。

此外RL10可以和选自RL1，RL2，RL3，RL4，RL5，RL6，RL7或RL8的一 个基团共同形成被取代的或不被取代的4-至8-元含有至多5个相同或 不同的O、N或S杂原子的杂环。

对于RL10特别优选的基团是氢，甲基，环丙基，烯丙基和炔丙基。

对于RL11或RL12，支链或直链C1-C6-烷基-，C2-C6-烯基-，C2-C6- 炔基-或C1-C6-亚烷基-C3-C7-环烷基或被取代的或不被取代的C3-C7-环 烷基，芳基，芳烷基，杂芳基或杂芳基烷基分别例如是指以上对RL1解 释的相应的基团。

对于RL11或RL12，支链或直链的C1-C4-烷氧基分别是指，例如甲氧 基，乙氧基，丙氧基，1-甲基乙氧基，丁氧基，1-甲基丙氧基，2-甲 基丙氧基或1，1-二甲基乙氧基。

对于RL13，支链或直链的C1-C6-烷基，C2-C6-烯基，C2-C6-炔基或 C1-C6-亚烷基-C3-C7环烷基或被取代的或不被取代的C3-C7-环烷基，芳 基，芳基烷基，杂芳基或杂芳烷基例如是指对RL1的上述相应基团。

对RL14和RL14’来说，优选的基团分别是氢、支链或直链的、被取 代的或不被取代的C1-C6-烷基或C3-C12-炔基或者被取代的或不被取代 的C3-C7-环烷基、芳基、杂芳基或芳烷基。

对RL14和RL14’来说，特别优选的基团分别是氢、甲基、环丙基、 烯丙基或炔丙基。

RL15是如上对RL1所述的支链或直链的、被取代的或不被取代的C1- C6-烷基，优选支链或直链的、被取代的或不被取代的C1-C4-烷基，特 别优选正丁基、2-甲基丙基、1-甲基乙基、

如上对RL10所述的烷氧基烷基、

如上对RL1所述的C1-C6-亚烷基-C3-C7-环烷基，优选-CH2-C3-C7- 环烷基或-CH2-CH2-C3-C7-环烷基，

C6-C12-双环烷基或C7-C20-三环烷基如双环[4.4.0]癸烷基、双环- [2.2.2]-辛烷基、双环[3.2.1]-辛烷基、2，3-二氢化茚基、金刚烷基、 降冰片基、降金刚烷基或樟脑-10-基，

C1-C6-亚烷基-C6-C12-双环烷基或C1-C6-亚烷基-C7-C20-三环烷基如 -CH2-双环[4.4.0]癸烷基、-CH2-双环-[2.2.2]-辛烷基、-CH2-双环- [3.2.1]-辛烷基、-CH2-2，3-二氢化茚基、-CH2-金刚烷基、-CH2-降冰 片基、-CH2-降金刚烷基或-CH2-樟脑-10-基，

如上对RL1所述的C3-C7-环烷基、芳基、芳基烷基或杂芳基烷基， 它们可以被至多三个相同或不同的基团所取代，

或者被至多三个相同或不同的基团所取代的并且含有至多三个相 同或不同的O、N、S杂原子的3-到8-元、饱和的、不饱和的或芳香的 杂环，其中两个基团可能一起形成稠合的、饱和的、不饱和的或芳香 的碳环或含有至多三个相同或不同的O、N、S杂原子的杂环，并且该 环可能被取代或不被取代，或者另一被取代的或不被取代的、饱和的、 不饱和的或芳香的环可稠合在该环上。

此外RL15和RL14或RL14*还可能一起形成任选含有至多两个另外的选 自O、S或N中的杂原子的饱和的或不饱和的杂环。

RL15和RL14或RL14*优选一起形成环状胺基作为C3-C7-杂环，这时基 团与相同的氮原子相连，例如N-吡咯烷基、N-哌啶烷基、N-六氢化氮 杂基、N-吗啉基或N-哌嗪基，对于含有游离胺质子的杂环如N-哌嗪 基，游离胺质子可用常规胺保护基如甲基、苄基、Boc(叔丁氧基-羰基)、 Z(苯甲氧基羰基)、甲苯磺酰基、-SO2-C1-C4-烷基、-SO2-苯基或-SO2- 苄基置换。根据结构单元VL或XL，环状胺基NRL15RL14或NRL15RL14*也可 以是酰胺、氨磺酰、尿烷或其他可能的结构单元的组成部分。

对RL15来说，优选的基团是支链的或直链的、被取代的或不被取 代的C1-C4-烷基或-CH2-C5-C7-环烷基、被取代的或不被取代的C5-C7- 环烷基、苯基、1-萘基、2-萘基、-CH2-萘基、吡啶基、-CH2-吡啶基， 亚乙基苯基，噻吩基，-CH2-噻吩基，噁唑基、-CH2-噁唑基，异噁唑基、 -CH2-异噁唑基、喹啉基、异喹啉基、-CH2-喹啉基、-CH2-异喹啉基、 金刚烷基、-CH2-金刚烷基、降冰片基、-CH2-降冰片基、樟脑-10-基 或-CH2-樟脑-10-基。

对RL16来说，支链的或直链的、被取代的或不被取代的C1-C6-烷基、 烷氧基烷基或C1-C6-亚烷基-C3-C7-环烷基、或被取代的或不被取代的 C3-C7-环烷基、芳基、芳基烷基、杂芳基或杂芳烷基是指例如上述RL15 中提到的相应基团，优选氢、支链的或直链的、被取代的或不被取代 的C1-C4-烷基或-CH2-C5-C7-环烷基、被取代的或不被取代的C5-C7-环 烷基、苯基、1-萘基、2-萘基、-CH2-萘基、苄基、吡啶基、-CH2-吡 啶基、亚乙基苯基、噻吩基、-CH2-噻吩基、噁唑基、-CH2-噁唑基、异 噁唑基、-CH2-异噁唑基、金刚烷基、-CH2-金刚烷基。

对RL16来说，特别优选的基团是支链的或直链的、被取代的或不 被取代的C1-C4-烷基和被取代的或不被取代的苄基。

优选的结构单元L是由至少一个属于结构单元L基团的优选基团 组成，而其他基团可以广泛变化。

特别优选的结构单元L是由结构单元L的优选基团组成。

G是下列结构式IG的结构单元： 其中结构单元G能够在两个取向构建入。

ZG是氧、硫或NRG3，优选氧。

在结构单元G的优选实施方案中，取代模式被固定为通式IGB： 其中结构单元G在这种情况也能够在两个取向构建入。

在结构单元G的特别优选的实施方案中，取代模式被固定为通式 IGB，构建入结构单元G以使结构单元E连接在4位碳原子上并且结构 单元L连接在1位氮原子上。

结构单元G中的RG1和RG2分别是氢、CN、NO2、卤素、支链的或直 链的、被取代的或不被取代的

C1-C6-烷基如被取代的或不被取代的甲基、乙基、丙基、1-甲基 乙基、丁基、1-甲基丙基、2-甲基丙基、1，1-二甲基乙基、戊基、1- 甲基丁基、2-甲基丁基、1，2-二甲基丙基、1，1-二甲基丙基、2，2-二 甲基丙基、1-乙基丙基、己基、1-甲基戊基、1，2-二甲基丁基、1，3- 二甲基丁基、2，3-二甲基丁基、1，1-二甲基丁基、2，2-二甲基丁基、3，3- 二甲基丁基、1，1，2-三甲基丙基、1，2，2-三甲基丙基、1-乙基丁基、2- 乙基丁基或1-乙基-2-甲基丙基，

C2-C6-烯基，如被取代的或不被取代的乙烯基、2-丙烯基、2-丁 烯基、3-丁烯基、1-甲基-2-丙烯基、2-甲基-2-丙烯基、2-戊烯基、3- 戊烯基、4-戊烯基、1-甲基-2-丁烯基、2-甲基-2-丁烯基、3-甲基-2- 丁烯基、1-甲基-3-丁烯基、2-甲基-3-丁烯基、3-甲基-3-丁烯基、1，1- 二甲基-2-丙烯基、1，2-二甲基-2-丙烯基、1-乙基-2-丙烯基、2-己烯 基、3-己烯基、4-己烯基、5-己烯基、1-甲基-2-戊烯基、2-甲基-2- 戊烯基、3-甲基-2-戊烯基、4-甲基-2-戊烯基、3-甲基-3-戊烯基、4- 甲基-3-戊烯基、1-甲基-4-戊烯基、2-甲基-4-戊烯基、3-甲基-4-戊 烯基、4-甲基-4-戊烯基、1，1-二甲基-2-丁烯基、1，1-二甲基-3-丁 烯基、1，2-二甲基-2-丁烯基、1，2-二甲基-3-丁烯基、1，3-二甲基-2- 丁烯基、1，3-二甲基-3-丁烯基、2，2-二甲基-3-丁烯基、2，3-二甲基 -2-丁烯基、2，3-二甲基-3-丁烯基、1-乙基-2-丁烯基、1-乙基-3-丁 烯基、2-乙基-2-丁烯基、2-乙基-3-丁烯基、1，1，2-三甲基-2-丙烯 基、1-乙基-1-甲基-2-丙烯基或1-乙基-2-甲基-2-丙烯基，

C2-C6-炔基，如被取代的或不被取代的乙炔基、2-丙炔基、2-丁 炔基、3-丁炔基、1-甲基-2-丙炔基、2-戊炔基、3-戊炔基、4-戊炔基、 1-甲基-3-丁炔基、2-甲基-3-丁炔基、1-甲基-2-丁炔基、1，1-二甲 基-2-丙炔基、1-乙基-2-丙炔基、2-己炔基、3-己炔基、4-己炔基、5- 己炔基、1-甲基-2-戊炔基、1-甲基-2-戊炔基、1-甲基-3-戊炔基、1- 甲基-4-戊炔基、2-甲基-3-戊炔基、2-甲基-4-戊炔基、3-甲基-4-戊 炔基、4-甲基-2-戊炔基、1，1-二甲基-2-丁炔基、1，1-二甲基-3-丁 炔基、1，2-二甲基-3-丁炔基、2，2-二甲基-3-丁炔基、1-乙基-2-丁 炔基、1-乙基-3-丁炔基、2-乙基-3-丁炔基或1-乙基-1-甲基-2-丙炔 基，

支链的或直链的、被取代的或不被取代的C1-C4-亚烷基-O-RG4、 C1-C4-亚烷基-CO-ORG4、C1-C4-亚烷基-CO-RG4、C1-C4-亚烷基-SO2- NRG5RG6、C1-C4-亚烷基-CO-NRG5RG6、C1-C4-亚烷基-NRG5RG6或C1-C4-亚烷 基-SRG4，它们是由支链的或直链的、被取代的或不被取代C1-C4-亚烷 基例如亚甲基、亚乙基、亚丙基、亚正丁基、亚异丁基或亚叔丁基、 相应的-O-、-CO-、-S-、-N基和以下所述的末端基RG4、RG5和RG6组成，

被取代的或不被取代的

C3-C7-环烷基，如被取代的或不被取代的环丙基、环丁基、环戊基、 环己基或环庚基，

C3-C7-杂环烷基，如被取代的或不被取代的氮杂环丙烷基、二氮杂 环丙烷基、环氧乙基、氧杂氮杂环丙烷基、氧杂环丁烷基、硫杂丙环 基、thietanyl、吡咯烷基、哌嗪基、吗啉基、哌啶基、四氢呋喃基、 四氢吡喃基、1，4-二噁烷基、六氢氮杂基、氧杂环庚三烯基 (oxepanyl)、1，2-氧硫杂戊环基(1，2-oxathiolanyl)或噁唑烷基，

C3-C7-杂环烯基，如被取代的或不被取代的氮杂环丙烯基、二氮杂 环丙烯基、硫杂环丙烯基、thietyl、吡咯啉基、噁唑啉基、氮杂基、 氧杂环庚三烯基(oxepinyl)、α-吡喃基、β-吡喃基、γ-吡喃基、二 羟基吡喃基、2，5-二氢吡咯啉基或4，5-二氢噁唑基，

支链的或直链的、被取代的或不被取代的C1-C4-亚烷基-C3-C7- 环烷基，它们例如由支链的或直链的C1-C4-亚烷基如亚甲基，亚乙基、 亚丙基、亚正丁基、亚异丁基、或亚叔丁基和例如上述C3-C7-环烷基 组成。

支链的或直链的、被取代的或不被取代的C1-C4-亚烷基-C3-C7-杂 环烷基或C1-C4-亚烷基-C3-C7-杂环烯基，它们是由被取代的或不被取 代的C1-C4-亚烷基例如亚甲基、亚乙基、亚丙基、亚正丁基、亚异丁 基或亚叔丁基、以及例如前面所述的C3-C7-杂环烷基或C3-C7-杂环烯 基组成，优选的基团是在环部分含有一个或两个选自N、O或S的杂原 子并且至多两个双键的那些基团，

被取代的或不被取代的

芳基，优选被取代的或不被取代的苯基、1-萘基或2-萘基，

芳烷基，优选被取代的或不被取代的苄基或苯乙基，

杂芳基，优选被取代的或不被取代的2-吡啶基、3-吡啶基、4-吡 啶基、2-呋喃基、3-呋喃基、2-吡咯基、3-吡咯基、2-噻吩基、3-噻 吩基、2-噻唑基、4-噻唑基、5-噻唑基、2-噁唑基、4-噁唑基、5-噁 唑基、2-嘧啶基、4-嘧啶基、5-嘧啶基、6-嘧啶基、3-吡唑基、4-吡 唑基、5-吡唑基、3-异噻唑基、4-异噻唑基、5-异噻唑基、2-咪唑基、 4-咪唑基、5-咪唑基、3-哒嗪基、4-哒嗪基、5-哒嗪基、6-哒嗪基、3- 异噁唑基、4-异噁唑基、5-异噁唑基、噻二唑基、噁二唑基或三嗪基或 其稠合的衍生物，例如吲唑基、吲哚基、苯并噻吩基、苯并呋喃基、 二氢吲哚基、苯并咪唑基、苯并噻唑基、苯并噁唑基、喹啉基或异喹 啉基，

杂芳基烷基，优选被取代的或不被取代的-CH2-2-吡啶基、-CH2-3- 吡啶基、-CH2-4-吡啶基、-CH2-2-噻吩基、-CH2-3-噻吩基、-CH2-2-噻 唑基、-CH2-4-噻唑基、-CH2-5-噻唑基、-CH2-CH2-2-吡啶基、-CH2-CH2-3- 吡啶基、-CH2-CH2-4-吡啶基、-CH2-CH2-2-噻吩基、-CH2-CH2-3-噻吩基、 -CH2-CH2-2-噻唑基、-CH2-CH2-4-噻唑基或-CH2-CH2-5-噻唑基，

或者

基团-S-RG4、-O-RG4、-SO-RG4、-SO2-RG4、-CO-ORG4、-O-CO-RG4、 -O-CO-NRG5RG6、-SO2-NRG5RG6、-CO-NRG5RG6、-NRG5RG6、CO-RG4。

RG1和RG2也可能一起形成被取代的或不被取代的、饱和的或不饱 和的或芳香的3-到9-元碳环、多碳环、含有至多4个选自O、N、S的 杂原子的杂环或杂多环。

对结构单元G中的RG1来说，优选的基团是氢、支链的或直链的、 被取代的或不被取代C1-C6-烷基，优选CF3、C2-C6-烯基、C2-C6-炔基、 C1-C4-亚烷基-ORG4、被取代的或不被取代的芳基、芳烷基、杂芳基或 杂芳烷基或-O-RG4。

对结构单元G中的RG2来说，优选的基团是氢、CN、卤素、支链的 或直链的、被取代的或不被取代C1-C6-烷基，优选CF3、被取代的或不 被取代的C3-C7-环烷基、芳基、芳烷基、杂芳基或杂芳烷基、-SO-RG4、 -SO2-RG4、-CO-ORG4、-SO2-NRG5RG6、-CO-NRG5RG6、-NRG5RG6、CO-RG4、C1- C4-亚烷基-CO-ORG4、C1-C4-亚烷基-SO2-NRG5RG6、C1-C4-亚烷基-CO-NRG5RG6 或C1-C4-亚烷基-NRG5RG6或者被取代的或不被取代的C1-C4-亚烷基-C3- C7-环烷基、C3-C7-杂环烷基、C3-C7-杂环烯基、C1-C4-亚烷基-C3-C7-杂 环烷基或C1-C4-亚烷基-C3-C7-杂环烯基，最后四个基团优选在环部分 含有一个或两个选自N、O或S杂原子和至多两个双键。

结构单元G中的RG2特别优选支链的或直链的、被取代的或不被取 代C1-C6-烷基，被取代的或不被取代的C3-C7-环烷基、芳基、芳烷基、 杂芳基或杂芳烷基、-CO-ORG4、-CO-NRG5RG6、-NRG5RG6、C1-C4-亚烷基- CO-NRG5RG6或C1-C4-亚烷基-NRG5RG6或者被取代的或不被取代的C3-C7- 杂环烷基、C3-C7-杂环烯基、C1-C4-亚烷基-C3-C7-杂环烷基或C1-C4-亚 烷基-C3-C7-杂环烯基，其中最后四个基团优选在环部分含有一个或两 个选自N、O或S杂原子和至多两个双键。

RG3是氢、羟基、CN、支链或直链的、被取代的或不被取代的

C1-C6-烷基，如上述RG1中所描述的，

C1-C4-烷氧基，如上述RL11中所描述的，

被取代的或不被取代的C3-C7-环烷基、芳基或芳烷基，如上述RG1 中所描述的各种情况，

被取代的或不被取代的-O-C3-C7-环烷基、-O-芳基或-O-亚烷基- 芳基，它是例如在每种情况下由-O-基团和上述RG1中所描述的相应基 团所组成，

对于RG4、RG4*、RG5和RG6来说，支链的或直链的、被取代的或 不被取代的C1-C8-烷基分别是例如上面对RG1所提及的C1-C6-烷基以及 庚基和辛基。

对RG4、RG4*、RG5和RG6来说，支链或直链的、被取代的或不被 取代的C1-C8-烷基的优选取代基分别是卤素、羟基、C1-C4-烷氧基、-CN、 -COOH和-CO-O-C1-C4-烷基。

对RG4、RG4*、RG5和RG6来说，支链或直链的、被取代的或不被 取代的C2-C6-烯基、C2-C6-炔基或C1-C4-亚烷基-C3-C7-环烷基、被取 代的或不被取代的C3-C7-环烷基、芳基、芳烷基、杂芳基或杂芳烷基 分别例如是上述RG1中所述的相应基团。

对RG4、RG4*、RG5和RG6来说，优选的支链或直链的、被取代的 或不被取代的-C1-C5-亚烷基-C1-C4-烷氧基分别是甲氧基亚甲基、乙氧 基亚甲基、正丁氧基亚甲基、甲氧基亚乙基或乙氧基亚乙基。

对RG4、RG4*、RG5和RG6来说，优选的支链或直链的、被取代的 或不被取代的单和双烷基氨基亚烷基或酰基氨基亚烷基分别是支链或 直链的、被取代的或不被取代的-C1-C4-亚烷基-NH(C1-C4-烷基)、-C1- C4-亚烷基-N(C1-C4-烷基)2和-C1-C4-亚烷基-NH-CO-C1-C4-烷基。

对RG4、RG4*、RG5和RG6来说，优选的被取代的或不被取代的杂 环烷基、杂环烯基、C1-C4-亚烷基-杂环烷基或C1-C4-亚烷基-杂环烯基 分别是上述RG1中所述的C3-C7-杂环烷基、C3-C7-杂环烯基、C1-C4-亚 烷基-C3-C7-杂环烷基或C1-C4-亚烷基-C3-C7-杂环烯基。

对RG4、RG4*、RG5和RG6来说，特别优选的被取代的或不被取代 的杂环烷基、杂环烯基、C1-C4-亚烷基-杂环烷基或C1-C4-亚烷基-杂环 烯基分别是上述RG1中所述的C3-C7-杂环烷基、C3-C7-杂环烯基、C1-C4- 亚烷基-C3-C7-杂环烷基或C1-C4-亚烷基-C3-C7-杂环烯基，其中在环部 分含有一个或两个选自N、O或S的杂原子至多含有两个双键。

RG5和RG6也可能分别是-SO2-RG4、-CO-O-RG4、-CO-NRG4RG4*或 -CO-RG4，其中RG4*是不同于RG4的RG4基团。

优选的结构单元G是由至少一个属于结构单元G的优选基团、或 者结构单元G的优选取代模式组成，其他基团可以广泛变化。

结构单元G特别优选的是由结构单元G的特别优选的基团组成。

最佳的结构单元G是由结构单元G的优选基团和结构单元G的优 选取代模式组成。

结构单元B是指这样的结构单元，它含有至少一个在生理条件下 作为氢受体能够形成氢键的原子，其中至少一个氢受体原子沿结构单 元骨架沿最短的可能途径与结构单元G之间具有4到13个原子键。结 构单元B的结构骨架的排列可以广泛变化。

在生理条件下，作为氢受体能够形成氢键的适当原子的例子是具 有路易斯碱特性的原子例如杂原子氮、氧或硫。

生理条件是指在有机体部位存在的pH值，在此配体与受体相互作 用。在本发明的情况中，生理条件具有的pH值例如是5到9。

在优选的实施方案中，结构单元B是具有通式IB的结构单元：

A-E-IB 其中A和E具有下列含义： A是选自于下列组的结构单元：

含有至多4个选自O、N或S杂原子的4-至8-元单环饱和的、不饱 和的或芳香烃，其中在各种情况下，可能存在的环氮或碳可能分别被 取代，条件是结构单元A中存在至少一个选自O、N或S的杂原子， 或者

含有至多6个选自O、N或S杂原子的9-至14-元多环饱和的、不 饱和的或芳香烃，其中在各种情况下，可能存在的环氮或碳可能分别 被取代，条件是结构单元A中存在至少一个选自O、N或S的杂原子，

基团： 其中

ZA1是氧、硫或被取代的或不被取代的氮，优选氧或氮，并且

ZA2是被取代的或不被取代的氮、氧或硫，优选氮， 或者基团： 其中

RA18、RA19分别是氢、支链或直链的、被取代的或不被取代的C1-C8- 烷基、C2-C6-烯基、C2-C6-炔基或C1-C5-亚烷基-C1-C4-烷氧基、单或双 烷基氨基亚烷基或酰基氨基亚烷基或被取代的或不被取代的芳基、杂 环烷基、杂环烯基、杂芳基、C3-C7-环烷基、C1-C4-亚烷基-C3-C7-环烷 基、芳烷基、C1-C4-亚烷基-杂环烷基、C1-C4-亚烷基-杂环烯基或杂芳 烷基或者-SO2-RG4、-CO-O-RG4、-CO-NRG4RG4*或-CO-RG4， 并且 E是将结构单元A与结构单元G共价连接的间隔结构单元，其中沿结 构单元骨架E上最短的可能途径的原子键数是3到12。

在特别优选的实施方案中，结构单元A是选自通式IA1到IA19的结 构单元的组：

其中：

m，p，q相互独立地是1，2或3，

RA1、RA2分别是氢、CN、卤素、支链或直链的、被取代的或不被取 代的C1-C6-烷基或CO-C1-C6-烷基或被取代的或不被取代的芳基、芳烷 基、杂芳基、杂芳基烷基或C3-C7-环烷基或-CO-O-RA14、O-RA14、S-RA14、 NRA15RA16、CO-NRA15RA16或SO2NRA15RA16或者RA1和RA2一起是稠合的、被 取代的或不被取代的、5-或6-元、不饱和的或芳香的碳环或杂环，其 中该杂环可以含有至多3个选自O、N或S的杂原子，

RA13、RA13*分别是氢、CN、卤素、支链或直链的、被取代的或不被 取代的C1-C6-烷基或被取代的或不被取代的芳基、芳烷基、杂芳基- C3-C7-环烷基或-CO-O-RA14、O-RA14、S-RA14、NRA15RA16或SO2-NRA15RA16或 CO-NRA15RA16，

其中RA14是氢、支链或直链的、被取代的或不被取代的C1-C6-烷 基、亚烷基-C1-C4-烷氧基、C2-C6-烯基、C2-C6-炔基或C1-C6-亚烷基- C3-C7-环烷基或被取代的或不被取代的C3-C7-环烷基、芳基、芳烷基、 杂芳基或杂芳烷基，

RA15、RA16分别是氢、支链或直链的、被取代的或不被取代的C1-C6- 烷基、CO-C1-C6-烷基、SO2-C1-C6-烷基、COO-C1-C6-烷基、CO-NH-C1-C6- 烷基、芳烷基、COO-亚烷基-芳基、SO2-亚烷基-芳基、CO-NH-亚烷基- 芳基、CO-NH-亚烷基-杂芳基或杂芳烷基或者被取代的或不被取代的 C3-C7-环烷基、芳基、CO-芳基、CO-NH-芳基、SO2-芳基、杂芳基、CO- NH-杂芳基或CO-杂芳基，

RA3、RA4分别是氢、-(CH2)n-(XA)j-RA12或者两个基团一起是3-到8- 元、饱和的或不饱和的或芳香的N杂环，该杂环还可含有两个其他相 同或不同的杂原子O、N或S，该环可能被取代或不被取代，或者另外 一个被取代的或不被取代的饱和的或不饱和的或芳香环可能与该环稠 合，

其中

n是0，1，2或3，

j是0或1，

XA是

-CO-，-CO-N(RX1)-，-N(RX1)-CO-，-N(RX1)-CO-N(RX1*)-，

-N(RX1)-CO-O-，-O-，-S-，-SO2-，-SO2-N(RX1)-，-SO2-O-，

-CO-O-，-O-CO-，-O-CO-N(RX1)-，-N(RX1)-或

-N(RX1)-SO2-，

RA12是氢、支链或直链的、被取代的或不被取代的C1-C6-烷基、被 C1-C4-烷基或芳基取代的或不被取代的C2-C6-炔基或C2-C6-烯基或者被 至多3个相同或不同的基团取代的、3-到6-元、饱和的或不饱和的杂 环，该杂环可含有至多3个相同或不同的杂原子O、N、S，C3-C7-环烷 基、芳基、杂芳基，其中两个基团可能一起形成稠合的、饱和的或不 饱和的或芳香的碳环或杂环，其中杂环可以含有至多3个选自O、N或 S的杂原子，并且该环可能被取代或不被取代，或者另外一个被取代 的或不被取代的饱和的或不饱和的或芳香环可能与该环稠合，或者RA12 能够与RX1或RX1*一起形成饱和的或不饱和的C3-C7-杂环，它任选含有 至多2个另外的选自O、S或N的杂原子，

RX1、RX1*分别是氢、支链或直链的、被取代的或不被取代的C1-C6- 烷基、C1-C6-烷氧基烷基、C2-C6-烯基、C2-C12-炔基、CO-C1-C6-烷基、 CO-O-C1-C6-烷基或SO2-C1-C6-烷基或被取代的或不被取代的C3-C7-环 烷基、芳基、芳烷基、CO-O-亚烷基-芳基、CO-亚烷基-芳基、CO-芳基、 SO2-芳基、杂芳基、CO-杂芳基或SO2-亚烷基-芳基，

RA5是支链或直链的、被取代的或不被取代的C1-C6-烷基、芳烷基、 C3-C7-环烷基或C1-C4-亚烷基-C3-C7-环烷基或者被取代的或不被取代 的芳基、杂芳基、杂环烷基或杂环烯基，

RA6、RA6*是氢、支链或直链的、被取代的或不被取代的C1-C4-烷基、 -CO-O-C1-C4-烷基、芳烷基、-CO-O-亚烷基-芳基、-CO-O-烯丙基、- CO-C1-C4-烷基、-CO-亚烷基-芳基、C3-C7-环烷基或-CO-烯丙基或者在 结构单元IA7中的两个基团RA6和RA6*一起形成被取代的或不被取代的、 饱和的或不饱和的或芳香杂环，除了环氮外，该杂环还可以含有至多 两个另外的不同或相同的杂原子O、N、S，

RA7是氢、-OH、-CN、-CONH2、支链或直链的、被取代的或不被取 代的C1-C4-烷基、C1-C4-烷氧基、C3-C7-环烷基或-O-CO-C1-C4-烷基或 被取代的或不被取代的芳烷基、-O-亚烷基-芳基、-O-CO-芳基、-O-CO- 亚烷基-芳基或-O-CO-烯丙基，或RA6和RA7两个基团一起形成被取代的 或不被取代的、不饱和的或芳香杂环，除了环氮外，该杂环还可以含 有至多两个另外的不同或相同的杂原子O、N、S，

RA8是氢、支链或直链的、被取代的或不被取代的C1-C4-烷基、 CO-C1-C4-烷基、SO2-C1-C4-烷基或CO-O-C1-C4-烷基或被取代的或不被 取代的芳基、CO-芳基、SO2-芳基、CO-O-芳基、CO-亚烷基-芳基、SO2- 亚烷基-芳基、CO-O-亚烷基-芳基或亚烷基-芳基，

RA9、RA10分别是氢、-CN、卤素、支链或直链的、被取代的或不被 取代的C1-C6-烷基或被取代的或不被取代的芳基、芳烷基、杂芳基、 C3-C7-环烷基或-CO-O-RA14、O-RA14、S-RA14、NRA15RA16、SO2-NRA15RA16或 CO-NRA15RA16，或者在结构单元IA14中的两个基团RA9和RA10一起形成5- 到7-元、饱和的或不饱和的或芳香碳环或杂环，它可以含有至多三个 不同或相同的杂原子O、N、S并且被至多三个相同或不同的基团取代 或不被取代，

RA11是氢、-CN、卤素、支链或直链的、被取代的或不被取代的C1-C6- 烷基或被取代的或不被取代的芳基、芳烷基、杂芳基、C3-C7-环烷基或 -CO-O-RA14、O-RA14、S-RA14、NRA15RA16、SO2-NRA15RA16或CO-NRA15RA16，

RA17是氢或者在结构单元IA16中的两个基团RA9和RA17一起形成5- 到7-元、饱和的或不饱和的或芳香杂环，除了环氮外，该杂环还可以 含有至多三个不同或相同的杂原子O、N、S并且被至多三个相同或不 同的基团取代或不被取代，

RA18、RA19分别是氢、支链或直链的、被取代的或不被取代的C1-C8- 烷基、C2-C6-烯基、C2-C6-炔基、C1-C5-亚烷基-C1-C4-烷氧基、单-和 双烷基氨基亚烷基或酰基氨基亚烷基、或被取代的或不被取代的芳基、 杂环烷基、杂环烯基、杂芳基、C3-C7-环烷基、C1-C4-亚烷基-C3-C7-环 烷基、芳烷基、C1-C4-亚烷基-杂环烷基、C1-C4-亚烷基-杂环烯基或杂 芳烷基、或者-SO2-RG4、-CO-O-RG4、-CO-NRG4RG4*或-CO-RG4，

Z1、Z2、Z3、Z4分别是氮、C-H、C-卤素或支链的或直链的、被取 代的或不被取代的C-C1-C4-烷基或C-C1-C4-烷氧基，

Z5是NRA8、氧或硫。

在更优选的实施方案中，结构单元A是通式IA1、IA4、IA7、IA8、IA9、 IA14或IA15的结构单元。

对RA1或RA2来说，支链的或直链的、被取代的或不被取代的C1-C6- 烷基分别是指例如上述对RG1所述的相应基团，优选甲基或三氟甲基。

对结构单元IA1、IA2、IA3或IA17的RA1或RA2来说，支链的或直链 的、被取代的或不被取代的CO-C1-C6-烷基是由例如CO基团和上述对 RA1或RA2所述的支链的或直链的、被取代的或不被取代的C1-C6-烷基 组成。

对RA1或RA2来说，被取代的或不被取代的杂芳基、杂芳烷基、芳 基、芳烷基或C3-C7-环烷基分别是指例如上述对RG1所述的相应基团。

对RA1或RA2来说，被取代的或不被取代的CO-O-RA14、O-RA14、S-RA14、 NRA15RA16、CO-NRA15RA16或SO2-NRA15RA16是由例如基团CO-O、O、S、N、CO-N或SO2-N和以下详细描述的基团RA14、RA15和RA16组成。

RA1和RA2也可能两个一起形成稠合的、被取代的或不被取代的、5- 或6-元不饱和的或芳香碳环或杂环，该杂环可以含有至多三个选自O、 N或S的杂环原子。

RA13和RA13*分别是氢、CN、卤素如氟、氯、溴或碘。

支链的或直链的、被取代的或不被取代的C1-C6-烷基，例如如上 述RG1中所述，优选甲基或三氟甲基或者

被取代的或不被取代的芳基、芳烷基、杂芳基或C3-C7-环烷基或 CO-O-RA14、O-RA14、S-RA14、NRA15RA16、SO2NRA15RA16或CO-NRA15RA16，正如 上述RA1中所述的各种情况。

对RA13和RA13*来说，优选的基团是氢、F、Cl或支链的或直链的、 被取代的或不被取代的C1-C6-烷基、被取代的或不被取代的芳基或芳 烷基或CO-O-RA14、O-RA14、NRA15RA16、SO2-NRA15RA16或CO-NRA15RA16。

对结构单元A中的RA14来说，支链的或直链的、被取代的或不被 取代的C1-C6-烷基、C3-C7-环烷基、亚烷基-环烷基、亚烷基-C1-C4-烷 氧基、C2-C6-烯基或C2-C6-炔基是指例如上述RG1中所述的相应基团。

对结构单元A中的RA14来说，被取代的或不被取代的芳基、芳烷 基、杂芳基或烷基杂芳基是指例如上述RG1中所述的相应基团。

对RA14来说，优选的基团是氢、支链的或直链的、被取代的或不 被取代的C1-C6-烷基和被取代的或不被取代的苄基。

对RA15或RA16来说，支链的或直链的、被取代的或不被取代的C1- C6-烷基或芳烷基或者被取代的或不被取代的C3-C7-环烷基、芳基、杂 芳基或杂芳烷基是分别指例如上述RA14中所述的相应基团。

对RA15或RA16来说，支链的或直链的、被取代的或不被取代的CO- C1-C6-烷基、SO2-C1-C6-烷基、COO-C1-C6-烷基、CO-NH-C1-C6-烷基、COO- 亚烷基-芳基、CO-NH-亚烷基-芳基、CO-NH-亚烷基-杂芳基或SO2-亚 烷基-芳基或者被取代的或不被取代的CO-芳基、SO2-芳基、CO-NH-芳 基、CO-NH-杂芳基或CO-杂芳基是例如由相应的基团-CO-、-SO2-、 -CO-O-、-CO-NH-和相应的上述支链的或直链的、被取代的或不被取代 的C1-C6-烷基、杂芳烷基或芳烷基或者相应的被取代的或不被取代的 芳基或杂芳基组成

对RA3或RA4来说，基团-(CH2)n-(XA)j-RA12分别是指由相应的 -(CH2)n-、(XA)j和RA12基团组成的基团。其中，n是0、1、2或3而j 是0或1。

XA是选自于下组双重键合的基团：-CO-、-CO-N(RX1)-、-N(RX1)-CO-、-N(RX1)-CO-N(RX1*)-、-N(RX1)-CO-O-、-O-、-S-、-SO2-、-SO2-N(RX1)-、-SO2-O-、-CO-O-、-O-CO-、-O-CO-N(RX1)-、-N(RX1)-或 -N(RX1)-SO2-。

RA12是氢、

如RG1中所述的支链的或直链的、被取代的或不被取代的C1-C6-烷 基、

被C1-C4-烷基或芳基取代的或不被取代的C2-C6-炔基或C2-C6-烯 基，例如在上述RL9中所述的、

或者3-到6-元饱和的或不饱和的杂环，该杂环可以被至多三个相 同或不同的基团取代并且可以含有至多3个不同的或相同的杂原子O、 N、S，例如被取代的或不被取代的2-吡啶基、3-吡啶基、4-吡啶基、 2-呋喃基、3-呋喃基、2-吡咯基、3-吡咯基、2-噻吩基、3-噻吩基、2- 噻唑基、4-噻唑基、5-噻唑基、2-噁唑基、4-噁唑基、5-噁唑基、2- 嘧啶基、4-嘧啶基、5-嘧啶基、6-嘧啶基、3-吡唑基、4-吡唑基、5- 吡唑基、3-异噻唑基、4-异噻唑基、5-异噻唑基、2-咪唑基、4-咪唑 基、5-咪唑基、3-哒嗪基、4-哒嗪基、5-哒嗪基、6-哒嗪基、2-(1，3，4- 噻二唑基)、2-(1，3，4)-噁二唑基、3-异噁唑基、4-异噁唑基、5-异 噁唑基或三嗪基。

RA12也可能和RX1或RX1*一起形成饱和的或不饱和的C3-C7-杂环， 该杂环可以含有至多2个其他选自O、S或N中的杂原子。

优选RA12和RX1或RX1*一起形成环状胺基作为C3-C7-杂环，这时基 团与相同的氮原子相连，例如N-吡咯烷基、N-哌啶基、N-六氢化氮杂 基、N-吗啉基或N-哌嗪基，对于含有游离胺质子的杂环如N-哌嗪基， 游离胺质子可用常规胺保护基如甲基、苄基、Boc(叔丁氧基羰基)、Z(苯 甲氧基羰基)、甲苯磺酰基、-SO2-C1-C4-烷基、-SO2-苯基或-SO2-苄基 置换。

对RX1和RX1*来说，支链或直链的、被取代的或不被取代的C1-C6- 烷基、C1-C6-烷氧基烷基、C2-C6-烯基、C2-C12-炔基、CO-C1-C6-烷基、 CO-O-C1-C6-烷基或SO2-C1-C6-烷基或者被取代的或不被取代的C3-C7- 环烷基、芳基、芳烷基、CO-O-亚烷基-芳基、CO-亚烷基-芳基、CO-芳 基、SO2-芳基、杂芳基、CO-杂芳基或SO2-亚烷基-芳基分别是指例如 上述对RL14和RL14*中所述的基团。

对RX1和RX1*来说，优选的基团分别是氢、甲基、环丙基、烯丙基 和炔丙基。

RA3和RA4也可能两个一起形成3-到8-元、饱和的、不饱和的或芳 香N杂环，该杂环还可以含有两个其他相同或不同的选自O、N或S的 杂原子，该环也可能被取代或不被取代或者可能另外一个被取代的或 不被取代的、饱和的或不饱和的或芳香环稠合到该环上。

RA5是支链的或直链的、被取代的或不被取代的C1-C6-烷基、芳烷 基、C1-C4-烷基-C3-C7-环烷基或C3-C7-环烷基或者被取代的或不被取 代的芳基、杂芳基、杂环烷基或杂环烯基，例如上述RG4、RG5和RG6中 所述的基团。

RA6和RA6*分别是氢、支链的或直链的、被取代的或不被取代的

C1-C4-烷基、例如被取代的或不被取代的甲基、乙基、丙基、1- 甲基乙基、丁基、1-甲基丙基、2-甲基丙基或1，1-二甲基乙基，

-CO-O-C1-C4-烷基或-CO-C1-C4-烷基，例如由-CO-O-或-CO-和上述 的C1-C4-烷基组成。

如上述RG1中所述的芳烷基，

-CO-O-亚烷基-芳基或-CO-亚烷基-芳基，例如由-CO-O-或-CO-和 上述的芳烷基组成，

-CO-O-烯丙基或-CO-烯丙基

或者例如上述RG1中所述的C3-C7-环烷基。

此外结构单元IA7中的RA6和RA6*也可能一起形成被取代的或不被 取代的、饱和的或不饱和的或芳香杂环，该杂环中除了环氮外还可以 含有至多2个其他的不同或相同的杂原子O、N、S。

RA7是氢、-OH、-CN、-CONH2、支链的或直链的、被取代的或不被 取代的C1-C4-烷基，例如如上述RA6中所述的，C1-C4-烷氧基、芳烷基 或C3-C7-环烷基，例如如上述RL14中所述的，由-O-CO-和例如上述C1- C4-烷基组成的支链的或直链的、被取代的或不被取代的-O-CO-C1-C4- 烷基，或者由-O-或-O-CO-和上述RG1中所述的相应基团组成的被取代 的或不被取代的-O-亚烷基-芳基、-O-CO-芳基、-O-CO-亚烷基-芳基或 -O-CO-烯丙基。

此外RA6和RA7两个基团可能一起形成被取代的或不被取代的、不 饱和的或芳香杂环，该杂环除了环氮外还可以含有至多两个另外的不 同或相同的杂原子O、N、S。

对结构单元A中的RA8来说，支链的或直链的、被取代的或不被取 代的C1-C4-烷基或被取代的或不被取代的芳基或芳烷基是指例如上述 RA15中所述的相应基团，其中CO-C1-C4-烷基、SO2-C1-C4-烷基、CO-O- C1-C4-烷基、CO-芳基、SO2-芳基、CO-O-芳基、CO-亚烷基-芳基、SO2- 亚烷基-芳基或CO-O-亚烷基-芳基类似于其他组合基团是由CO、SO2或 COO和例如上述对RA15所述的相应的C1-C4-烷基、芳基或芳烷基组成， 这些基团可以被取代或不被取代。

对RA9或RA10来说，在各种情况下的支链的或直链的、被取代的或 不被取代的C1-C6-烷基或被取代的或不被取代的芳基、芳烷基、杂芳 基或C3-C7-环烷基分别是指上述对RA14所述的相应的基团，优选甲基 或三氟甲基。

对RA9或RA10来说，在各种情况下的CO-O-RA14、O-RA14、S-RA14、 SO2-NRA15RA16、NRA15RA16或CO-NRA15RA16分别是指例如上述对RA13所述的 相应的基团。

结构单元IA14中的RA9和RA10两个基团也可能一起形成5-到7-元、 饱和的或不饱和的或芳香碳环或杂环，它可以含有至多三个不同或相 同的杂原子O、N、S并且可以被至多三个相同或不同的基团取代或不 被取代。

在这种情况中，取代基尤其是指卤素、CN、支链的或直链的、被 取代的或不被取代的C1-C4-烷基，例如甲基或三氟甲基或者基团O-RA14、S-RA14、NRA15RA16、CO-NRA15RA16或-((RA8)HN)C＝N-RA7。

对RA11来说，支链的或直链的、被取代的或不被取代的C1-C6-烷 基或被取代的或不被取代的芳基、芳烷基、杂芳基、C3-C7-环烷基或 CO-O-RA14、O-RA14、S-RA14、NRA15RA16、SO2-NRA15RA16或CO-NRA15RA16是指 例如上述对RA9所述的相应的基团。

结构单元IA15中的RA9和RA17两个基团也可能一起形成5-到7-元、 饱和的或不饱和的或芳香杂环，该杂环除了环氮外还可以含有至多三 个不同或相同的杂原子O、N、S并且可以被至多三个相同或不同的基 团取代或不被取代。

对RA18和RA19来说，支链或直链的、被取代的或不被取代的C1-C8- 烷基、C2-C6-烯基、C2-C6-炔基、C1-C5-亚烷基-C1-C4-烷氧基、单-和 双烷基氨基亚烷基或酰基氨基亚烷基或被取代的或不被取代的芳基、 杂环烷基、杂环烯基、杂芳基、C3-C7-环烷基、C1-C4-亚烷基-C3-C7-环 烷基、芳烷基、C1-C4-亚烷基-杂环烷基、C1-C4-亚烷基-杂环烯基或杂 芳烷基或-SO2-RG4、-CO-ORG4、-CO-NRG4RG4*或-CO-RG4分别是指例如上述 对RG5所述的基团，优选氢或支链或直链的、被取代的或不被取代的 C1-C8-烷基。

Z1、Z2、Z3、Z4分别是氮、C-H、C-卤素如，例如C-F、C-Cl、C-Br或C-I或支链或直链的、被取代的或不被取代的C-C1-C4-烷基，它是 由碳基和例如上述对RA6所述C1-C4-烷基组成，或者支链或直链的、被 取代的或不被取代的C-C1-C4-烷氧基，它是由碳基和例如上述对RA7所 述C1-C4-烷氧基组成。

Z5是氧、硫或NRA8。

优选的结构单元A是由至少一个属于结构单元A的基团中的优选 基团组成，而其余的基团可以广泛变化。

特别优选的结构单元A是由结构单元A的优选基团组成。

在优选的实施方案中，分隔结构单元E是指由支链的或直链的、 被取代的或不被取代的并且含有杂原子的脂肪族C2-C30-烃基和/或由4 -到20-元、被取代的或不被取代的和含有杂原子的脂肪族或芳香族 单-或多环烃基组成的结构单元。

在特别优选的实施方案中，间隔结构单元E是具有通式IE的结构单 元：

-(NRE1)i-E1-(UE)h-IE

其中：

UE是氧、硫或NRE2，

h是0或1，

i是0或1，

RE1，RE2分别是氢、支链或直链的、被取代的或不被取代的C1-C6-烷 基、C1-C6-烷氧基烷基、C2-C6-烯基、C2-C12-炔基、CO-C1-C6-烷基、CO- O-C1-C6-烷基、CO-NH-C1-C6-烷氧基烷基、CO-NH-C1-C6-烷基或SO2-C1-C6- 烷基或被取代的或不被取代的杂芳基、芳基烷基、C3-C7-环烷基、CO-O- 亚烷基-芳基、CO-NH-亚烷基-芳基、CO-亚烷基-芳基、CO-芳基、CO-NH- 芳基、SO2-芳基、CO-杂芳基、SO2-亚烷基-芳基、SO2-杂芳基或SO2-亚烷 基-杂芳基，

E1是具有结构式IE1的结构单元： -(CRE3RE4)k1-(LE)k2-(CRE5RE6)k3-(QE)k4-(CRE7RE8)k5-(TE)k6-(CRE9RE10)k7-IE1其中 k2、k4、k6是0或1， k1、k3、k5、k7是0，1或2， RE3、RE4、RE5、RE6、RE7、RE8、RE9、RE10分别是氢、卤素、羟基、支链或直 链的、被取代的或不被取代的C1-C6-烷基、C2-C6-烯基、C2-C6-炔基或亚 烷基-环烷基、-(CH2)X-(YE)ZRE11、被取代的或不被取代的C3-C7-环烷基、 芳基、芳基烷基、杂芳基或杂芳基烷基，或在每种情况下相互独立地， 两个基团RE3和RE4或RE5和RE6或RE7和RE8或RE9和RE10一起是3-7元被取 代的或不被取代的饱和的或不饱和的碳环或杂环，其中杂环可以含有至 多3个选自O、N、S中的杂原子， x是0、1、2、3或4， z是0或1， YE是 -CO-，-CO-N(Ry2)-， -N(Ry2)-CO-， -N(Ry2)-CO-N(Ry2*)-， -N(Ry2)-CO-O-，-O-， -S-，-SO2-， -SO2-N(Ry2)-，-SO2-O-， -CO-O-，-O-CO-， -O-CO-N(Ry2)-， -N(Ry2)-或-N(Ry2)-SO2-， Ry2、Ry2*分别是氢、支链或直链的、被取代的或不被取代的C1-C6-烷基、 C2-C8-炔基、C2-C6-烯基、CO-C1-C6-烷基、CO-O-C1-C6-烷基或SO2-C1-C6- 烷基或被取代的或不被取代的杂芳基、杂芳基烷基、芳烷基、C3-C7-环烷 基、CO-O-亚烷基-芳基、CO-亚烷基-芳基、CO-芳基、SO2-芳基、CO-杂 芳基或SO2-亚烷基-芳基， RE11是氢、羟基、CN、卤素、支链或直链的、被取代的或不被取代的C1-C6- 烷基、被取代的或不被取代的C3-C7-环烷基、芳基、杂芳基或芳基烷基、 被C1-C4-烷基或芳基取代的或不被取代的C2-C6-炔基或C2-C6-烯基、被取 代的或不被取代的C6-C12-双环烷基、C1-C6-亚烷基-C6-C12-双环烷基、C7- C20-三环烷基或C1-C6-亚烷基-C7-C20-三环烷基，或3-到8-元饱和的或不 饱和的杂环，该杂环被至多三个相同的或不同的基团取代并且可以含有 至多三个不同的或相同的O、N、S杂原子，其中两个基团一起可能会形 成稠合的、饱和的、不饱和的或芳香的碳环或杂环，该杂环可含有至多 三个相同的或不同的O、N、S杂原子，并且该环可能被取代或不被取代， 或者另一被取代的或不被取代的、饱和的、或不饱和的或芳香环可与该 环稠合，或者RE11与RY2或RY2*一起形成饱和的或不饱和的C3-C7-杂环， 该杂环可以含有至多两个另外的选自O、S、N的杂原子， LE、TE分别是CO、CO-NRE12、NRE12-CO、硫、SO、SO2、SO2-NRE12、NRE12-SO2、 CS、CS-NRE12、NRE12-CS、CS-O、O-CS、CO-O、O-CO、氧、亚乙炔基、 CRE13-O-CRE14、C(＝CRE13RE14)、CRE13＝CRE14、-CRE13(ORE15)-CHRE14-、 -CHRE13-CRE14(ORE15)-， RE12是氢、支链或直链的、被取代的或不被取代的C1-C6-烷基、C2-C6-烯 基、C2-C8-炔基、被取代的或不被取代的C3-C7-环烷基、杂芳基、芳基烷 基或杂芳基烷基或CO-RE16、COORE16或SO2-RE16， RE13、RE14分别是氢、羟基、支链或直链的、被取代的或不被取代的C1-C6- 烷基、C1-C4-烷氧基、C2-C6-烯基、C2-C6-炔基或亚烷基-环烷基或被取代 的或不被取代的C3-C7-环烷基、芳基、芳基烷基、杂芳基或杂芳基烷基， RE15是氢、支链或直链的、被取代的或不被取代的C1-C6-烷基、C2-C6-烯 基、C2-C6-炔基或亚烷基-环烷基或被取代的或不被取代的C3-C7-环烷基、 芳基、芳基烷基、杂芳基或杂芳基烷基， RE16是氢、羟基、支链或直链的、被取代的或不被取代的C1-C6-烷基、C2- C6-烯基、C2-C6-炔基或C1-C5-亚烷基-C1-C4-烷氧基或被取代的或不被取 代的芳基、杂环烷基、杂环烯基、杂芳基、C3-C7-环烷基、C1-C4-亚烷基- C3-C7-环烷基、芳基烷基、C1-C4-亚烷基-C3-C7-杂环烷基、C1-C4-亚烷基 -C3-C7-杂环烯基或杂芳基烷基并且 QE是被取代的或不被取代的4-到11-元单-或多环脂族或芳香烃，它可以 含有至多6个双键和至多6个相同或不同的选自于N、O、S杂原子，其 中环碳或环氮可能被取代。

在结构单元E中的UE是氧、硫或NRE2，优选硫或NRE2并且特别优选 NRE2。

系数h和i分别是0或1。

在优选的实施方案中，系数i是1。

对结构单元E中的RE1和RE2来说，支链或直链的、被取代的或不被 取代的C1-C6-烷基、C1-C6-烷氧基烷基、C2-C6-烯基、C2-C12-炔基或芳基 烷基或被取代的或不被取代的芳基、杂芳基或C3-C7-环烷基分别是指例如 上述RL14中所述的相应基团。

对RE1和RE2来说，支链或直链的、被取代的或不被取代的CO-C1-C6- 烷基、CO-O-C1-C6-烷基、CO-NH-C1-C6-烷氧基烷基、CO-NH-C1-C6-烷基或 SO2-C1-C6-烷基或被取代的或不被取代的CO-O-亚烷基-芳基、CO-NH-亚烷 基-芳基、CO-亚烷基-芳基、CO-芳基、CO-NH-芳基、SO2-芳基、CO-杂芳 基、SO2-亚烷基-芳基、SO2-杂芳基或SO2-亚烷基-杂芳基分别是由例如相 应的基团CO、COO、CONH或SO2和相应的上述基团组成。

对RE1或RE2来说，优选的基团分别是氢、支链或直链的、被取代的 或不被取代的C1-C6-烷基、C1-C6-烷氧基、C2-C6-烯基、C2-C12-炔基或芳 基烷基或被取代的或不被取代的杂芳基或C3-C7-环烷基。

对RE1或RE2来说，特别优选的基团是氢、甲基、环丙基、烯丙基或 炔丙基。

E1是指具有结构式IE1的结构单元： -(CRE3RE4)k1-(LE)k2-(CRE5RE6)k3-(QE)k4-(CRE7RE8)k5-(TE)k6-(CRE9RE10)k7-IE1其中k2、k4、k6是0或1，并且k1、k3、k5、k7是0，1或2。

对RE3、RE4、RE5、RE6、RE7、RE8、RE9、RE10来说，支链或直链的、被取 代的或不被取代的C1-C6-烷基、C2-C6-烯基、C2-C6-炔基或亚烷基-环烷基 或被取代的或不被取代的C3-C7-环烷基、芳基、芳基烷基、杂芳基或杂芳 基烷基分别是指例如上述RL1中所述的相应基团。

此外，在各种情况下，分别对两个基团RE3和RE4或RE5和RE6或RE7和 RE8或RE9和RE10来说，可以一起形成3-到7-元的、被取代的或不被取代 的饱和的或不饱和的碳环或杂环，其中杂环可以含有至多3个O、N、S中的杂原子。

-(CH2)X-(YE)Z-RE11是由C0-C4-亚烷基、任选的连接单元YE和RE11基团 组成，其中YE选自于-CO-、-CO-N(Ry2)-、-N(Ry2)-CO-、-N(Ry2)-CO-N(Ry2*)-、-N(Ry2)-CO-O-、-O-、-S-、-SO2-、-SO2-N(Ry2)-、-SO2-O-、 -CO-O-、-O-CO-、-O-CO-N(Ry2)-、-N(Ry2)-或-N(Ry2)-SO2-，优选选自于 -CO-N(Ry2)-、-N(Ry2)-CO-、-O-、-SO2-N(Ry2)-、-N(Ry2)-或-N(Ry2)-SO2-， 其中

Ry2和Ry2*分别是氢、支链的或直链的、被取代的或不被取代的C1-C6- 烷基、C2-C6-烯基、C2-C8-炔基、CO-C1-C6-烷基、CO-O-C1-C6-烷基或SO2- C1-C6-烷基或被取代的或不被取代的杂芳基、杂芳基烷基、芳烷基、C3-C7- 环烷基、CO-O-亚烷基-芳基、CO-亚烷基-芳基、CO-芳基、SO2-芳基、CO- 杂芳基或SO2-亚烷基-芳基，优选分别是氢、甲基、环丙基、烯丙基、炔 丙基，并且

RE11是氢、羟基、CN、卤素、支链的或直链的、被取代的或不被取代 的C1-C6-烷基、被取代的或不被取代的C3-C7-环烷基、芳基、杂芳基或芳 基烷基、被C1-C4-烷基或芳基取代的或不被取代的C2-C6-炔基或C2-C6-烯 基，被取代的或不被取代的C6-C12-双环烷基、C1-C6-亚烷基-C6-C12-双环 烷基、C7-C20-三环烷基或C1-C6-亚烷基-C7-C20-三环烷基、或者3-到8-元 饱和的或不饱和杂环，它至多被三个相同的或不同的基团取代并且可含 有至多三个O、N、S杂原子，其中两个基团可能一起形成稠合的、饱和 的或不饱和的或芳香碳环或杂环，该杂环可含有至多3个相同或不同O、 N、S杂原子，该环可能会被取代或不被取代，或者另一被取代的或不被 取代、饱和的、不饱和的或芳香环可能会稠合到该环上，例如被取代的 或不被取代的2-吡啶基、3-吡啶基、4-吡啶基、2-呋喃基、3-呋喃基、2- 吡咯基、3-吡咯基、2-噻吩基、3-噻吩基、2-噻唑基、4-噻唑基、5-噻 唑基、2-噁唑基、4-噁唑基、5-噁唑基、2-嘧啶基、4-嘧啶基、5-嘧啶基、 6-嘧啶基、3-吡唑基、4-吡唑基、5-吡唑基、3-异噻唑基、4-异噻唑基、 5-异噻唑基、2-咪唑基、4-咪唑基、5-咪唑基、3-哒嗪基、4-哒嗪基、5- 哒嗪基、6-哒嗪基、2-(1，3，4-噻二唑基)、2-(1，3，4)-噁二唑基、3-异 噁唑基、4-异噁唑基、5-异噁唑基或三嗪基。

此外RE11和Ry2或Ry2*也可能会一起形成饱和的或不饱和的C3-C7-杂 环，该杂环可以含有至多2个其他选自O、S、N中的杂原子。

优选RE11和Ry2或Ry2*一起形成环状胺作为C3-C7-杂环，在这种情况中， 基团连接到相同的氮原子上，如N-吡咯烷基、N-哌啶基、N-六氢氮杂 基、N-吗啉基或N-哌嗪基，对于含有游离胺质子的杂环例如N-哌嗪基， 游离胺质子可能用常规胺保护基团例如甲基、苄基、Boc(叔丁氧羰基)、 Z(苯甲氧基羰基)、甲苯磺酰基、-SO2-C1-C4-烷基、-SO2-苯基或-SO2-苄 基替换。

对RE3、RE4、RE5、RE6、RE7、RE8、RE9或RE10来说，优选的基团 分别是氢、支链或直链、被取代的或不被取代的C1-C6-烷基、被取代的或 不被取代的芳基或-(CH2)x-(YE)z-RE11基团。

在结构单元E1的优选实施方案中，相互独立地，RE3和RE4或RE5和RE6 或RE7和RE8或RE9和RE10中的一个基团是氢或甲基。

在结构单元E1的特别优选的实施方案中，RE3、RE4、RE5、RE6、RE7、 RE8、RE9或RE10分别是氢或甲基。

LE和TE分别是CO、CO-NRE12、NRE12-CO、硫、SO、SO2、SO2-NRE12、NRE12-SO2、 CS、CS-NRE12、NRE12-CS、CS-O、O-CS、CO-O、O-CO、氧、亚乙炔基、 CRE13-O-CRE14、C(＝CRE13RE14)、CRE13＝CRE14、-CRE13(ORE15)-CHRE14-或 -CHRE13-CRE14(ORE15)-，优选CO-NRE12、NRE12-CO、SO2-NRE12、NRE12-SO2和氧。

RE12是氢、支链的或直链的、被取代的或不被取代的C1-C6-烷基、C2- C6-烯基或C2-C8-炔基或被取代的或不被取代的C3-C7-环烷基、杂芳基、 芳烷基或杂芳烷基，例如在上述RL1各种情况中所描述的，或者CO-RE16、 COORE16或SO2-RE16，优选氢、甲基、烯丙基、炔丙基和环丙基。

对RE13、RE14或RE15来说，支链的或直链的、被取代的或不被取代的 C1-C6-烷基、C2-C6-烯基或C2-C6-炔基或被取代的或不被取代的C3-C7-环 烷基、芳基、芳烷基、杂芳基或杂芳烷基分别指例如在上述RL1中所述的 相应基团。

对RE13或RE14来说，支链的或直链的、被取代的或不被取代的C1-C4- 烷氧基分别指例如上述RA14中所述的C1-C4-烷氧基。

对RE13、RE14或RE15来说，优选的亚烷基-环烷基分别是例如上述RL1 中所述的C1-C4-亚烷基-C3-C7-环烷基。

对RE16来说，支链的或直链的、被取代的或不被取代的C1-C6-烷基、 C2-C6-烯基或C2-C6-炔基或C1-C5-亚烷基-C1-C4-烷氧基，或者被取代的 或不被取代的芳基、杂环烷基、杂环烯基、杂芳基、C3-C7-环烷基、C1-C4- 亚烷基-C3-C7-环烷基、芳基烷基、C1-C4-亚烷基-C3-C7-杂环烷基、C1-C4- 亚烷基-C3-C7-杂环烯基或杂芳烷基是指例如在上述RG4中所述的相应基 团。

对QE来说，被取代的或不被取代的4-到11-元单-或多环脂肪烃或芳 香烃，它可以含有至多6个双键和至多6个选自N、O、S中的相同或不 同杂原子，其中环碳或环氮可能会被取代或不被取代，最好是指被取代 的或不被取代的亚芳基，例如被取代的或不被取代的亚苯基或亚萘基、 被取代的或不被取代的亚杂芳基例如下列基团： 以及它们被取代的或稠合的衍生物，或者通式IE1到IE11的基团： 其中基团可在两个取向构建入。 Z6和Z7相互独立地是CH或氮。 Z8是氧、硫或NH。 Z9是氧、硫或NRE19。 r1，r2，r3和t相互独立地是0，1，2或3。 s和u相互独立地是0、1或2。

QE特别优选被取代的或不被取代的亚苯基，基团： 及其被取代的或稠合的衍生物，或者通式IE1、IE2、IE3、IE4和IE7的基 团，其中基团可在两取向构建入。

RE17和RE18分别是氢、-NO2、-NH2、-CN、-COOH、羟基、卤素、支链 的或直链的、被取代的或不被取代的C1-C6-烷基、C1-C4-烷氧基、C2-C6- 烯基、C2-C6-炔基或亚烷基-环烷基或者被取代的或不被取代的C3-C7-环 烷基、芳基、芳烷基、杂芳基或杂芳基烷基，每种情况下如上文所述。

RE19分别是氢、支链的或直链的、被取代的或不被取代的C1-C6-烷基、 C1-C6-烷氧基烷基、C3-C12-炔基、CO-C1-C6-烷基、CO-O-C1-C6-烷基或 SO2-C1-C6-烷基或被取代的或不被取代的C3-C7-环烷基、芳基、芳烷基、 CO-O-亚烷基-芳基、CO-亚烷基-芳基、CO-芳基、SO2-芳基、杂芳基、CO- 杂芳基或SO2-亚烷基-芳基，优选是氢或支链的或直链的、被取代的或不 被取代的C1-C6-烷基。

优选的结构单元E是由至少一个属于结构单元E的基团的优选基团 组成，而其余基团可以广泛变化。

特别优选的结构单元E是由结构单元E的优选基团组成。

优选的结构单元B或者是由优选的结构单元A组成，而E可以广泛 变化，或者由优选的结构单元E组成，而A可以广泛变化。

通式I的化合物和用来制备它们的中间体可以有一个或多个不对称被 取代的碳原子。该化合物可以是纯对映体或纯的非对映体或其混合物。 优选使用对映体纯化合物作为活性物质。

通式I的化合物也可以其他互变体形式存在。

通式I的化合物也可以为生理上可耐受的盐的形式。

通式I的化合物也可以作为前药以这样一种形式存在，以这种形式通 式I的化合物可以在生理条件下被释放出来。这里可以以结构单元L中 的T基团为例进行说明，在一些情况中它含有能够在生理条件下被水解 成游离羧基的基团。这也适用于在生理条件下能够释放结构单元B或A 的衍生结构单元B或A。

在通式I的优选化合物中，在各种情况下，三个结构单元B、G或L 之一有优选范围，同时其他结构单元可以广泛变化。

在通式I的特别优选的化合物中，在各种情况下，三个结构单元B、 G或L中的两个有优选范围，同时其他结构单元可以广泛变化。

在通式I的非常特别优选的化合物中，在各种情况下，所有三个结构 单元B、G或L都有优选范围，同时其他结构单元可以广泛变化。

例如通式I优选的化合物含有优选的结构单元G，同时结构单元B和 L可以广泛变化。

在通式I特别优选的化合物中，例如B被结构单元A-E-所替代，并 且例如化合物含有优选的结构单元G和优选的结构单元A，同时结构单元 E和L可以广泛变化。

例如，其它特别优选的化合物含有优选的结构单元G和优选的结构单 元A，同时结构单元E和L可以广泛变化。

其中A-E-代表B-的非常特别优选的通式I化合物如下所列，其中在 字母块前的数字是通式I的单个化合物的编号，并且在各种情况下用横 线分开的A-E-G-L字母块中的缩写分别表示单个结构单元A、E、G或L， 并且在表后解释了结构单元缩写。

50pippy-pyma2-imo-bphabs No.A-E-G-L51me2py-pymea-oem-zlys

52imhs-edian2-ocho-psdap 1imhs-m24thizman2-mes-oxal53piraz-dis-ocho-osdap 2dmam-ams2-5pho-zlys54me2py-dis-napo-betaet 3pyr-dimephmep-eoco-psdab55thpym-diphmep-emo-betapy 4imhs-diphmem-baeo-betadcph56thpym-25thiman2-aco-zorn 5imhs-24thizman2-men-zdabs57bzl-m24thizman2-ocho-psdap 6piraz-dis-5pho-aspbzla58bzl-pipa-meo-zdab 7pippy-m24thizman2-eoco-betadcph59tolhs-edian2-chexo-zdapee 82py-eta-nol-psdap60piraz-25oxman2-imo-ibsdap 9bim-pazin-oem-zdapee61bim-amn2-5pho-betapy 10chmhs-dimephmep-5pho-psdap62bimhs-mepazin-meo-aspibua 112py-mepipen2-imo-zdabs632py-pazin-5pho-bsdap 12bimhs-m24thiman2-hso-zdap64amim-ams2-meto-aspibua 13pippy-din-meo-bsdap65bhs-diphmem-emo-bsdap 142py-mepipe-meo-psdab66morhs-pazin-eoco-bhsdab 152py-m25thiz-meo-betapy67phhs-dis-fo-mezphe 16amim-dis-ocho-osdap68am2py-mepipen2-oeto-aspaba 17imhs-dimephmep-5amo-aspbzla69me2py-2pazin-fo-zdab 18me2py-eta-meo-mezphe70chmhs-pipmea-napo-asppha 19bzl-pazin-men-mezphe71piraz-eta2s-5pho-bhsdap 20dpam-mepipe2-sem-nbetabnaphth72pippy-pazi2n-hso-csdap 212py-25oxman2-emo-aspibua73pippy-tetradi-meo-betadcph 222pmhs-din-paco-psdab74am2py-pyma2-5amo-aspbzla 23mam2py-dimephmep-pyo-dfzdap752py-edia2-sem-nbetabnaphth 24mam2py-m24thiz-no2-aspibua76amim-mepipe2-sem-nzdap 25imhs-thizn-men-betadcph77bim-amn3-fo-zlys 26phpip-din-no2-betapy78mam2py-amn2-5amo-bphabs 27tolhs-mepipe-mmen-betadcph79dmam-ams2-cnmo-zdabs 28mam2py-dis-no2-psdab80thpym-mepipe-4amo-zlys 29amim-pazin-meteto-oxal81impy-24thiz-mmen-thizzdap 30bim-pazin-no1-zdap82bhs-edian2-oem-bnsdap 31impy-pyma2-chexo-betainyl834pmhs-edia2-oem-nbetameph 32mam2py-trias-eoco-aspibua84hythpym-24thiz-meo-zlys 33imhs-diphmem-imo-csdap85bhs-pazin-oem-bhsdap 34imhs-props-chexo-bhsdab86piraz-25oxman2-no1-oxal 35ec-diaz-emo-bsdap87im-pipa-ocho-betapy 36mam2py-tetradi-oem-bsdap88im-mea2s-napo-csdap 37imhs-diphmem-5pho-csdap89imhs-amn2-meo-bnsdap 38thpym-mepazin-eoco-asppha902py-tridi-5amo-bsdap 39bimhs-m25thiman2-men-dfzdap91pippy-m24thizman2-oem-bhsdap 40me2py-diphmep-fo-bphabs92im-pnymea-5pho-asppha 41ibhs-pazin-ocho-bphabs93mam2py-m24thizman2-no2-ppsdap 42bhs-pipmea-ocho-tsdap94chmhs-thizn-napo-psdapee 43morhs-diphmem-cnmo-betadcph95amim-diphmep-5amo-bhsdap 44ppy-dimen-oem-betainyl96amim-amn3-napo-betainyl 45impy-din-no1-aspibua97morhs-amn3-ocho-zlys 46menim-ams2-eoco-zdab98am2py-tetradi-eoco-zdabs 47mam2py-amo3-baeo-glupha99amim-25thizman2-napo-aspbzla 48bhs-edian2-no2-psdab100bim-m24oxman2-mmen-zdabs 49am4py-am2-sem-nbeta34dimeoph101imhs-24thizman2-emo-asppha 102bim-25oxman2-mecpo-glyzdap154imhs-pazin-ocho-bsdap 103thpym-mepipe-meo-zdap155dmam-pipa-mecpo-betainyl 104mam2py-pyma2-meto-bhsdab156me2py-24thiz-oem-betapy 105am-25thizman2-napo-zdab157bim-pyma2-mes-dfzdap 106piraz-24thiz-baeo-psdab158mam2py-pipmeo-5amo-bhsdab 107ibhs-propa2s-5amo-glubzla159amim-am3diaz-cnmo-aspbzla 108cl3pyme-diphmem-chexo-betaet160am2py-amn3-oem-ppsdap 1092py-edian2-eoco-bnsdap161edothpym-dis-meto-bphabs 110prhs-dimephmep-no2-zdap162amthiaz-dimephmem-eoco- 111amthiaz-pipmea-emo-glyzdapbetainyl 112me2py-mepipe-eoco-bnsdap1632py-m25thiz-mes-aspbzla 113amim-diphmem-meo-bhsdab164piraz-trias-napo-zdab 114dmam-amn3-mes-betainyl165mepip-pymea-no1-psdab 115piraz-dimephmep-ocho-zlys166pippy-tridi-no2-betadcph 116im-2pazin-mes-bphabs167bhs-edian2-no2-bhsdap 117impy-ams2-napo-tsdap168pyraz-din-meo-betapy 118piraz-pipa-5amo-betaet169pyraz-dimen-paco-bsdap 119bzl-edia2-oem-npsdap170chhs-mepipe-fo-mezphe 120bhs-mepipe-no2-psdap171hythpym-tetradi-ocho-betainyl 121hythpym-24thiman-napo-aspibua172dhim-24thizman2-pro-bnsdap 122hythpym-dich-mes-psdab173me2py-amn3-napo-aspbzla 123gua-24thizman2-imo-aspibua174am2py-mepipe-5pho-bnsdap 124imhs-din-pro-csdap175amim-ams2-no2-betapy 125bhs-pymea-meo-aspibua176mam2py-dich-oem-betapy 126me2py-24thiz-fo-bhsdap177imhs-25thiz-pheo-glyzdap 127dhim-eta-emo-betapy178thpym-amn2-mes-zdab 128hythpym-am3-sem-nzdab179nmhs-amn2-mmen-asppha 129phhs-dimephmep-oem-tsdap180dmam-tetradi-imo-glubzla 130bim-tetradi-chexo-zlys181me2py-24thizman2-ocho-bhsdap 131bimhs-pnymea-ocho-zdap182bhs-pazin-ocho-zdab 132thpym-dimephmem-men-betaet183dmbim-pnymea-no2-mezphe 133bhs-dimen-chexo-betadcph184hythpym-pnymea-5pho-csdap 134imhs-n2nme2n-hso-zlys185dhim-pnymea-meto-zlys 1352pmhs-am2-oem-nbeta34dimeoph186bim-tetradi-cpro-osdap 136deam-dis-5amo-aspibua187cl3pyme-mepipen2-meo-aspbzla 137bhs-edian2-no2-bphabs188am4py-pentadi-mes-zdapee 1382py-mepipe-eoco-zdap189impy-m25thiz-mes-zdab 139me2py-m24oxman2-5amo-bphabs190prhs-thizo-aco-betadcph 140impy-mepazin-emo-betaet191piraz-m25thiz-oem-bsdap 141tolhs-edia2-sem-nbeta34dimeoph192pippy-n2o2n-mmen-psdap 142bim-eta-no2-psdap193tolhs-amo2-meo-glupha 143im-pipmes-cpeo-zdap194impy-butn-pheo-csdap 144pyraz-n2o2n-ocho-aspibua195thpym-25oxman2-men-aspibua 145amim-pipa-mecpo-zdap196bim-edian2-mes-bnsdap 146bhs-am2-oem-npsdap197amim-tetradi-eoco-aspbzla 147deam-edian2-mes-psdap198tolhs-m25oxman2-4amo-aspbzla 148me2py-eta2s-meo-bhsdab199im-m24thiman2-chexo-zdap 149bimhs-25thiz-cpro-aspibua200me2py-amo2-mes-bhsdap 150hythpym-amn3-eoco-asppha201am2py-mepipen2-5pho-psdab 151bhs-tetradi-4amo-zdabs202piraz-edian2-eoco-zdap 1522py-dimephmem-chexo-glyzdap203dhim-pipa-meo-aspibua 153bimhs-ams2-imo-ibsdap204ec-eta2s-ocho-glyzdap 205hythpym-am3-sem-nzdab257bhs-thizn-cno-bsdap 206pippy-24oxman2-imo-bhsdap258amim-tetradi-napo-aspaba 207pippy-24thizman2-emo-betadcph259am4py-din-oem-zdap 208bzl-din-fo-betapy260deam-24thiz-cpro-mezphe 209imhs-diphmep-men-asppha261thpym-pazin-eoco-bsdap 210thpym-edian2-no1-psdab262piraz-pyma2-no2-bhsdap 211impy-mepipen2-napo-glupha263me2py-24thiman2-meo-bhsdab 212moegua-mepipe-pro-bhsdab2642py-mepazin-mes-psdab 213hythpym-amn3-chexo-bhsdab265mam2py-mepipe2-oem-nbetapy 214piraz-eta-no1-betapy266imhs-24thiman-fo-betapy 215imhs-ams2-eoco-csdap267bim-eta-mes-betapy 216hythpym-mepipe-aco-aval268bim-24thiz-meto-bhsdap 217bim-amn2-no1-zdap269thpym-pazin-no2-zdab 218bzl-pnymea-imo-bhsdap270mam2py-dimephmep-mes-betadcph 219thpym-edian2-ocho-psdab2712py-amn3-men-glyzdap 220bhs-m24thizman2-5amo-csdap272bimhs-diaz-no2-zdapee 221bz-dimephmem-4pho-aval273pippy-amn3-men-psdab 222dhim-25thiz-hso-aspibua274impy-pyma2-imo-aspibua 2232py-edian2-eoco-bsdap275bimhs-pipmeo-fo-bhsdap 224thpym-pazin-no1-betapy276am4py-tridi-daco-ibsdap 225bhs-m24thiz-daco-mezphe277thpym-mepipe-ocho-zdab 226bim-edian2-meo-zdab278hythpym-eta2s-5pho-dfzdap 227emnim-pymea-mes-bphabs279chmhs-amn2-men-mezphe 228impy-mea-meo-ibsdap280thpym-pipa-4pho-zdap 229impy-dimen-mes-mezphe281pippy-pymea-4pho-betapy 230imhs-amn2-mes-zdab282thpym-mepipe-ocho-glupha 231piraz-diaz-cno-betainyl283impy-24thizman2-mes-mezphe 232impy-m24thizman2-emo-bsdap284bimhs-tridi-eoco-aspibua 233amim-24thiz-meo-bhsdap285bimhs-dis-mes-bphabs 234am2py-mepipe-5amo-bnsdap286bhs-am3diaz-5amo-mezphe 235amim-trias-paco-psdap287cl3pyme-amn3-daco-psdapee 236imhs-edian2-mes-bsdap288bhs-pipmea-cpro-asppha 237bim-dis-emo-asppha289amim-pnymea-oem-bhsdap 238bim-24thiman2-5pho-aspibua290bhs-edian2-no2-zdab 239bhs-edian2-oem-psdab291bz-eta-emo-aspbzla 2402py-pyma2-chexo-psdapee292dpam-dio-eoco-bhsdab 241emnim-am2-oem-nbeta34dimeoph293imhs-24thizman2-cno-aspibua 242pippy-m25thiz-meo-dfzdap294piraz-trias-meo-zlys 243am2py-amo2-napo-bhsdap295ibhs-pipa-meto-csdap 244deam-am3-oem-npsdap296ec-am3diaz-ocho-dfzdap 2452pmhs-pymea-ocho-bhsdap297bhs-mepazin-meo-betadcph 246thpym-dipch-chexo-glyzdap298pyraz-pipmea-mes-psdap 247bim-mepipe-ocho-betapy299me2py-amo2-mes-asppha 248dhim-pipa-aco-zdabs300tolhs-am2-sem-nbeta34dimeoph 249am2py-ams2-5pho-zdap301bhs-amn3-imo-osdap 250bim-propn-eoco-aspibua302n2py-dimephmem-pro-betainyl 251imhs-ams2-men-aspbzla303bhs-trias-napo-dfzdap 252piraz-pymea-chexo-csdap304thpym-dimen-men-dfzdap 253tolhs-mepazin-oeto-zdab305thpym-thizn-cpeo-ibsdap 254bim-diphmep-5amo-bsdap306imhs-eta-chexo-tsdap 255bimhs-propa2s-cpeo-csdap307piraz-thizn-paco-glyzdap 256thpym-pazin-no2-bhsdap308pyraz-diphmep-5amo-aval 309piraz-pyma2-napo-betadcph361dmbim-eta-fo-asppha 3102py-pipmea-eoco-zdap362amim-amn2-mes-thizzdap 311bhs-mepipe-meo-psdab363mepip-pazi2n-5pho-betapy 312piraz-trias-emo-bhsdap364bim-mepipe-oem-bnsdap 313amim-edia2-oem-nbeta34dimeoph365imhs-eta-5pho-zdab 314nmor-mepazin-no1-bhsdab366me2py-am3-oem-npsdap 315impy-mepipe-chexo-bphabs367pippy-tetradi-imo-glyzdap 316dmam-am3diaz-no1-glyzdap368thpym-m24thizman2-oem-dfzdap 317bim-mepipe-meo-bsdap369piraz-pipmea-cpro-betapy 318piraz-mepazin-chexo-psdap370deam-mepipe-cpeo-bnsdap 319moegua-mepazin-fo-csdap371dhim-25oxman2-napo-psdab 320imhs-25thiman2-eoco-bphabs372amim-n2nme2n-5amo-bsdap 321me2py-m25thiz-chexo-zorn373prhs-24thizman2-mommo-csdap 322mam2py-tridi-men-mezphe3742py-edia2-oem-nbetapy 323morhs-am3-oem-nbetameph375bimhs-din-meo-bhsdab 324pyrhs-m25thiz-oem-glupha376chhs-pyma2-ocho-betapy 325me2py-pnymea-mes-betainyl3772py-amn3-5pho-psdab 326mam2py-amo2-no1-zdab378thpym-eta-5pho-bhsdap 3272py-mepipe-mes-bsdap379piraz-pyma2-meo-psdab 328impy-diphmep-ocho-asppha380chhs-thizn-fo-betainyl 329nmor-hexas-chexo-psdap381pippy-m25thiz-chexo-zorn 330me2py-pipmea-ocho-asppha382fthpym-pnymea-oem-bnsdap 331imhs-pazin-no1-psdap383bhs-24thizman2-no2-bphabs 3322py-mepipe-5pho-zdab384pippy-edian2-chexo-psdab 333fthpym-am3-sem-nbetabnaphth385imhs-amn2-no2-betapy 334bhs-amn2-oem-psdap3862py-25thiz-no1-aval 335piraz-pazi2n-ocho-aspibua387impy-pymea-peo-aspbzla 336emnim-24thizman2-imo-bhsdab388pyraz-tridi-cpro-bphabs 337nim-diphmem-oem-zdab389me2py-din-imo-bhsdab 3382py-ms-mes-zdap390phhs-hexadi-5amo-psdap 3392py-edian2-ocho-bsdap391mepip-m25thiz-ocho-zdabs 340nmor-diphmep-no1-bsdap392imhs-amn2-5pho-bhsdap 341amim-25oxman2-nmo-betadcph393bhs-m25thiz-fo-ppsdap 342mam2py-edian2-5pho-osdap394dhim-edian2-imo-bsdap 343pyr-n2o2n-cno-betapy395me2py-dimen-aco-zorn 344phpip-pipmes-fo-mezphe3962py-eta-oem-zdapee 345bhs-24thiz-mes-psdab397cl3pyme-25oxman2-5amo-bphabs 346fthpym-eta-mes-dfzdap398phpip-edian2-fo-psdap 347bhs-edian2-ocho-psdap399am2py-trias-oem-psdapee 348ibhs-mepipe-emo-bhsdap400nmhs-3pazin-imo-dfzdap 349edothpym-pipa-pro-zdap401thpym-dimen-napo-bhsdab 350bzl-am2-sem-npsdap402amim-24thizman2-meo-psdab 351pippy-dimephmep-emo-bphabs403bim-dipch-eoco-zdabs 352mam2py-pipmea-napo-bnsdap404ppy-m25thiz-no1-aspbzla 353me2py-dimephmem-mes-betapy405ec-eta-meo-aspibua 354imhs-24thizman2-no2-asppha406thpym-pipa-oeto-mezphe 355am4py-n2nme2n-no2-bhsdap4072py-tetras-no2-csdap 356mam2py-tetradi-no2-dfzdap4082py-25oxman2-cno-psdap 357imhs-dis-meo-zdabs409chhs-pipmeo-oem-betadcph 358bimhs-propa2s-oem-asppha410bzl-eta-fo-mezphe 359chmhs-24thiz-napo-glyzdap411bim-pazin-no1-bnsdap 360me2py-edian2-5amo-aspbzla412nim-am3-oem-nzdab 413bim-dimen-eoco-zdabs464bhs-pazin-no1-bhsdap 414bhs-amn2-5pho-zdab465thpym-mepipe-5pho-bsdap 415mepip-pymea-emo-zdap4662py-pnymea-ocho-aspbzla 416am2py-pipmea-fo-zdab467pyraz-pazin-fo-aspbzla 417hythpym-diphmem-pheo-zdap468nmor-pymea-men-zdabs 418piraz-ams2-5pho-zdabs469gua-amo3-oeto-mezphe 419impy-edia2-sem-nbetabnaphth470bzl-mepazin-hso-aspibua 420thpym-eta-meo-mezphe471amim-mepazin-baeo-zdab 421prhs-m25thiz-meo-dfzdap472mam2py-24thizman2-cno-glubzla 422bhs-pazin-mes-zdab473bimhs-amn3-ocho-aspbzla 423am2py-thizn-4amo-bphabs474hythpym-dimephmep-no2-csdap 424am2py-dio-no1-psdap475pippy-pipa-cno-mezphe 425gua-mepipen2-no2-thizzdap476dhim-pymea-mecpo-aval 426am-dimen-5pho-glubzla477piraz-pnymea-oem-glyzdap 427nim-amn3-paco-zdabs4782py-amn2-ocho-bhsdap 428moegua-eta-chexo-bhsdab479ibhs-24thiz-meteto-bsdap 429dhim-pymea-chexo-zdabs480cl3pyme-am2-sem-nbeta34dimeoph 430amim-edia2-sem-nbetameph481phhs-edian2-fo-zdap 431piraz-pazin-baeo-aspbzla482nim-m24thizman2-men-osdap 432nmhs-24thizman2-5amo-bhsdap483dhim-dimen-imo-csdap 433bim-dis-imo-betainyl484bim-din-emo-zdap 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453amim-edian2-5pho-betapy504me2py-mepipe-4amo-betainyl 454hythpym-m25thiman2-chexo-505mam2py-m25thiz-imo-psdap

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1448pippy-am3-sem-nzdap1500bim-propn-nmo-bhsdab 1449mam2py-dimephmem-fo-betainyl1501bhs-mepipe-napo-ibsdap 14502py-dimephmem-oem-zdab1502thpym-mepipe2-oem-nzdap 1451me2py-tetradi-pyo-psdapee15032py-3pazin-4amo-psdab 1452bhs-mepazin-mes-bnsdap1504imhs-pipa-meo-betapy 1453imhs-ms-fo-csdap1505chhs-pipa-no2-zdap 1454imhs-pazi2n-chexo-tsdap1506hythpym-thizn-meo-psdab 1455pippy-diphmep-emo-bnsdap1507me-pnymea-emo-bnsdap 1456bhs-pnymea-oem-bhsdab1508menim-dimephmem-meto-zdabs 1457deam-m25thiz-chexo-asppha1509bimhs-mepipen2-cpeo-zorn 1458hythpym-3pazin-imo-zdab1510bhs-pazin-pyo-asppha 1459thpym-diphmem-napo-csdap1511chhs-pazin-oem-betapy 1460pippy-diphmem-chexo-zdab1512bim-pazin-ocho-bhsdap 1461ppy-thizn-ocho-glyzdap1513imhs-m24thizman2-cnmo-asppha 1462dhim-pipa-oem-psdap15142py-edian2-oem-psdab 1463imhs-ams2-no1-zdab1515imhs-tetradi-mmen-zdabs 1464bim-mepipe-no2-psdap15162py-edian2-no2-psdap 1465chmhs-dis-imo-aspbzla1517dmam-dimephmem-men-bhsdap 1466bim-mea2s-meo-oxal1518am2py-24thiz-mes-bphabs 1467bz-25thizman2-mmen-asppha1519imhs-amn2-no2-bhsdap 1468dhim-mepipe-5amo-bphabs1520pyr-dis-aco-bhsdap 1469bhs-pazin-ocho-psdab1521chmhs-pymea-daco-aspibua 1470amim-dimephmep-5amo-bhsdap1522impy-ams2-men-aspbzla 1471tolhs-diphmem-no1-zlys1523morhs-pyma2-no2-zdabs 1472imhs-pipmeo-fo-aspbzla1524im-24thiz-fo-zdabs 1473phhs-dimephmem-baeo-dfzdap1525hythpym-tetradi-cpro-betadcph 1474hythpym-3diaz-paco-aval15262py-eta-oem-betapy 14752py-pentas-ocho-bhsdab1527piraz-thizn-baeo-bphabs 1476me-n24thiman-fo-dfzdap1528bim-amo3-oem-aval 1477pyr-25oxman2-5amo-bnsdap1529npip-mea2s-chexo-betapy 1478thpym-trias-5pho-ibsdap1530bim-diphmep-meo-bphabs 1479bim-amn3-no2-psdab1531bz-mepipe2-oem-nzdap 1480dmthpym-dipch-imo-aspibua15322py-pyma2-eoco-asppha 1481chhs-24thiz-fo-aspibua1533bim-dimephmep-emo-asppha 1482dhim-diphmem-no2-zdap1534am2py-amn2-5pho-csdap 1483me2py-n24thiman-5amo-psdap1535mam2py-24thiman-napo-zdap 1484am-dimephmep-chexo-asppha1536pippy-diphmem-oem-betadcph 1485imhs-thizo-emo-glubzla1537impy-amo2-5pho-betadcph 1486prhs-tridi-napo-zdabs1538bimhs-am2-sem-nbetapy 14872py-edian2-5pho-psdap1539imhs-2pazin-aco-mezphe 1488n2py-am3-oem-nzdab1540dhim-amo2-ocho-aspbzla 1489cl3pyme-eta-no1-bphabs1541bim-m24thizman2-eoco-betapy 1490ibhs-pymea-oem-zdab1542ec-eta-imo-psdab 1491thpym-amn2-mes-bhsdap1543dmbim-am3-oem-nzdab 1492thpym-24thiz-no2-tsdap1544cl3pyme-amn2-mes-zdab 1493pyr-24thizman2-eoco-betainyl1545dpam-amn2-emo-dfzdap 1494bim-edian2-meo-betapy1546bhs-edian2-napo-bhsdab 1495piraz-propn-chexo-aspbzla1547pyrhs-ms-oem-zdab 1496dmthpym-am3-sem-nzdap1548im-mepazin-baeo-ppsdap 1549pippy-ams2-emo-psdap1601pyr-dimephmep-no1-bsdap 1550imhs-pazin-mes-bsdap1602amim-butn-4amo-glyzdap 1551hythpym-m25thiz-emo-bsdap1603bim-dimen-emo-glubzla 1552phpip-pipa-eoco-csdap1604impy-propa2s-ocho-dfzdap 1553mam2py-pazi2n-no1-asppha1605dhim-amn3-men-bphabs 1554bimhs-dich-meo-zdab1606mam2py-dis-emo-glyzdap 1555z-tridi-eoco-betapy1607impy-dimephmem-ocho-zdabs 1556z-am3-oem-nzdab1608am2py-m24thizman2-emo-bhsdap 15572py-pnymea-oem-zdab1609bhs-pyma2-no2-bnsdap 1558thpym-eta-mes-psdab1610me2py-diphmep-ocho-mezphe 1559hythpym-mepipe-oem-betainyl1611bimhs-propa2s-mecpo-bhsdap 1560am2py-propn-mes-bsdap1612hythpym-mepipe2-sem-nbeta- 1561am2py-ams2-paco-bhsdab34dimeoph 1562imhs-amn2-meo-bsdap1613bimhs-pentadi-napo-aspibua 1563bhs-edia2-sem-nbetapy1614thpym-mepipe-eoco-psdap 1564moegua-dis-meo-csdap1615gua-tetras-emo-bphabs 1565pyr-tetradi-mommo-dfzdap1616thpym-am2-oem-nbetapy 15662py-pnymea-no1-glyzdap1617emnim-mepipen2-eoco-zdabs 1567n2py-edian2-men-bphabs1618pippy-m25thiman2-eoco-bphabs 1568me2py-pentadi-meo-zdap1619tolhs-dich-imo-oxal 1569cl3pyme-pipmea-no2-dfzdap1620dmbim-edian2-men-bhsdap 15702py-dis-meo-bhsdab1621bimhs-dimephmem-no1-zdab 1571me2py-m24thizman2-oeto-psdab1622bhs-hexadi-fo-glyzdap 1572bim-diphmem-chexo-asppha1623hythpym-pymea-napo-bsdap 1573pippy-pymea-5pho-glyzdap1624pippy-mepipe2-oem-nbetapy 1574pippy-trias-no2-betainyl1625npip-edia2-oem-nbetabnaphth 1575edothpym-eta-napo-aspbzla1626bimhs-edian2-cpeo-bhsdap 1576dmbim-pipmeo-emo-zdab1627dmbim-tetradi-men-bhsdab 1577bim-pazin-ocho-bsdap1628pippy-24thiman2-eoco-bhsdap 15782py-n2nme2n-napo-aspibua1629bzl-m25oxman2-cnmo-dfzdap 1579impy-mepazin-napo-bhsdab1630pippy-pipmes-cnmo-psdap 1580thpym-diaz-meo-bnsdap1631im-n2nme2n-no2-bsdap 1581bim-edia2-oem-npsdap1632bim-thizn-no1-bsdap 1582dhim-dimephmem-hso-asppha1633thpym-2pazin-meo-mezphe 1583npip-mepazin-pro-bphabs1634tolhs-pipa-eoco-bnsdap 1584thpym-eta-eoco-aspbzla1635impy-dich-ocho-betaet 1585imhs-24thizman2-mommo-aval1636imhs-emn2-meo-betapy 1586am2py-edian2-aco-psdab1637ibhs-mepipe-5pho-betadcph 1587bimhs-amn3-mecpo-glyzdap1638me-eta2s-no1-aspbzla 1588mam2py-dimephmem-cpro-bphabs16392py-mepipe-meo-zdab 1589bim-diphmep-ocho-psdap1640am2py-amo2-fo-psdapee 1590ppy-diphmem-eoco-bnsdap1641ibhs-edian2-eoco-csdap 15912py-mepipen2-daco-bphabs1642me-amo2-eoco-zdap 1592dmam-amo3-cnmo-bhsdab1643bhs-mepipe-ocho-zdap 1593imhs-eta-cnmo-betainyl1644bim-tetras-meteto-tsdap 1594pyraz-hexadi-eoco-bnsdap1645nmhs-dimephmep-napo-psdap 1595pippy-24thiz-oeto-glyzdap1646amim-mepipen2-meo-psdab 15962pmhs-mepipe-fo-psdab1647bim-amn2-oem-betapy 1597nim-pipmea-mes-betapy1648mepip-dis-napo-zdabs 1598phhs-n2nme2n-ocho-zdap1649bim-mepazin-meo-aspibua 1599dmthpym-edian2-mes-bphabs1650npip-pymea-men-bphabs 1600pippy-3diaz-emo-betadcph1651mam2py-tridi-ocho-betainyl 1652ec-m25thizman2-meto-glyzdap1702bim-diphmep-mecpo-bhsdab 1653am2py-pazin-fo-zlys1703amim-tetradi-fo-zorn 1654hythpym-24thiz-no2-asppha1704thpym-tetradi-eoco-bhsdap 1655imhs-eta-eoco-bsdap1705morhs-diphmem-imo-zdab 1656dhim-mea2s-men-tsdap1706ppy-m25thiman2-pyo-betadcph 1657am2py-tetradi-5amo-psdap1707imhs-pazin-fo-csdap 1658bhs-amn3-napo-glyzdap1708morhs-pipmea-5amo-asppha 1659thpym-din-fo-bhsdap1709am2py-diphmep-cno-zdabs 1660am2py-mepipe2-oem-nbetameph1710thpym-m25thiz-4pho-ppsdap 1661hythpym-24thiman2-napo-1711imhs-amn2-no2-zdab

aspbzla1712bhs-amn2-ocho-bhsdap 1662me2py-m25thiz-eoco-bphabs1713bimhs-propa2s-peo-mezphe 1663dpam-m25thiz-oeto-zdap1714thpym-pipmea-5pho-aspibua 1664edothpym-pentas-fo-aspbzla1715dhim-25thizman2-no1-zdab 1665tolhs-tetradi-no1-bhsdab1716amthiaz-24oxman2-imo-bhsdab 1666mam2py-am3diaz-men-bhsdab17172py-pymea-aco-psdab 1667bimhs-pyma2-chexo-zorn1718imhs-mepipe-no2-glyzdap 16682py-ams2-ocho-csdap17194pmhs-n2nme2n-imo-glubzla 1669ppy-diphmem-5pho-glupha1720bimhs-dimephmem-napo-betadcph 16702py-dimephmem-ocho-asppha1721z-edia2-oem-nbetapy 1671dhim-pipmes-chexo-asppha1722thpym-edian2-mes-bhsdap 1672thpym-pentadi-men-tsdap1723tolhs-dimephmem-ocho-betapy 1673mam2py-thizn-men-bhsdap1724pyrhs-trias-men-asppha 1674impy-eta2s-chexo-thizzdap1725mam2py-n2o2n-napo-glyzdap 1675impy-eta-emo-zdabs1726thpym-thizo-meo-betainyl 1676bim-hexas-4amo-betaet1727chhs-ams2-mes-betainyl 1677pippy-m25thizman2-chexo-1728me2py-am3-sem-npsdap

bphabs17292py-dio-imo-bphabs 1678nmhs-thizn-chexo-psdab1730mam2py-indan2-oem-betainyl 1679impy-3pazin-5pho-psdap1731dhim-dimen-emo-betadcph 16802py-tridi-chexo-glubzla1732pippy-24thiman-men-zdap 16812py-dis-cnmo-betapy1733impy-dis-emo-aspibua 1682pippy-mepipen2-meo-psdap1734imhs-amn2-5pho-zdab 1683mam2py-dimen-emo-aspbzla1735impy-m25thiz-ocho-csdap 1684mam2py-dis-napo-zdap1736bz-pentadi-meo-bsdap 16852py-pazin-ocho-psdab1737thpym-mepipe-no1-zdab 1686me2py-amo2-napo-asppha17382py-eta-peo-aspibua 1687impy-m25thiz-emo-ppsdap1739mam2py-din-fo-tsdap 1688me2py-thizs-mmen-mezphe1740thpym-edian2-5pho-psdab 1689bim-eta-ocho-bsdap1741thpym-tetradi-oem-ibsdap 1690moegua-mepipen2-oem-glyzdap1742amim-amn3-imo-bsdap 1691dmthpym-m25thiz-eoco-betadcph1743hythpym-eta-fo-aspibua 1692prhs-trias-meteto-zdabs1744ppy-24oxman2-imo-zdab 1693thpym-m24thizman2-fo-mezphe1745edothpym-dimephmem-5amo-osdap 1694impy-edian2-no2-psdap1746pyrhs-dimephmem-meo-betapy 1695phhs-eta-napo-dfzdap1747bhs-mepipe-ocho-bhsdap 1696impy-hexadi-oem-zlys17482py-mepipe-no1-bsdap 1697pyraz-dich-5amo-psdap1749piraz-dimephmep-emo-aspibua 1698npip-pnymea-mes-zdap1750bhs-eta-meo-zdap 1699chmhs-2pazin-men-aspbzla1751piraz-dimephmep-emo-dfzdap 1700edothpym-dis-nmo-mezphe1752me2py-dimephmem-imo-bhsdap 1701dhim-diphmem-no1-ibsdap1753npip-amo2-no2-betapy 1754bhs-dimephmep-4pho-osdap1805dhim-3pazin-cnmo-bhsdap 17552py-edian2-oem-zdap1806z-pipmea-eoco-bphabs 1756dhim-pipmea-emo-zdab1807mam2py-am3diaz-5amo-bsdap 1757nim-24thiz-pro-aspibua1808imhs-24thiz-imo-asppha 1758dhim-edian2-daco-glyzdap1809morhs-m24thizman2-chexo- 17594pmhs-trias-no1-betadcphbhsdab 1760edothpym-dis-no1-bphabs1810phpip-diphmep-oem-dfzdap 1761impy-m24thizman2-cpeo-bhsdab1811me2py-ams2-napo-mezphe 1762bim-eta-mes-zdab1812phpip-24thiz-no1-psdap 1763nmor-eta2s-emo-psdap1813bhs-edian2-no2-bsdap 1764dhim-tridi-mes-zdap1814dhim-edian2-cnmo-dfzdap 1765impy-mepipe2-oem-nbetameph1815bimhs-pipmea-meto-ibsdap 1766bim-m24thiman2-5amo-bsdap1816piraz-dimephmep-meo-glyzdap 1767impy-amn3-imo-bhsdap1817mepip-mepipen2-napo-psdab 1768amim-25thizman2-emo-aspibua1818imhs-edian2-oem-psdap 1769ibhs-n2nme2n-imo-aspbzla1819mam2py-dimephmem-pheo-mezphe 17704pmhs-mepipe2-oem-nbetab1820thpym-mepipen2-cno-zdabs

naphth1821bim-mepipen2-no2-bnsdap 1771thpym-24thizman2-fo-zdabs1822hythpym-ams2-5pho-psdab 1772chmhs-dimephmem-napo-dfzdap1823hythpym-pyma2-daco-mezphe 1773me2py-pyma2-daco-ibsdap1824impy-dis-oeto-aspbzla 1774bim-mepazin-cnmo-zorn1825chmhs-tridi-imo-psdap 1775me2py-tetradi-ocho-zdapee1826imhs-m24thizman2-oem-bhsdap 1776amim-pyma2-no1-csdap1827npip-dimephmem-men-bphabs 1777am2py-mepazin-oem-bhsdap1828pippy-trias-imo-bhsdab 1778bhs-amn2-5pho-bhsdap1829tolhs-pymea-no1-dfzdap 1779edothpym-pazin-napo-csdap1830amim-m24thizman2-imo-thizzdap 1780thpym-amo3-no2-csdap1831me2py-eta-emo-psdab 1781am4py-dimephmem-mes-dfzdap1832bim-pazin-5pho-betapy 1782amim-edia2-sem-nbetabnaphth1833amim-thizn-fo-zdapee 17832py-propn-chexo-betapy1834am2py-mepipe-pyo-bhsdap 1784bimhs-din-mecpo-psdap1835mam2py-thizn-5pho-dfzdap 1785bimhs-mepipe-imo-bhsdap1836dhim-24thizman2-napo-psdab 1786mepip-eta-nmo-asppha1837me2py-25oxman2-napo-dfzdap 1787tolhs-2pazin-napo-bhsdap1838amim-am2-oem-nbetapy 1788me2py-dipch-chexo-zdabs1839bim-24thiz-cno-glyzdap 17892py-amn2-no2-zdap1840piraz-2pazin-chexo-betaet 1790bim-mepazin-oem-betainyl1841cl3pyme-mepazin-chexo-glyzdap 1791thpym-eta-meo-betapy18422py-ams2-eoco-betapy 1792impy-dimephmep-5amo-bnsdap1843mam2py-am2-oem-nzdap 1793piraz-2pazin-no2-aspibua1844imhs-pazin-5pho-betapy 1794imhs-pnymea-cnmo-zdap1845thpym-edian2-eoco-zdab 1795thpym-m25thiman2-fo-zdap1846impy-m24thizman2-ocho-betapy 1796amim-dimen-no2-aspibua1847cl3pyme-diphmem-5pho-bnsdap 1797thpym-amn2-eoco-psdab18484pmhs-ams2-pheo-oxal 1798amim-tetradi-ocho-aspbzla18492py-pymea-no1-betadcph 1799pippy-dis-fo-betadcph1850pippy-am3-oem-nbetapy 1800bhs-m24oxman2-meto-glubzla1851piraz-tridi-pro-betainyl 1801im-m24oxman2-eoco-psdap18522py-eta-men-bnsdap 1802hythpym-amo2-emo-glubzla1853phpip-mepipe-eoco-betainyl 1803am2py-pipa-mommo-ibsdap1854edothpym-amn3-pyo-zdabs 1804bhs-amn2-ocho-bhsdap1855im-pentas-ocho-betadcph 1856cl3pyme-ams2-mes-betadcph1906imhs-am2-sem-nbetameph 1857bim-pyma2-ocho-betadcph1907dmthpym-pymea-imo-aspibua 1858bim-amn2-no1-bsdap1908bhs-mea-imo-betapy 1859imhs-pazin-no1-bsdap1909hythpym-mepipe2-sem-nzdap 1860dhim-dimephmep-oeto-betainyl1910menim-24thiman2-napo-bhsdab 1861bim-thizn-no2-zdab1911amim-pazin-fo-zdap 1862prhs-pazin-5pho-csdap1912amim-props-no1-zdab 1863chmhs-m24oxman2-mommo-bphabs1913bim-eta-5pho-psdab 18642py-mepipen2-men-dfzdap1914am2py-thizs-eoco-zdap 1865npip-edia2-sem-nbetameph1915phpip-dimen-5pho-betainyl 1866bhs-tridi-ocho-bnsdap1916bhs-edian2-eoco-bnsdap 1867bhs-pazin-no2-betadcph1917am2py-dimephmem-emo-bsdap 1868moegua-amo2-chexo-zdap1918bz-mepipe-meo-glubzla 1869mepip-amn3-emo-aspibua1919me2py-m25thiz-no2-aspbzla 1870dmthpym-am3-sem-nbeta34-1920ppy-pyma2-men-csdap

dimeoph1921me2py-ams2-mes-bphabs 1871emnim-diphmem-oeto-zlys1922bhs-dimen-emo-bphabs 1872ibhs-m25thiz-chexo-bphabs1923emnim-24oxman2-fo-betapy 1873thpym-pyma2-imo-glyzdap1924imhs-diphmem-emo-aspibua 1874gua-24thiz-oeto-psdap1925hythpym-mepipe-cnmo-betadcph 1875am2py-thizn-mes-csdap1926dhim-n24thiman-cno-csdap 1876amthiaz-24thizman2-pheo-csdap1927mam2py-pipmea-nmo-csdap 1877am4py-mepipe2-oem-nbetameph1928z-ms-meo-zdab 1878ec-m25thiman2-meo-aspibua1929am4py-pyma2-cno-psdap 1879dhim-amn3-cpro-bhsdab1930am4py-mepazin-no2-betainyl 1880dmthpym-m24thizman2-5amo-1931thpym-eta-meo-psdab

bhsdap1932chhs-pymea-napo-bhsdap 1881imhs-mepipe-oem-zdap1933pyraz-m24thizman2-meo-tsdap 1882bim-pazin-oem-betapy1934pippy-24thizman2-4amo-mezphe 1883bhs-eta-oem-betapy1935imhs-edian2-eoco-zdap 1884dhim-props-imo-zlys1936amim-thizo-5amo-bnsdap 1885thpym-pipa-eoco-mezphe1937me2py-24thizman2-cnmo-zdabs 18862py-ams2-5pho-zdabs1938thpym-pazin-ocho-betapy 1887hythpym-amo2-eoco-mezphe1939impy-m24thizman2-5amo-aspbzla 1888bim-eta-meo-zdap1940amim-tridi-5amo-asppha 1889dhim-pipmes-5pho-zdap1941thpym-dimephmep-emo-glyzdap 1890hythpym-thizn-mes-zdabs1942thpym-am3diaz-napo-csdap 1891gua-pipa-fo-bphabs1943prhs-pentas-eoco-bsdap 1892nmhs-pipmea-mes-zdabs1944phhs-pipmea-5amo-dfzdap 1893dhim-trias-imo-zdab1945prhs-dich-mes-zdapee 1894mam2py-pymea-eoco-csdap1946thpym-edian2-5pho-bnsdap 1895imhs-eta-eoco-betapy1947piraz-m24thizman2-napo-bhsdap 1896dpam-mepazin-4amo-glyzdap1948dmam-amn3-cnmo-zdabs 1897bimhs-diphmep-no2-thizzdap1949phpip-pymea-cno-aspibua 1898am2py-m24thizman2-mes-psdap1950bhs-pipa-mes-ppsdap 1899nmhs-am2-oem-nbetapy1951am4py-trias-mes-bphabs 1900bhs-mepipen2-napo-bhsdap1952am2py-dimephmem-chexo-psdab 1901dhim-diphmem-mes-zlys1953dmthpym-dimephmem-mmen- 1902me2py-25thiz-eoco-zdabsbetadcph 19032py-dis-imo-psdap1954pippy-mepipen2-emo-betadcph 1904bim-mepipe-5pho-bnsdap1955bim-mepipe-meo-betapy 1905edothpym-pazin-mes-betainyl1956moegua-mepipe-5amo-zdabs 1957dhim-mepipen2-emo-bphabs2008dmam-amo3-ocho-bhsdap 1958z-eta-no2-betadcph2009impy-am3-sem-nzdab 1959dpam-pnymea-men-bhsdab2010dpam-2pazin-daco-asppha 1960bimhs-diphmem-chexo-bphabs2011bhs-m25thiz-chexo-psdap 19612pmhs-thizn-mes-mezphe2012impy-diaz-peo-aspibua 1962piraz-25oxman2-5pho-zdap2013dhim-pymea-meo-aspibua 1963imhs-amn2-5pho-bsdap2014bhs-pipmea-no1-betainyl 1964phhs-24oxman2-eoco-zdapee2015bimhs-n24thiman-mes-betapy 19652py-pazin-ocho-aspibua2016dhim-pipmes-fo-psdap 1966ibhs-dipch-emo-betapy2017phhs-dimen-ocho-zdab 1967bhs-amn2-eoco-psdap2018thpym-dipch-no2-bphabs 1968thpym-tridi-4amo-asppha2019bhs-mea-meteto-asppha 1969ec-ams2-meo-aspibua2020morhs-tetradi-4pho-psdab 19702py-pazin-meo-psdap2021amthiaz-n2nme2n-baeo-bnsdap 19712py-pazin-fo-csdap2022pippy-mepipe-eoco-bhsdab 1972thpym-pazin-ocho-bsdap20232py-amn2-no1-bnsdap 1973moegua-diphmep-meo-betadcph2024me2py-25oxman2-imo-psdab 1974am4py-diphmep-5pho-asppha2025bhs-edian2-no2-bnsdap 19752py-edian2-no1-psdab2026bhs-mepipe-emo-glyzdap 1976menim-mepipe-ocho-zdab2027cl3pyme-m25thiz-fo-asppha 1977chmhs-2pazin-fo-betainyl2028impy-amo2-napo-ibsdap 1978amthiaz-25thizman2-eoco-2029ppy-dimephmep-5amo-csdap

betapy2030chhs-dimen-mes-betapy 1979imhs-amo2-mes-mezphe2031hythpym-ams2-ocho-bhsdap 1980amim-ams2-fo-oxal2032bim-thizn-emo-psdap 1981dhim-pymea-men-bphabs20332py-eta-ocho-bsdap 19822pmhs-din-no2-bhsdap2034bz-am3-oem-nbetapy 1983am4py-25thiman2-no1-betadcph2035ibhs-mepipen2-pro-zdabs 1984edothpym-ams2-baeo-bnsdap2036pippy-dimephmep-no1-mezphe 1985nim-dis-eoco-aspibua2037piraz-m25thiz-oem-zdap 1986mepip-edia2-sem-npsdap2038cl3pyme-dimephmem-men-aspibua 1987hythpym-pymea-mecpo-glubzla20392py-25thiman2-5pho-betainyl 1988ppy-am3-oem-npsdap20402py-tridi-napo-dfzdap 1989hythpym-edian2-4pho-glyzdap2041dhim-dimephmem-pro-bhsdap 1990amim-24thiman-ocho-betadcph2042dmthpym-am3-sem-nzdab 1991imhs-eta-oem-bnsdap2043morhs-m25thiz-meo-zdab 1992am2py-mepipe-napo-zorn2044pippy-dimen-pyo-mezphe 1993morhs-mepazin-oeto-ibsdap2045amim-tetradi-no2-aspibua 1994bim-dimephmem-ocho-betainyl2046piraz-m25oxman2-ocho-psdap 1995am2py-pipmea-oem-zdap2047me2py-mepipe-mes-bhsdab 1996dhim-pyma2-no2-bhsdab2048pippy-diphmem-men-betadcph 1997moegua-ams2-ocho-zdab2049phhs-pazi2n-chexo-glyzdap 1998bim-eta-ocho-psdab2050piraz-trias-oem-bphabs 1999impy-edian2-eoco-glubzla20512py-am3-oem-nzdab 2000bimhs-n24thiman-emo-betadcph2052n2py-pipa-fo-csdap 2001pyr-eta-5amo-bnsdap2053mam2py-24thiz-paco-bhsdab 2002pyrhs-thizn-baeo-psdab2054phhs-amn2-mes-betadcph 20032py-ms-meo-psdap2055mam2py-pazin-napo-bphabs 2004chmhs-ams3-mes-bphabs2056bhs-pnymea-mommo-aval 2005cl3pyme-3pazin-emo-psdap2057bim-pazin-eoco-bnsdap 2006imhs-amo2-chexo-aspbzla2058bimhs-amn3-eoco-glyzdap 2007piraz-pentadi-4amo-ppsdap2059me2py-eta2s-5amo-dfzdap 2060hythpym-eta-ocho-bhsdab2110dhim-amo2-peo-psdab 2061menim-mepipe-men-zdabs21112pmhs-tetradi-no1-ppsdap 2062am2py-pipmea-oem-bnsdap21122py-dich-5amo-betadcph 2063tolhs-diphmep-fo-glyzdap2113hythpym-24thiz-ocho-bsdap 2064bim-24thizman2-men-aspibua2114menim-mepipen2-oem-csdap 2065am-pazin-no1-zdabs21154pmhs-pipa-no1-glyzdap 2066moegua-2pazin-meteto-zdabs2116dhim-butn-cpro-zdap 2067impy-24thiz-eoco-betapy2117hythpym-am3-sem-nbetameph 2068me-edian2-imo-asppha2118bhs-edia2-sem-nzdap 2069mam2py-dimen-imo-glyzdap2119edothpym-dis-no2-bphabs 2070mam2py-thizn-imo-betadcph2120bimhs-din-meteto-mezphe 2071thpym-dimen-4pho-aspibua2121thpym-ams2-ocho-betadcph 2072bim-ams2-5amo-bsdap2122menim-mepazin-eoco-psdab 2073bhs-25oxman2-fo-aspbzla2123dhim-tridi-oem-bsdap 2074morhs-props-oem-psdab2124pippy-amn2-5amo-asppha 2075phpip-amn2-5amo-bsdap2125amim-dis-eoco-bsdap 2076edothpym-2pazin-pro-asppha2126thpym-edia2-sem-nbetameph 2077imhs-pnymea-men-betainyl2127bim-eta-no1-zdab 2078amim-props-pyo-psdapee2128dhim-24thizman2-4amo-asppha 20792py-mepipe2-sem-nbeta34-21292py-pazin-eoco-bnsdap

dimeoph2130bim-amn3-paco-bphabs 2080piraz-dio-imo-betainyl2131imhs-dimen-no2-psdab 2081bz-amn2-napo-csdap2132cl3pyme-25thiz-eoco-zlys 2082thpym-dimen-no2-bnsdap2133npip-diphmep-chexo-csdap 2083amim-butn-ocho-zdabs2134dhim-mepipen2-aco-zdab 2084prhs-pipa-nmo-ibsdap2135bhs-mepipe-ocho-betapy 2085ec-tridi-napo-bphabs2136mam2py-pnymea-oem-mezphe 2086piraz-pipa-oeto-zdabs2137dpam-am2-oem-nbetabnaphth 2087menim-thizn-no1-zdab2138edothpym-trias-chexo-betainyl 2088thpym-amn2-no1-zdap2139imhs-n24thiman-no2-aspaba 2089me2py-24thiman2-daco-bsdap2140nim-pipmes-baeo-mezphe 2090thpym-mepipe-mes-betapy2141bhs-amn2-eoco-bnsdap 2091am2py-pyma2-no2-osdap2142me-dis-5pho-zdab 20922py-pazin-mes-dfzdap2143bimhs-m25thiz-emo-psdab 2093dmam-diphmem-chexo-zdabs2144impy-dimephmem-oeto-csdap 2094pyr-pipa-men-bhsdap2145me2py-din-5pho-zdabs 2095imhs-m25thiz-fo-bnsdap2146impy-24thiz-imo-mezphe 2096im-dis-5pho-dfzdap2147am-amo3-no1-glyzdap 2097piraz-24thiman2-imo-betainyl2148dhim-am3-sem-npsdap 2098hythpym-diphmem-paco-betainyl2149dhim-dis-5amo-psdap 2099phhs-25oxman2-5pho-glupha21502py-mepazin-peo-bhsdap 2100bim-eta-mes-bsdap2151thpym-dis-5amo-aspbzla 2101impy-am3-sem-nbetapy2152pippy-dimephmem-5pho-glyzdap 2102bim-24thizman2-no2-aspaba2153mepip-mepipe-chexo-psdap 2103me2py-thizn-5pho-glyzdap2154dhim-amn2-meto-betainyl 2104amim-dimephmep-5pho-glubzla2155bhs-dimephmem-mes-aspbzla 2105bimhs-m25thiz-eoco-betainyl2156impy-m25thiz-daco-bsdap 2106piraz-24thizman2-meteto-2157bim-thizo-oem-bnsdap

betapy2158amim-mepipe-nol-betadcph 2107bhs-edian2-meteto-bsdap2159bim-25oxman2-napo-bhsdap 2108chmhs-3pazin-no2-zdabs2160piraz-dipch-napo-zdap 2109bhs-amn3-emo-dfzdap2161bhs-tridi-paco-betapy 2162mam2py-m25thiman2-chexo-2213piraz-pyma2-men-csdap

betainyl2214imhs-dis-oeto-psdapee 2163chmhs-am3-sem-nbetameph2215menim-trias-men-betainyl 2164me2py-pipmeo-no1-zdap2216ibhs-diphmem-no2-psdap 2165pippy-m24thiz-daco-betainyl2217z-24thiman-no2-betainyl 2166piraz-dimephmep-paco-dfzdap2218bhs-eta-emo-asppha 2167mam2py-25oxman2-5pho-aspibua2219bhs-propn-cpro-dfzdap 2168bhs-eta-5pho-bhsdap2220bimhs-dimen-chexo-zdabs 2169bim-thizn-eoco-aspbzla2221bim-din-mes-tsdap 2170me2py-n2o2n-5amo-bnsdap2222dhim-25thiz-napo-bnsdap 2171bim-edia2-sem-nbetapy2223dpam-m24thizman2-chexo-bhsdab 2172am2py-din-no1-mezphe2224bimhs-ms-oeto-aspbzla 21732py-tetras-eoco-bphabs22252py-n2o2n-5pho-aspbzla 2174bimhs-am3diaz-fo-dfzdap22264pmhs-mepipen2-mommo-zdapee 2175dpam-24thizman2-5pho-zdabs2227am2py-dimephmep-oem-psdap 2176bimhs-mepipen2-ocho-betapy2228bimhs-24thizman2-imo-mezphe 2177bim-edian2-no2-bhsdap2229am2py-edia2-sem-nbetameph 2178edothpym-dimephmep-5amo-bsdap2230amim-ams2-cpro-aspbzla 2179bzl-ams2-oeto-csdap2231chhs-24thiz-5amo-tsdap 2180tolhs-n2nme2n-chexo-glubzla2232ppy-dis-oem-glyzdap 2181impy-pymea-5amo-betadcph2233am-dimephmem-napo-tsdap 21822py-m24thizman2-fo-bhsdap2234am2py-diphmem-chexo-psdap 2183amim-pipa-meteto-bsdap2235thpym-mepipe-ocho-betapy 2184bhs-25oxman2-no2-aspbzla2236npip-butn-ocho-bsdap 2185thpym-pentadi-oeto-bsdap2237me2py-diphmem-cno-tsdap 2186me2py-diphmep-daco-psdap2238thpym-mepipe-no2-glyzdap 2187bim-edian2-hso-bnsdap2239tolhs-mepipen2-imo-psdapee 2188dhim-dimephmem-hso-asppha2240amim-diphmep-peo-bsdap 2189pippy-thizn-eoco-oxal2241piraz-amn2-5amo-bphabs 2190impy-ms-mes-betapy2242dhim-hexadi-ocho-csdap 2191piraz-edia2-sem-npsdap2243hythpym-3diaz-4pho-bhsdab 2192am2py-m25thiz-eoco-aspibua2244me2py-diphmem-oem-aval 2193chhs-24thiz-meo-bhsdap2245am-mepipen2-eoco-mezphe 2194phhs-mepipen2-peo-oxal2246am2py-m25thiz-oem-glyzdap 2195pyrhs-eta-peo-oxal2247imhs-pipa-emo-bsdap 2196piraz-pipa-imo-bnsdap2248piraz-trias-aco-bhsdap 2197morhs-din-men-asppha2249bim-trias-chexo-psdab 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2268menim-dimen-5amo-psdap2320bim-diphmem-eoco-betainyl 2269pippy-diphmem-eoco-bhsdap2321impy-25oxman2-pyo-betadcph 2270morhs-propn-eoco-aspaba2322bim-25oxman2-5pho-psdap 22712py-pazin-ocho-zdap2323bim-diphmep-mes-ppsdap 2272fthpym-thizn-4amo-bsdap2324bhs-pazin-eoco-psdab 2273menim-tridi-baeo-bnsdap2325me2py-mepipe-nmo-dfzdap 2274hythpym-pymea-oeto-bsdap2326prhs-pipa-mecpo-zdab 2275piraz-pipa-oem-psdap2327dhim-m25oxman2-ocho-bsdap 2276deam-dimephmem-napo-psdab2328hythpym-24thizman2-pro-bnsdap 2277dhim-tetras-cnmo-bnsdap2329bhs-24thiz-cpeo-bsdap 2278amim-diaz-chexo-bsdap2330imhs-mepipe2-sem-nbetameph 2279imhs-mepipe-ocho-bsdap2331z-25thizman2-ocho-aspibua 2280ibhs-24thiz-chexo-psdab2332imhs-trias-5amo-bsdap 2281chmhs-din-eoco-bhsdab2333thpym-ams2-ocho-glyzdap 2282imhs-eta-oem-zdab2334imhs-pazin-eoco-zdap 2283bhs-n2nme2n-no2-tsdap2335ibhs-24thizman2-oem-bsdap 2284amim-pipa-meo-oxal2336bhs-hexadi-men-bphabs 22852py-m24thiz-mommo-bhsdab2337thpym-pipmea-5amo-aspibua 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bhsdap10066bimhs-mepipe-napo-osdap 10015npip-m25thizman2-no1-aspibua10067mam2py-diphmem-emo-glyzdap 10016imhs-25oxman2-5pho-bnsdap10068amim-pyma2-ocho-csdap 10017bhs-eta-men-zorn10069thpym-ams2-imo-mezphe 10070thpym-diphmep-nmo-oxal10121thpym-mepipe-no1-zdap 10071hythpym-hexadi-daco-bsdap101222pmhs-mepipe2-sem-nzdab 10072piraz-m24thizman2-5pho-zorn10123impy-amn2-meteto-betaet 10073thpym-dimephmem-no1-csdap10124thpym-pyma2-meteto-betainyl 10074mam2py-amo3-eoco-mezphe10125am4py-24thizman2-men-bnsdap 10075impy-eta-5pho-zdab10126nim-25thiman2-ocho-aspbzla 10076pippy-diphmep-fo-zdabs10127n2py-mepipe-mes-aspibua 10077piraz-dipch-cnmo-bphabs10128pippy-m25oxman2-5pho-zdabs 10078dhim-pazin-pro-bsdap10129dpam-edia2-sem-nzdap 100792py-mepipe-5pho-psdab10130bimhs-din-napo-asppha 10080edothpym-mepipe-napo-dfzdap10131me2py-mepipe-5pho-bphabs 10081chmhs-amn2-cpeo-dfzdap10132amthiaz-trias-hso-betainyl 10082bhs-hexadi-daco-zdabs10133me2py-25thiman2-chexo-dfzdap 10083amim-25thizman2-ocho-zdap10134pippy-dimen-hso-betapy 100842py-amn2-napo-betadcph10135piraz-amn2-5pho-csdap 10085emnim-mepipe2-sem-npsdap10136me2py-amo2-napo-bnsdap 10086npip-24thiman2-cno-glyzdap10137pippy-am2-sem-nzdap 10087imhs-dimephmep-emo-asppha10138imhs-n24thiman-fo-psdap 10088impy-amn2-paco-zdabs10139n2py-pipmeo-no1-betadcph 10089deam-pyma2-5amo-bhsdap10140dmam-24thizman2-nmo-betaet 10090piraz-tridi-chexo-aspaba101412py-thizn-5pho-dfzdap 10091me2py-m25oxman2-meo-mezphe10142pippy-hexadi-fo-bhsdab 10092am2py-edian2-imo-bhsdab10143amthiaz-ams2-oem-asppha 10093dmam-pnymea-no2-asppha10144emnim-amo2-cpeo-aspibua 10094imhs-edian2-fo-bsdap101452py-pazin-no1-zdab 10095am2py-amo2-no1-zdab10146thpym-pazin-oem-bsdap 10096mepip-mepazin-napo-csdap10147thpym-eta-meo-bnsdap 10097me-edian2-aco-psdap10148pippy-dimephmep-mes-bhsdab 100982py-edian2-no1-bhsdap10149piraz-amo3-no2-zdabs 10099amim-pazin-oeto-glubzla10150amim-amn3-fo-zdabs 10100pyraz-am2-sem-nbetabnaphth10151mam2py-diphmem-chexo-bhsdab 10101mam2py-pnymea-men-aspbzla10152thpym-amn2-mes-betapy 10102dhim-pyma2-no2-aspaba10153bim-tetradi-eoco-zdab 10103bim-diphmem-chexo-psdab101542py-dimephmem-meo-psdap 10104impy-dipch-imo-psdab10155hythpym-dimephmem-imo-bsdap 10105hythpym-pyma2-men-bhsdab10156menim-thizo-ocho-asppha 10106pippy-mepipen2-men-betainyl10157dmam-ams3-4pho-bsdap 10107bhs-amn2-mes-psdab10158thpym-mepipe-oem-bsdap 10108nmor-thizs-fo-zdap10159dhim-m24thizman2-5amo-betaet 10109tolhs-dimen-chexo-dfzdap10160dmthpym-m25thiz-men-bhsdab 10110dmam-amn3-napo-bhsdap10161bhs-amn2-oem-bhsdap 101112pmhs-amn2-imo-zdap101622py-pazin-no2-bsdap 10112dmbim-pyma2-5pho-aspibua10163hythpym-pipmes-meo-betapy 10113impy-tetradi-mes-glyzdap10164prhs-m24oxman2-no2-ppsdap 10114bimhs-pentadi-meo-zdab10165piraz-diphmem-no2-betainyl 10115imhs-eta-no1-psdab10166bhs-24thiz-men-glupha 10116dhim-dimephmep-nmo-psdab10167bim-eta2s-men-psdap 10117fthpym-24thizman2-101682pmhs-diphmep-meto-zdab

5pho-thizzdap10169amim-mepipe-emo-betadcph 10118bim-dimephmep-eoco-ppsdap10170piraz-mepazin-emo-psdap 10119bhs-mepipe-5pho-bsdap10171bim-pazin-meo-zdap 10120imhs-pazin-meo-bnsdap101722py-24thiz-cpro-zdap 101732py-diaz-men-bphabs10224mam2py-diphmem-imo-glubzla 10174bim-eta-mes-bnsdap10225bhs-pazin-no1-bnsdap 10175pippy-pyma2-imo-psdap10226phpip-3pazin-oem-bsdap 10176bhs-3diaz-imo-glyzdap10227dhim-m25thiz-chexo-zdab 10177pippy-thizn-men-glyzdap10228pippy-eta-meo-zdab 10178bhs-dimen-5pho-glubzla102292py-pazin-5amo-aspbzla 10179bhs-amn3-5pho-betadcph10230dhim-24thizman2-oeto-bphabs 10180dhim-25oxman2-no2-bhsdab10231nmhs-thizs-meto-mezphe 101812py-pazin-oem-bsdap10232amim-pentas-nmo-oxal 10182imhs-am2-oem-nbetapy10233amim-mepipe2-sem-nzdab 10183bim-mepipen2-fo-bphabs10234bhs-pyma2-4amo-ppsdap 10184dpam-24thiz-imo-psdab10235npip-dimephmep-pheo-betainyl 10185impy-edian2-4pho-bhsdap10236pippy-diphmem-oem-bsdap 101864pmhs-dimephmem-chexo-bhsdap10237pippy-eta-peo-csdap 10187dmthpym-dimephmem-cno-zdab10238dhim-tetradi-mes-bnsdap 10188bhs-eta-meo-betapy10239piraz-dimephmem-ocho-bhsdab 101892py-dis-fo-glubzla102402pmhs-m24thizman2-4amo-psdab 10190edothpym-pnymea-mecpo-10241impy-dimephmep-ocho-dfzdap

glyzdap10242hythpym-mepipe-men-psdab 10191phpip-pymea-eoco-zdab10243pippy-pymea-chexo-aspbzla 10192phpip-edian2-fo-bhsdab10244fthpym-m24thizman2-nmo- 10193ppy-mepipe2-sem-nbetabnaphthbetapy 10194hythpym-n2o2n-emo-bhsdab10245bhs-amn2-no1-psdab 10195amthiaz-pazin-eoco-zdab10246bim-dis-pheo-zdab 10196impy-diphmem-pyo-zdapee10247piraz-tetradi-mecpo-aspibua 10197bhs-m25thizman2-pyo-asppha10248moegua-mepazin-mmen-aspbzla 10198n2py-pazin-imo-mezphe10249gua-diphmem-5amo-mezphe 10199dhim-m24thizman2-oem-bhsdap10250bim-24thizman2-ocho-psdab 102002py-tetradi-meo-bhsdab10251emnim-diphmem-fo-psdap 10201bhs-mepipe-ocho-asppha10252bim-m25thiz-aco-zdab 10202dmbim-mepazin-emo-aval102532py-mepipe-oem-psdap 10203piraz-amo2-fo-aspibua10254thpym-24thizman2-meo-psdap 10204imhs-pazin-mes-bhsdap10255dmthpym-amo2-men-bhsdap 10205am2py-dimen-no2-bphabs10256gua-dimephmep-mes-betapy 10206thpym-ams2-napo-psdab10257dmbim-dimephmep-oeto-psdap 10207emnim-amo3-5pho-csdap10258pippy-pazin-nmo-aspibua 10208mam2py-am2-oem-nbetapy10259gua-dio-cnmo-zlys 10209bim-dimephmep-ocho-psdap10260amthiaz-amn3-cno-mezphe 10210bim-pipa-pyo-zdab10261bz-pazin-mmen-zdab 10211bhs-edian2-oem-betapy10262piraz-dis-mes-zdap 10212bz-propn-no1-psdap10263bimhs-pazi2n-pheo-aspibua 10213dmbim-hexas-oeto-aspibua10264imhs-pazin-meo-betapy 10214dpam-dis-nmo-csdap10265dhim-amo2-5pho-zdapee 10215tolhs-dimephmem-emo-dfzdap10266bim-mepipe-cpro-tsdap 102162py-edian2-no1-bsdap10267bhs-diphmep-eoco-glyzdap 10217imhs-thizs-chexo-bphabs102682py-m24thiz-men-bhsdab 10218ibhs-edia2-sem-nbetameph10269fthpym-m24thizman2-chexo- 10219nim-pipmea-eoco-dfzdapcsdap 10220ppy-24thiz-chexo-aspibua10270cl3pyme-dimephmep-4amo- 10221amim-24thiz-chexo-bhsdapbetadcph 10222bimhs-thizn-imo-aspibua10271nim-24thizman2-meto-aspbzla 10223menim-24thizman2-meo-bhsdab102722py-edian2-eoco-zdap 10273dhim-24thiz-emo-glyzdap10324thpym-edian2-no2-psdab 10274piraz-pipmeo-mommo-zlys10325impy-pipmes-pro-betainyl 10275ibhs-eta-men-aspbzla10326moegua-ams2-5amo-bhsdap 10276bimhs-diaz-no2-zdabs10327amim-amn2-men-asppha 10277thpym-eta2s-4pho-aspbzla10328ibhs-pymea-no1-bhsdab 10278deam-diphmem-mes-bnsdap10329imhs-pyma2-men-bhsdab 10279emnim-diphmem-cpro-psdab10330amim-24thiz-mes-bhsdap 10280bimhs-25oxman2-cpro-zdap10331hythpym-amn2-no2-betadcph 10281bzl-24thiz-chexo-betapy10332me-tridi-men-asppha 10282pyr-diphmep-cnmo-aspibua10333bzl-thizn-5pho-dfzdap 10283piraz-mepazin-no2-aspbzla10334dhim-mepazin-emo-bnsdap 10284pippy-trias-mmen-csdap10335bhs-eta-ocho-psdap 10285pippy-edian2-5amo-psdap10336im-amo2-eoco-csdap 10286piraz-m25thiz-5pho-psdab10337dmthpym-m24thizman2- 10287dmbim-pipmea-ocho-dfzdap5pho-zdap 10288amthiaz-am2-sem-nbetapy10338thpym-24thizman2-no2-psdab 10289dmbim-hexadi-ocho-betadcph10339thpym-n24thiman-aco-psdab 10290n2py-dipch-mes-aspibua103402py-indan2-5pho-bnsdap 10291imhs-diphmep-cnmo-aspbzla10341piraz-pipmes-chexo-betainyl 10292pippy-indan2-chexo-psdab10342bimhs-eta-meo-bsdap 10293hythpym-thizn-pro-betadcph10343bhs-trias-emo-bphabs 10294impy-mea2s-men-bnsdap10344bim-pazin-meo-betapy 10295impy-diphmem-4pho-bhsdab10345pippy-pazin-mes-betadcph 10296impy-m25oxman2-ocho-psdap10346mam2py-dis-fo-bhsdap 10297chhs-pipa-emo-aspbzla10347piraz-thizs-emo-tsdap 10298cl3pyme-diphmep-cno-zdab10348fthpym-24thizman2-eoco-psdap 10299nmor-pnymea-5pho-asppha10349me-m25thizman2-pyo-psdab 10300impy-am3-sem-npsdap10350pippy-edian2-cno-csdap 10301cl3pyme-dimephmep-meteto-10351me2py-din-4amo-zdabs

aspaba10352mam2py-pentas-5pho-dfzdap 10302dhim-m24thizman2-ocho-zdabs10353bim-mepipe-eoco-zdab 10303amim-pyma2-napo-betadcph103542py-tridi-5pho-zdapee 10304pippy-eta-nmo-aspibua10355mam2py-ams2-no1-betapy 10305gua-am2-oem-npsdap10356moegua-n2nme2n-baeo-glyzdap 10306bimhs-24thiz-napo-dfzdap10357npip-pipmea-no1-psdab 10307prhs-24thizman2-oem-zorn10358amim-diphmep-imo-glyzdap 10308pippy-mepazin-4amo-glupha10359mam2py-dimephmep-emo-psdab 103092pmhs-din-fo-aspibua10360piraz-mepipe2-sem-nbetameph 103102py-amn2-no2-zdab10361bim-pyma2-cnmo-aspbzla 10311bhs-pnymea-chexo-bhsdap10362am2py-pipmea-4amo-aspbzla 10312pippy-24thiz-mes-zlys10363bhs-24thizman2-oem-csdap 10313dmthpym-pymea-napo-bhsdab10364bimhs-thizn-men-zdabs 103142py-din-5amo-zdab10365bim-pymea-5amo-betaet 10315bimhs-am3-sem-nbetameph10366amim-mea2s-mes-psdab 10316bim-mepazin-chexo-psdap10367edothpym-edian2-baeo- 10317bhs-thizs-oem-glyzdapbetadcph 10318bzl-pazin-mes-bsdap10368bim-m25thiman2-ocho-oxal 10319hythpym-dimen-5pho-thizzdap10369bim-mepipe-no1-zdap 10320amthiaz-pipa-nmo-bhsdap10370bz-amo2-no2-zdap 10321nmor-eta-imo-bsdap10371amim-thizs-ocho-asppha 10322am2py-thizo-oem-osdap103724pmhs-dis-no2-asppha 10323phpip-amn2-no2-dfzdap10373am2py-pentas-oem-bhsdab 10374hythpym-diphmep-mmen-mezphe104262py-mea2s-imo-aspbzla 103752py-trias-fo-betapy10427bim-pazin-no2-psdap 10376impy-diphmem-emo-osdap10428bim-eta-mes-psdab 10377dmbim-mepipen2-ocho-asppha10429am2py-thizn-emo-bhsdap 103782py-amn2-no2-psdab104302py-mepazin-5pho-psdap 10379imhs-amn2-5pho-asppha10431imhs-dimephmep-oem-zdab 10380me2py-dimephmem-ocho-glyzdap10432bhs-ams2-men-betapy 10381impy-hexas-fo-zdabs10433n2py-am2-oem-npsdap 10382thpym-pipa-emo-aspibua10434z-24thiz-5pho-csdap 10383imhs-diphmem-imo-psdab10435nmhs-dimen-daco-zlys 10384imhs-tridi-ocho-asppha10436menim-diphmep-mes-bphabs 10385mam2py-25oxman2-mes-psdap10437dhim-amn2-imo-dfzdap 10386nmhs-ams2-5pho-aspbzla10438am2py-pipa-mes-betapy 10387bz-m24thiman2-5pho-betadcph10439ppy-trias-no2-aspibua 10388bimhs-mepipen2-cpro-zdabs10440pyr-am3diaz-fo-bphabs 10389im-amo2-emo-zdab10441deam-dimen-mes-dfzdap 10390am2py-dis-eoco-asppha10442n2py-pyma2-no2-bhsdab 103912py-amn2-mes-zdab10443dhim-dimephmem-meo-aspibua 10392deam-dis-imo-mezphe10444bim-eta-eoco-bsdap 10393bim-edian2-meo-bsdap10445phpip-25oxman2-men-asppha 10394impy-tridi-5amo-bsdap10446pippy-eta-meteto-zdab 10395dhim-m24thiman2-oem-betapy10447imhs-m24thizman2-no2-bhsdab 10396im-tridi-emo-zdapee104482py-edia2-oem-nbetabnaphth 10397bhs-pazin-5pho-bsdap10449bhs-mepazin-fo-dfzdap 10398thpym-amn2-ocho-psdab10450bhs-tetradi-5pho-zdabs 10399phhs-m24thiz-napo-zdabs10451impy-m24thizman2-5amo-bphabs 10400pippy-hexadi-men-bnsdap10452nim-pnymea-5pho-aspbzla 10401am2py-tridi-chexo-bsdap10453bim-eta-no2-zdap 10402imhs-dimephmem-eoco-zdap10454dhim-mepipe-oeto-aspibua 10403bhs-edian2-oem-bsdap10455n2py-tridi-no2-zdap 10404hythpym-propa2s-cnmo-zdabs10456imhs-pymea-mes-bhsdap 10405amim-trias-chexo-asppha10457mam2py-dimen-chexo-betapy 10406ibhs-pnymea-napo-asppha10458prhs-pazin-oem-asppha 10407imhs-eta-no2-csdap10459bhs-pazin-no1-psdap 10408imhs-pipa-pheo-bhsdab10460amthiaz-ams2-men-bsdap 10409me2py-m25thiz-men-mezphe104612py-thizn-5amo-mezphe 10410menim-diphmep-5amo-psdap10462pippy-mepipe-men-bnsdap 10411chmhs-n2nme2n-meteto-aspbzla10463bhs-thizn-oem-psdap 10412impy-m24oxman2-napo-aval10464bhs-m24oxman2-men-betadcph 10413dhim-dis-eoco-glyzdap10465am2py-pipmea-mecpo-bhsdab 10414mam2py-pazin-5pho-bhsdap10466bimhs-propa2s-mes-zdapee 10415pyr-ams2-pyo-betaet10467bz-trias-men-psdab 10416bimhs-m25thiz-fo-dfzdap10468deam-24thizman2-napo-glupha 10417moegua-24thiz-ocho-asppha10469bhs-dimephmep-mes-aspbzla 10418chmhs-24thiman2-mes-bhsdab10470pippy-pazin-5pho-csdap 10419impy-diphmem-men-osdap10471prhs-dimen-no1-mezphe 10420impy-24thiz-emo-glyzdap10472dhim-mepipe-5pho-betainyl 10421imhs-mepipen2-ocho-dfzdap10473pippy-dis-ocho-zdab 10422am2py-amn3-5pho-asppha10474bimhs-pipa-mes-csdap 10423menim-amn3-napo-mezphe10475impy-tridi-ocho-bhsdap 10424bim-mepipe-eoco-bnsdap10476hythpym-thizo-cno-zdabs 10425amim-din-fo-aspibua10477dhim-3pazin-nmo-betapy 10478piraz-dimen-fo-glyzdap10528im-tetradi-mmen-dfzdap 10479nim-mepipe2-sem-npsdap10529fthpym-pyma2-ocho-bphabs 10480hythpym-24thizman2-cnmo-10530imhs-amn2-no1-zdab

zdapee10531bimhs-25oxman2-oem-dfzdap 10481dmam-amn2-fo-dfzdap10532me2py-mepipe2-oem-nzdap 10482piraz-thizn-eoco-betadcph10533am2py-thizn-no1-aspbzla 10483mam2py-hexas-eoco-zdabs10534ppy-eta2s-cpro-bhsdap 10484dhim-tridi-eoco-bhsdab10535me2py-24thizman2-oem-zdabs 10485hythpym-pnymea-emo-csdap10536impy-mepipe-meteto-psdab 10486mam2py-m25thiz-napo-betapy10537am2py-m24thiz-mes-bnsdap 10487moegua-edia2-sem-nbetapy10538pippy-dis-mes-mezphe 10488dhim-pymea-nmo-bphabs105392py-pazin-eoco-psdap 10489im-amn2-imo-glubzla10540thpym-eta-fo-zdap 10490gua-ams2-fo-dfzdap10541mam2py-mea2s-nmo-bnsdap 10491pippy-amn2-meo-betadcph105422py-pazin-emo-csdap 10492bhs-dio-cnmo-bhsdab10543im-pyma2-meto-dfzdap 104932py-eta-meo-bhsdap10544imhs-dimephmep-ocho-bhsdab 10494phhs-mea-fo-aval10545bim-mepipe-no2-bhsdab 104952py-dimen-oem-betapy10546bim-amn2-eoco-betapy 10496nmhs-mepazin-fo-psdap10547cl3pyme-dimen-no1-psdapee 10497edothpym-3pazin-no2-csdap10548ppy-dich-no2-csdap 10498me2py-tetras-no2-asppha10549bz-ms-imo-bhsdap 10499thpym-pyma2-hso-glyzdap10550ppy-dis-pyo-psdap 10500mam2py-eta-meto-psdab10551piraz-diaz-cno-glyzdap 10501ec-ams3-5amo-bhsdap10552pippy-trias-mmen-zdap 105022py-pazin-mes-psdab10553dpam-edia2-sem-nzdab 10503thpym-edian2-meo-bnsdap10554nmor-24thiman-meo-bnsdap 10504me-mepipen2-ocho-osdap10555bimhs-trias-mes-zdabs 10505bim-diaz-cno-zdabs10556npip-ams2-meo-glyzdap 10506amim-tetras-no1-dfzdap10557me2py-tetradi-mes-bnsdap 10507emnim-dimephmem-ocho-psdab10558cl3pyme-edian2-eoco-psdap 10508deam-dimen-cpro-psdapee10559bimhs-pnymea-chexo-tsdap 10509bhs-mepazin-mecpo-zorn10560nmhs-dimephmem-napo-mezphe 10510am2py-pentas-5pho-glupha10561bim-ams2-oem-psdap 10511ppy-din-fo-betaet10562bim-amn2-ocho-bnsdap 10512impy-mepipe-no1-glyzdap10563thpym-dis-mes-bphabs 10513pippy-m24thizman2-4amo-10564hythpym-ms-mmen-aval

aspbzla10565edothpym-diphmep-4pho-psdab 10514bimhs-dis-oem-aspbzla10566am2py-thizn-men-dfzdap 105152py-edian2-5pho-zdab10567dmthpym-pazi2n-imo-asppha 10516cl3pyme-tridi-meto-betainyl10568hythpym-dimen-men-ppsdap 10517piraz-25oxman2-eoco-betaet10569nmor-m24thizman2-ocho-bhsdab 10518me2py-am2-oem-nbetapy10570me-mea-aco-zdap 10519dhim-pymea-5pho-zlys10571dmbim-propa2s-no1-zdabs 10520thpym-trias-meteto-zdabs10572me2py-mepazin-fo-bphabs 10521thpym-mepipe-5pho-bhsdap10573thpym-eta2s-mes-aspibua 10522me2py-diphmep-4pho-psdap10574cl3pyme-amo2-chexo-betadcph 10523amim-butn-chexo-ibsdap10575amim-pyma2-eoco-zdabs 10524nmor-dimephmep-meo-osdap10576impy-dis-oeto-bsdap 105252py-edian2-ocho-zdab10577hythpym-amo2-ocho-ppsdap 105262py-diphmep-ocho-mezphe10578deam-pipa-eoco-zdapee 10527chmhs-ams2-napo-aspbzla10579z-amn2-5pho-psdap 10580bimhs-24thiz-no1-bphabs10630deam-tetradi-paco-psdab 105812py-dimen-no2-glubzla10631bim-pnymea-emo-betainyl 10582amim-m25thiz-5pho-betapy10632thpym-dimephmep-pro-thizzdap 10583piraz-dimephmem-hso-zdap10633imhs-pyma2-no1-aspibua 10584bhs-24thiz-baeo-zdap10634amthiaz-amo2-pheo-glyzdap 10585impy-24oxman2-emo-betainyl10635thpym-dimephmem-mecpo-csdap 10586dmthpym-pymea-meto-aspibua10636mam2py-pyma2-cnmo-bsdap 10587piraz-m24oxman2-imo-dfzdap10637am2py-24oxman2-5amo-bphabs 10588amthiaz-eta-5pho-glupha10638amim-tetras-5amo-mezphe 10589ibhs-pazi2n-fo-aspbzla10639mam2py-pymea-imo-betadcph 10590imhs-diphmem-chexo-zdab10640pyrhs-24thiz-5pho-psdap 10591pyraz-hexadi-oem-betaet10641ppy-m24thizman2-fo-csdap 10592thpym-tetradi-mes-betainyl10642bhs-edian2-ocho-betapy 10593mam2py-24thiz-mes-betadcph10643mam2py-dis-napo-zdabs 10594impy-pipa-eoco-betadcph10644pyrhs-ams3-napo-betadcph 10595imhs-propn-5pho-asppha10645bhs-pazin-oem-psdab 10596deam-eta-chexo-asppha10646amim-pyma2-5pho-aspibua 10597bimhs-mepazin-oem-bhsdap10647impy-pymea-peo-zorn 10598imhs-24thizman2-no2-zdap10648nmor-ams2-chexo-bhsdab 10599edothpym-pyma2-cpeo-zdap10649hythpym-tridi-5pho-zdab 10600bimhs-eta-oeto-bphabs10650pippy-diphmem-pheo-betainyl 106012py-diaz-oem-asppha10651am2py-dis-hso-dfzdap 10602pippy-25oxman2-cno-tsdap10652am2py-pipmea-emo-bnsdap 10603cl3pyme-25oxman2-oeto-10653ibhs-eta-fo-glubzla

glyzdap10654pyraz-amo2-mes-zdap 10604bim-tetradi-cpeo-zdabs10655nim-m24thiman2-meteto-psdap 10605pyr-am2-sem-nbetapy10656imhs-amn2-meo-psdab 10606menim-24thiman-mes-glyzdap10657imhs-amn3-men-betainyl 10607impy-2pazin-5pho-csdap10658me2py-am3-oem-nbetameph 10608bim-m24oxman2-napo-asppha10659bhs-edian2-5pho-zdap 10609dhim-tetradi-no1-zorn10660bim-24thiman2-mommo-glupha 10610prhs-ams3-meo-bnsdap10661edothpym-pnymea-no1-aspibua 10611mam2py-dimephmep-ocho-bhsdap10662menim-edian2-meo-bhsdab 10612impy-25oxman2-meo-zdab10663bhs-amo3-cno-zdab 10613am2py-dimephmem-pyo-betainyl10664impy-edian2-ocho-psdap 10614pippy-pipmea-napo-zdap10665bim-pymea-5pho-betapy 10615me2py-eta-fo-osdap106662pmhs-pazin-pheo-asppha 10616mam2py-24oxman2-meo-bhsdab10667dhim-dis-mes-zdap 10617impy-din-baeo-zdap10668bhs-m24thizman2-5amo-bsdap 10618npip-mepipe-aco-bnsdap10669impy-edia2-oem-nbeta34- 10619pyrhs-pnymea-men-osdapdimeoph 10620amthiaz-tridi-fo-mezphe10670bhs-m25thiz-eoco-tsdap 10621amim-pymea-no1-oxal10671hythpym-ams2-no1-zdabs 10622impy-tetradi-no1-ppsdap10672me2py-dis-imo-mezphe 10623n2py-24thizman2-5pho-10673me2py-n2nme2n-no2-bsdap

betainyl10674bhs-dimephmep-pyo-bnsdap 106242py-din-chexo-bnsdap10675pippy-pazin-mommo-asppha 10625nmhs-pipa-emo-glupha10676bim-amn2-eoco-zdab 10626mam2py-dimephmep-no2-bphabs10677chhs-ams2-baeo-bnsdap 10627nmor-m24thizman2-ocho-mezphe10678imhs-edian2-no1-psdap 10628thpym-pazin-oem-bhsdap10679thpym-eta-5pho-psdap 10629bim-pazin-meo-bhsdap10680chhs-pazin-5amo-mezphe 10681dmam-amo2-men-bnsdap107322py-mepipe-oem-betapy 10682im-diaz-fo-zdab10733imhs-mepipe-ocho-bhsdap 10683imhs-eta-no2-zdap10734deam-amo2-5pho-zdap 10684thpym-eta-eoco-zdab10735thpym-tridi-men-csdap 10685ec-24thizman2-eoco-zdab10736mam2py-pnymea-oem-psdab 10686dhim-mea-oem-zdab10737imhs-diphmep-mes-zdab 10687am2py-diphmem-mes-dfzdap10738gua-24thiman-chexo-aspbzla 10688bhs-dimephmep-chexo-dfzdap107392py-n2nme2n-eoco-zdabs 10689im-24thizman2-men-bphabs10740bhs-eta2s-eoco-glyzdap 10690thpym-mepipe-ocho-psdab10741ibhs-24thizman2-meo-psdapee 10691thpym-amn2-paco-bphabs10742morhs-amo2-men-bhsdab 10692thpym-pazin-no2-bnsdap10743impy-thizn-men-csdap 10693nmhs-pipmea-pheo-aspbzla10744hythpym-pyma2-hso-aspaba 10694hythpym-diphmep-fo-bnsdap107452pmhs-pazi2n-no1-betaet 10695ibhs-diphmep-5amo-aspbzla10746dhim-25oxman2-meo-betadcph 10696am2py-edia2-oem-nbetapy107472pmhs-pazi2n-4pho-zdabs 10697bhs-m24thiz-imo-betainyl10748imhs-24thizman2-5amo-bphabs 10698amthiaz-edian2-5amo-psdap10749ibhs-amo2-4pho-zlys 10699me-pnymea-oem-bhsdab10750fthpym-pipa-oem-bhsdab 10700prhs-tridi-cpro-bhsdab10751mam2py-mepipen2-emo-aspbzla 10701bim-mepipe-hso-aspibua10752pyr-dimephmep-fo-aspbzla 10702imhs-edian2-meo-psdap10753me2py-diphmep-5amo-thizzdap 10703imhs-mepipe-mes-bsdap10754tolhs-mepazin-meto-aspibua 10704mam2py-24thiz-ocho-zdab10755thpym-pyma2-emo-aspibua 107052py-edian2-no1-bnsdap10756pyraz-m24oxman2-oem-mezphe 10706amthiaz-amo2-chexo-dfzdap10757moegua-mepipen2-no2-bhsdap 10707tolhs-mepipen2-mecpo-asppha10758bimhs-ams2-men-zdap 10708hythpym-din-ocho-bnsdap10759im-pnymea-emo-zdab 10709bhs-n2o2n-ocho-psdap10760bhs-am2-oem-nbetabnaphth 10710bim-am3-sem-nzdap10761deam-eta-5pho-aspibua 107112py-amo2-mes-zdab10762bim-m24thiz-men-mezphe 10712thpym-mepipen2-4amo-psdab10763dmthpym-n2o2n-ocho-bhsdap 10713bhs-24thizman2-no1-aspbzla10764impy-pyma2-pheo-glubzla 10714me2py-dipch-mmen-ibsdap10765pyraz-ms-fo-zdabs 10715dhim-pnymea-cpro-psdap10766am2py-dimephmem-nmo-zdabs 10716menim-24thizman2-5amo-10767pyr-tetradi-eoco-bphabs

aspibua10768impy-din-cpro-bhsdab 10717bim-pazin-no2-psdab10769pyr-dimephmep-chexo-glupha 10718mam2py-dimephmem-napo-zdabs10770mam2py-mepipe-ocho-betadcph 10719dmbim-ams2-imo-psdap10771phpip-m25oxman2-men-betadcph 10720am2py-diphmem-5pho-zdapee10772mepip-indan2-5amo-asppha 10721pippy-tetradi-chexo-mezphe10773thpym-pipmea-meo-asppha 10722thpym-edian2-no1-betapy10774pippy-dimen-eoco-asppha 10723pyrhs-pazin-chexo-asppha10775chmhs-amo2-no1-osdap 10724piraz-mepazin-napo-bsdap107762py-eta-mes-zdab 10725amim-pazin-no1-zdabs10777bim-amn2-mes-bhsdap 10726hythpym-24thiz-imo-dfzdap10778morhs-amn2-pyo-bhsdap 10727nim-ams3-5amo-betapy10779bhs-m24oxman2-oem-zdap 10728thpym-mepipe-mes-bnsdap10780dmam-mea-chexo-psdap 10729me-24thiz-mmen-mezphe10781dhim-mea-meteto-ppsdap 10730me2py-pyma2-5pho-aspbzla10782imhs-pymea-imo-betadcph 10731am2py-dimen-oem-zdap10783mam2py-mepipe2-sem-nzdap 10784piraz-diphmep-eoco-glyzdap108342py-pazin-oem-psdab 10785am-dimephmem-5pho-aspbzla10835cl3pyme-diphmep-napo-tsdap 10786dpam-24thizman2-ocho-bnsdap10836im-pazin-pheo-betadcph 107872py-tetras-cpro-bphabs10837thpym-pazin-hso-mezphe 10788imhs-pazin-no1-zdap10838imhs-dimephmem-pyo-dfzdap 10789mam2py-dimeph-mem-chexo-zlys10839hythpym-m25thiz-imo-glyzdap 10790me2py-pazin-emo-aspibua10840morhs-am3diaz-meo-asppha 10791thpym-indan2-aco-zdabs10841amthiaz-dio-meto-csdap 10792me2py-trias-no2-mezphe10842amim-diphmep-imo-psdapee 10793morhs-mepazin-ocho-dfzdap10843imhs-mea-chexo-psdap 10794dhim-dio-no2-aspibua10844dhim-mepazin-5pho-aspibua 10795bim-amo2-ocho-zdabs10845tolhs-24thiz-no1-betadcph 10796imhs-m24oxman2-meo-osdap10846amim-edian2-fo-bphabs 10797piraz-ams2-eoco-ibsdap10847mam2py-mepipe2-sem-nzdab 10798thpym-diphmep-cpeo-betadcph10848pippy-m25thiz-mommo-psdap 10799piraz-dimephmep-meteto-10849mam2py-pentas-5amo-psdap

glyzdap10850piraz-propn-5pho-dfzdap 10800pippy-pentadi-emo-bnsdap10851imhs-diphmep-oem-zdabs 10801bhs-eta-4amo-bnsdap10852mam2py-dimen-oem-zdab 10802bimhs-tridi-meo-bsdap10853bzl-tridi-fo-bhsdab 10803thpym-25oxman2-meteto-psdab10854dmthpym-pymea-men-betainyl 10804bim-ams2-no2-aspbzla108552py-am3-oem-nbetameph 10805bhs-pazin-oem-bnsdap10856bimhs-pymea-mes-aspibua 10806bhs-amn2-mes-betapy10857amim-m24thiz-oem-psdap 10807imhs-amn2-eoco-betapy10858hythpym-propn-meo-bhsdap 10808am2py-edian2-pro-psdab108592py-edian2-5pho-psdab 10809menim-tetradi-cpro-aspibua10860thpym-eta-ocho-bsdap 10810impy-m25thiz-4amo-aspaba10861imhs-diphmep-napo-psdab 10811bimhs-24thiz-ocho-bnsdap10862me2py-thizn-chexo-zdabs 10812edothpym-amn2-pyo-bsdap10863thpym-dio-men-glubzla 10813me2py-pazin-mommo-zdap10864imhs-amn2-no2-zdap 10814hythpym-25oxman2-chexo-10865morhs-pipmea-4amo-aval

mezphe10866mam2py-edia2-oem-nbeta34- 10815n2py-25oxman2-men-zdabsdimeoph 10816pyr-m24thizman2-imo-betadcph10867ec-mepipen2-napo-bnsdap 10817dhim-am3-oem-nbetameph10868deam-edian2-5amo-bhsdab 10818tolhs-dimen-mes-aval108692py-mepipe-meo-bnsdap 10819bimhs-m25thiz-ocho-asppha108702py-tridi-5pho-glubzla 10820am2py-mepipe2-oem-npsdap10871mam2py-amn3-5amo-aspibua 10821amim-edian2-5amo-glyzdap10872bim-pyma2-napo-zdab 10822dhim-dimephmem-men-psdab10873am2py-pazin-mes-bnsdap 10823dhim-edian2-5amo-bsdap10874dpam-indan2-cnmo-aspibua 10824pippy-am2-sem-nzdap10875nim-24thizman2-chexo-bphabs 10825am2py-diphmep-fo-mezphe10876amim-pymea-aco-bhsdap 10826thpym-mepipe-mmen-betapy10877hythpym-dis-no1-betapy 10827phpip-mepazin-no1-bphabs10878impy-pyma2-emo-bphabs 108282py-eta-oem-zdab108792py-edian2-5pho-bsdap 10829mam2py-tetras-meo-betapy10880amthiaz-mea2s-5pho-mezphe 10830pippy-diphmep-oem-bphabs10881impy-25oxman2-chexo-zdabs 10831am2py-mepipen2-5amo-bsdap10882bimhs-mepipe2-sem-nzdap 10832npip-ams2-eoco-zdap10883imhs-pnymea-no1-betapy 10833pyraz-m25thiz-5amo-bsdap108842py-pipa-mes-betapy 10885pyraz-25oxman2-mecpo-mezphe10936im-amn3-cpeo-bhsdab 10886tolhs-am2-oem-nbetabnaphth10937impy-am3-sem-nzdap 10887bhs-diphmep-meto-bsdap10938bhs-amo3-pro-psdap 10888hythpym-amn3-chexo-bnsdap10939ec-pentas-chexo-aspibua 10889bim-edian2-5pho-psdab109402py-mepipe-mes-bhsdap 10890bim-25oxman2-fo-psdab10941me2py-thizn-imo-bhsdap 10891imhs-pipa-cpeo-psdap109424pmhs-edian2-ocho-bnsdap 10892thpym-mepipe-oem-betapy10943dmbim-am3diaz-no1-bphabs 10893me2py-24thizman2-paco-bsdap10944mam2py-3diaz-no2-bphabs 10894edothpym-pentadi-baeo-psdap10945emnim-24thizman2-fo-zdap 10895gua-pipmeo-mommo-zdabs10946bim-mepipe-eoco-bsdap 10896chmhs-props-5amo-bphabs10947bimhs-mepipe-emo-thizzdap 10897bhs-tridi-oeto-thizzdap10948piraz-trias-peo-asppha 10898im-tridi-men-psdab10949dhim-3pazin-imo-mezphe 108992py-mepipe-ocho-psdab10950me2py-amn3-baeo-bhsdap 10900pyraz-tridi-eoco-zdab10951am4py-pazin-emo-zdap 10901hythpym-diphmep-emo-psdap10952bhs-amn2-no1-bsdap 10902nmor-pazin-cpeo-aspaba10953imhs-mepipe-mes-betapy 10903bzl-eta-meteto-asppha10954am4py-din-mes-betaet 10904tolhs-pipmeo-mes-zdab10955bhs-eta-oem-betainyl 10905bimhs-dimen-oem-asppha10956dhim-dis-4amo-zdabs 10906thpym-pnymea-no1-zdabs10957phpip-dimephmem-cnmo-psdab 10907bimhs-mepipen2-baeo-tsdap109582py-tetradi-5amo-tsdap 10908me2py-mepipen2-ocho-betadcph10959bim-props-men-zdab 109092py-eta-eoco-zdab10960me2py-pentas-emo-bsdap 10910pippy-dimen-men-psdapee10961mepip-am3diaz-meteto-bhsdap 10911imhs-25oxman2-napo-zdabs10962dmam-dipch-mmen-bphabs 10912hythpym-m24thizman2-4amo-10963hythpym-eta-oem-psdap

asppha10964pyrhs-mepipe2-sem-nbeta34- 10913imhs-eta-no2-zdabdimeoph 10914am4py-mepipen2-ocho-zdabs10965bz-mepipe2-sem-nbetameph 10915thpym-3diaz-5amo-bsdap10966fthpym-m24thizman2-eoco- 10916piraz-amn2-oem-betadcphbetapy 10917n2py-dimephmep-no1-betainyl10967nmor-din-no2-betainyl 10918menim-n2o2n-baeo-betadcph10968nmhs-diphmep-5pho-zdab 10919n2py-tridi-no2-ppsdap10969pippy-dimen-napo-aval 10920me2py-trias-5pho-betadcph10970pyrhs-am3-sem-nbetameph 109212py-m25oxman2-no1-bhsdap10971bz-din-5amo-bnsdap 10922dhim-ams2-eoco-asppha10972pippy-3pazin-emo-bsdap 10923pippy-edian2-oem-bsdap10973bimhs-pazin-5pho-mezphe 10924imhs-amn3-pheo-bphabs10974dmbim-amn2-napo-mezphe 10925gua-dimephmep-mommo-bphabs10975bim-trias-emo-aspbzla 10926piraz-edian2-daco-tsdap10976piraz-amo2-emo-betadcph 10927emnim-amn2-no2-glyzdap10977npip-diphmep-no2-zdabs 10928mepip-24thiz-4amo-bsdap10978bim-thizs-napo-dfzdap 109292py-amn3-5pho-bsdap10979me2py-trias-imo-glyzdap 10930bimhs-pipa-cpro-aspibua10980pyraz-25oxman2-napo-bnsdap 10931chmhs-dimephmep-meo-bnsdap10981chhs-dis-eoco-betadcph 10932hythpym-n2o2n-imo-betainyl10982imhs-amn2-meo-zdab 10933bimhs-am2-sem-nzdap10983imhs-ams2-5amo-bsdap 10934pippy-ams3-no2-asppha10984mam2py-amn2-napo-betadcph 10935hythpym-ams2-5amo-csdap10985mam2py-n24thiman-no2-aspibua 10986am4py-pymea-aco-zdap11038mam2py-mepipen2-napo-psdap 10987mam2py-eta-chexo-bhsdap11039bhs-eta-5pho-zdab 109882py-din-meo-thizzdap11040me-tetradi-5pho-zdab 10989thpym-pazin-fo-bhsdab11041ec-24thiz-napo-bsdap 10990morhs-pnymea-emo-betadcph11042imhs-ams2-no2-glyzdap 10991fthpym-eta-hso-betadcph11043edothpym-25oxman2- 10992dpam-pipa-oem-tsdapnapo-bhsdap 109932pmhs-pipmes-men-zlys11044imhs-eta-eoco-psdab 10994pippy-tridi-napo-mezphe11045imhs-dimephmep-mes-zdabs 10995z-edian2-eoco-betadcph11046bim-pymea-mes-glyzdap 10996imhs-m25oxman2-5pho-betapy11047bhs-amo2-men-ppsdap 10997pippy-amo2-pro-csdap11048bim-mepipen2-fo-glupha 10998bimhs-amn2-napo-betapy11049menim-amo3-napo-betadcph 10999am4py-m24thiman2-5amo-zlys11050bhs-edian2-no1-bhsdap 11000morhs-24thizman2-meo-asppha11051amim-diphmep-no1-bhsdab 110014pmhs-am3-sem-nbetapy11052bhs-edian2-napo-zdap 11002mepip-m25thiz-ocho-bhsdap11053am2py-pentas-men-psdap 11003impy-propn-mmen-zdab11054thpym-eta-oem-psdap 11004imhs-eta-men-bhsdap11055fthpym-pazin-emo-csdap 11005ec-edian2-nmo-dfzdap11056imhs-pipa-chexo-betapy 11006pippy-dimephmem-ocho-bnsdap11057pyraz-pnymea-mes-aspbzla 11007prhs-mepipen2-fo-dfzdap11058mam2py-pazin-meto-mezphe 11008thpym-pipa-aco-bsdap11059ec-24thiman2-emo-bphabs 11009pippy-trias-5pho-aspbzla11060bhs-amn2-no2-psdap 11010dhim-mepipe-eoco-aval11061ibhs-m24thizman2-meo-bhsdap 11011pippy-dimen-eoco-bnsdap11062imhs-eta-eoco-zdab 11012mam2py-tridi-eoco-dfzdap11063bhs-mepipe-5pho-betapy 11013pyraz-pyma2-imo-psdab11064impy-am3-oem-nbeta34dimeoph 11014bimhs-am3-sem-nbetapy11065am2py-diphmep-cpro-zdap 11015ec-trias-ocho-bphabs11066me2py-n2o2n-fo-psdab 11016bimhs-24thiz-fo-aspbzla11067piraz-25oxman2-meo-bnsdap 11017menim-dis-oem-aspbzla11068morhs-25thizman2-nmo-asppha 11018tolhs-thizs-ocho-bhsdab11069pyraz-24thiz-5pho-zdap 11019imhs-pymea-no2-aspaba11070pyrhs-em2-sem-nbetameph 11020dhim-pazin-men-bhsdab11071prhs-edian2-emo-glyzdap 11021dhim-amn3-eoco-asppha11072dmthpym-pipmeo-mes-betapy 11022am2py-edian2-meo-psdab11073piraz-24thiz-5pho-bnsdap 11023pippy-pipmea-no1-psdab11074pippy-tetradi-oem-mezphe 11024bimhs-mepipen2-emo-zdap11075deam-am2-sem-nzdab 11025me2py-ams3-cnmo-aspaba11076bhs-mepipe-mecpo-bnsdap 11026thpym-eta-5pho-bnsdap11077amim-2pazin-baeo-bhsdap 11027nmor-pipa-oem-mezphe11078n2py-eta-emo-betainyl 11028fthpym-amn2-cpeo-bphabs11079chmhs-tetradi-aco-tsdap 11029bimhs-mepipen2-meto-betadcph11080chhs-24thiz-mecpo-zdabs 11030bz-eta-fo-mezphe11081phpip-props-mecpo-betadcph 11031thpym-mepazin-chexo-betapy11082me2py-pnymea-eoco-mezphe 11032thpym-edian2-mes-bnsdap11083dmbim-m24thizman2-peo- 11033bhs-am3diaz-oem-bnsdapbetadcph 11034amim-mea-mes-csdap11084im-25oxman2-fo-betapy 11035morhs-tetradi-no2-glubzla11085pippy-pyma2-emo-bhsdab 11036mam2py-m25thiz-cno-psdap11086bimhs-ms-hso-asppha 11037gua-am3-oem-nzdab11087imhs-trias-cno-glyzdap 11088dhim-am3diaz-emo-bhsdab11139ec-pipmea-meo-bphabs 110892py-trias-men-betaet111402py-thizn-5pho-betainyl 11090amim-pipa-5pho-bhsdab11141imhs-mepipe-mes-zdap 11091pippy-amn2-no2-zdab11142thpym-24thiman-eoco-bnsdap 11092npip-pipmea-meteto-zlys11143am2py-mepipe-men-aspbzla 11093dhim-pymea-mes-csdap11144bhs-dimephmem-men-glyzdap 11094emnim-pymea-men-thizzdap111452py-mepipe-no1-psdab 11095nmhs-m25oxman2-emo-psdap11146dhim-pipmeo-ocho-asppha 11096thpym-diphmem-no1-bsdap11147bimhs-mepipe2-oem-nbetab 11097mam2py-eta-imo-aspphanaphth 11098bim-amo2-mes-bnsdap11148bim-dimen-no2-bsdap 11099amim-propa2s-mes-betadcph11149bim-tetradi-mes-betadcph 11100mam2py-din-hso-glubzla11150dpam-24thizman2-ocho-bhsdab 111012py-25oxman2-no1-zdap11151impy-dimephmep-chexo-aspbzla 11102bimhs-amn2-men-psdab11152menim-mepipen2-meo-betadcph 11103bimhs-dimen-ocho-oxal11153pippy-trias-oeto-zdap 11104imhs-edian2-no2-bsdap111542py-eta-no1-zdabs 11105me2py-m25thizman2-no1-csdap11155bim-m25thizman2-pheo-zdap 11106impy-din-no1-zdabs111562py-25oxman2-no2-psdab 11107moegua-dimephmep-men-bhsdap11157bimhs-diphmem-no2-zorn 11108amim-mepipe2-oem-nzdab11158bhs-mepipen2-daco-zdabs 11109imhs-diphmem-emo-mezphe11159pyraz-diphmep-5amo-psdab 11110thpym-pnymea-fo-glyzdap11160mepip-mepipe2-oem-nbeta34- 11111thpym-din-5amo-betapydimeoph 11112emnim-pymea-men-glyzdap11161am2py-25oxman2-mes-psdab 11113bhs-amn2-5pho-bsdap11162dhim-dimephmem-5pho-csdap 11114me2py-am3-sem-nzdab11163bhs-diphmem-men-bhsdap 11115dhim-pnymea-men-psdab11164bhs-dimephmep-no1-bnsdap 11116bim-m24thizman2-men-mezphe11165bhs-m24oxman2-ocho-zdabs 11117amim-amo2-no1-psdab11166prhs-dis-chexo-bnsdap 11118piraz-dimephmep-ocho-11167mam2py-eta-meo-aspbzla

betainyl11168am2py-amn2-men-glyzdap 11119me2py-edian2-meo-bsdap11169hythpym-pazin-napo-csdap 11120menim-pipmea-5pho-bsdap111702py-edian2-meo-bhsdap 11121me2py-m25thiz-peo-aspibua111712py-mea-napo-aspaba 11122thpym-eta-men-asppha11172mam2py-tetradi-imo-csdap 11123bhs-pnymea-fo-bhsdap11173im-pnymea-5amo-betapy 11124nmor-mepipe-no1-bnsdap11174emnim-diphmem-no1-betaet 11125phpip-dimen-chexo-betaet11175me2py-props-nmo-tsdap 11126bim-dis-chexo-dfzdap11176piraz-pnymea-oem-betadcph 111272py-mepipe-eoco-betapy11177emnim-pnymea-mmen-betapy 111282py-dimephmep-4amo-bhsdap11178mepip-amn2-oem-betainyl 11129amim-24thiz-aco-dfzdap11179dhim-amn3-aco-bnsdap 111302py-amn2-eoco-zdap11180hythpym-25thiman2-oem- 11131chhs-m25thiz-meo-psdapeeaspibua 11132pyrhs-mepipen2-cno-bsdap11181dhim-pazin-cnmo-mezphe 11133menim-25thiman2-5amo-aspibua111822py-thizs-imo-zdapee 111342py-dimen-aco-bsdap11183imhs-mepipe-no1-bnsdap 11135hythpym-thizn-emo-csdap11184impy-tridi-mommo-oxal 11136bim-pazin-no1-bhsdap11185a-mim-diphmep-men-zdab 11137hythpym-pnymea-imo-bnsdap11186thpym-amn2-ocho-zdab 11138bim-amn2-no1-bnsdap11187nmor-propa2s-mes-aspibua 11188emnim-m25thiz-aco-zdapee11238piraz-m25thiman2-chexo-zdap 11189am2py-dimephmep-mes-betadcph11239ec-pymea-no1-aval 11190moegua-mepipe-daco-dfzdap11240dmbim-ams2-men-glupha 111912py-edian2-nmo-zdab112412py-pnymea-napo-zdap 11192thpym-butn-mommo-psdapee11242impy-amo2-chexo-glupha 11193thpym-eta-oem-asppha112432py-thizs-no2-bphabs 11194ibhs-pymea-meo-csdap11244cl3pyme-24thizman2- 11195thpym-mepipe-mes-zdab5amo-glyzdap 11196mepip-diphmep-mes-ibsdap11245piraz-pazin-emo-glupha 11197dhim-m25thiz-napo-zlys11246bimhs-trias-eoco-bphabs 11198pippy-mepipen2-eoco-zdap112472py-butn-fo-aspbzla 11199pyrhs-am2-sem-nbetabnaphth11248me2py-pyma2-men-betapy 11200nmor-tridi-napo-zdap11249bim-mepazin-5amo-zdap 11201imhs-edian2-mmen-psdapee11250bim-edian2-meo-zdap 11202chhs-mepipe-oem-thizzdap11251imhs-amo2-cno-glyzdap 11203impy-pazin-no1-betapy11252thpym-m24thiz-emo-betainyl 11204pippy-amn3-peo-psdab11253hythpym-pipa-cnmo-zdab 11205pippy-dimephmem-oem-zdap11254pippy-eta-imo-thizzdap 11206emnim-amn2-5amo-betapy11255bhs-24thiz-fo-glyzdap 11207piraz-3diaz-paco-csdap11256bhs-amn2-ocho-psdab 11208dmbim-amn2-mes-aspaba11257chmhs-mepazin-meo-aspbzla 11209bim-pnymea-fo-betainyl11258nmhs-thizn-chexo-glyzdap 11210c13pyme-25oxman2-eoco-11259imhs-amn2-meto-mezphe

aspbzla11260thpym-eta-no1-bsdap 11211moegua-tetras-ocho-mezphe112612py-eta-5pho-bnsdap 11212mepip-pipmeo-4amo-bhsdap11262me2py-eta-oeto-mezphe 11213bim-dis-men-aspaba11263fthpym-dimen-no1-psdap 11214ppy-pipmea-eoco-bnsdap11264me-24thiman-chexo-glyzdap 11215pyraz-edian2-napo-psdab11265pippy-dis-ocho-asppha 11216hythpym-24thiman2-meto-zdap11266chhs-m24thizman2-men-aspibua 11217pippy-amn2-meo-bhsdab11267am-tetradi-baeo-glubzla 11218dpam-mea2s-aco-glyzdap11268thpym-edia2-sem-nbeta34- 112192py-thizo-cnmo-bnsdapdimeoph 11220bim-tetradi-meo-asppha11269thpym-eta-meo-zdab 11221pippy-pazin-chexo-bhsdab11270nmhs-24thizman2-no1-mezphe 11222emnim-diphmep-chexo-zdabs11271bim-3diaz-oem-bhsdap 11223imhs-m24thiman2-meo-csdap11272prhs-edian2-pyo-csdap 11224bimhs-mepipen2-napo-tsdap11273pippy-25oxman2-no1-dfzdap 11225imhs-25thiman2-no1-bnsdap11274gua-dimen-meo-psdapee 11226thpym-m25thizman2-chexo-11275thpym-dis-mes-zdab

bnsdap11276am2py-pyma2-men-betainyl 11227ppy-ams2-oeto-csdap11277impy-dimephmep-cpro-bnsdap 11228dhim-tetradi-meto-glyzdap11278bhs-mepipe2-sem-nbeta3- 11229bimhs-mea-imo-bphabs4dimeoph 11230bhs-25oxman2-napo-betainyl11279amim-pipa-oeto-csdap 11231pyr-dimephmem-napo-psdap11280chhs-propn-emo-bhsdap 11232dmthpym-pentadi-5amo-mezphe11281me2py-pymea-chexo-psdap 11233dmam-indan2-cpro-psdab11282bhs-mepipe-ocho-zdabs 11234im-eta2s-eoco-bhsdab112832pmhs-m25oxman2-5amo-bphabs 11235dhim-butn-mes-osdap11284moegua-pazin-mes-zdap 11236impy-pentas-oem-aspbzla11285bhs-24thiman2-no1-osdap 11237imhs-mepipe-oem-zdab11286me-m25thiz-5pho-psdap 11287me2py-diphmem-imo-bsdap11339impy-pyma2-oem-ibsdap 11288chmhs-tridi-5amo-aval11340am2py-mepipe-4pho-osdap 112892py-mepipe-meo-bhsdap11341pippy-diphmem-men-betapy 11290impy-amo2-napo-zdabs11342dhim-indan2-fo-mezphe 11291pyrhs-diphmep-imo-zdap11343imhs-mepipe-no1-zdap 11292am-din-no1-csdap11344ec-tetradi-5amo-mezphe 11293thpym-amn3-no1-csdap11345mam2py-m24thizman2-mes-zdap 112942py-eta-ocho-bnsdap11346bzl-amn2-paco-psdab 11295thpym-pymea-ocho-asppha11347bhs-tetras-daco-betapy 11296chhs-propn-no2-aspbzla11348pyrhs-24thiman-imo-betapy 11297thpym-amnn2-oem-bsdap11349me-diphmem-eoco-aspaba 11298hythpym-tridi-cno-aspbzla11350bim-pyma2-eoco-aspbzla 11299menim-m24thiman2-emo-zdap11351bim-edian2-oem-zdab 11300hythpym-tridi-fo-glyzdap11352chhs-eta-meto-betainyl 113012py-amn3-emo-psdab11353bimhs-propn-peo-csdap 11302bimhs-amo2-no2-aspbzla11354n2py-m24thizman2-5pho-betapy 11303me2py-amn2-men-zdap11355dmbim-24oxman2-men-ppsdap 11304mam2py-indan2-5amo-zorn11356bhs-amn2-ocho-zdap 11305piraz-tetras-no2-aspbzla11357bimhs-mepipe2-oem-npsdap 11306dhim-ams2-imo-aspbzla11358dhim-trias-meo-bnsdap 11307moegua-propn-men-dfzdap11359bim-amn3-oem-betapy 11308bhs-mea-no2-bphabs113602py-tridi-mes-aspbzla 11309piraz-dio-emo-mezphe11361dhim-amn3-5pho-betadcph 11310bim-edia2-sem-npsdap11362dhim-pazin-chexo-ppsdap 11311thpym-edian2-napo-aspbzla11363prhs-tridi-mes-bphabs 11312thpym-amn3-meteto-zdabs11364dmam-propn-oem-thizzdap 11313bz-25oxman2-meo-tsdap11365bimhs-diphmem-nmo-betainyl 11314am2py-pymea-oem-csdap11366imhs-props-chexo-oxal 11315thpym-eta-no2-psdap11367imhs-thizn-napo-bsdap 11316bim-amn2-cnmo-psdab11368bhs-eta-meo-bsdap 11317thpym-eta-meo-zdap11369amim-mepipen2-emo-betapy 113182pmhs-diphmem-emo-mezphe11370thpym-ms-men-bnsdap 11319imhs-25oxman2-imo-bsdap113712py-pipa-imo-glyzdap 11320bimhs-propa2s-fo-csdap11372imhs-diphmep-5amo-betapy 11321phpip-thizn-pyo-aval11373dmbim-25thizman2-emo-bhsdap 11322pippy-amo2-meo-bphabs11374emnim-mepazin-eoco-zdabs 11323bhs-eta-no1-psdab11375imhs-tetradi-meo-bphabs 11324pippy-am3-sem-nbetabnaphth113762py-eta-eoco-psdab 11325mam2py-pyma2-napo-betainyl11377moegua-tetradi-meto-bphabs 11326pippy-dich-eoco-bhsdap11378z-dimephmem-5amo-betadcph 11327impy-24thizman2-cpro-psdap11379thpym-eta-5pho-zdap 11328bim-amo2-paco-bnsdap11380bim-amn2-meo-psdap 11329amim-2pazin-aco-mezphe11381dhim-diphmem-imo-betainyl 11330n2py-24thiz-cno-bnsdap11382bimhs-m25oxman2-emo-bsdap 11331thpym-ams2-imo-csdap11383chhs-tetradi-peo-psdap 11332bhs-amn3-imo-zdabs11384piraz-propa2s-fo-bnsdap 11333pippy-edian2-5pho-bphabs11385mepip-mepazin-fo-bhsdap 11334pippy-thizs-5amo-asppha11386pippy-dimen-baeo-bhsdab 11335amim-thizs-meteto-glupha11387amim-pipa-emo-psdap 113362py-24thiman-no2-bsdap11388dpam-mepipe-men-bsdap 11337bim-mepipe-5pho-psdap11389bhs-butn-mmen-bhsdap 11338prhs-indan2-ocho-aspibua11390morhs-diphmep-cno-bnsdap 11391thpym-pazin-oem-psdap11441mam2py-am2-oem-nbeta34- 11392imhs-pazin-5pho-bsdapdimeoph 11393moegua-ams2-napo-zdabs11442im-pazin-fo-bhsdap 11394bhs-24thiz-fo-thizzdap11443am2py-amn2-meo-bhsdab 11395bhs-din-emo-mezphe11444mam2py-amn3-mes-betaet 11396am2py-dimen-ocho-csdap11445impy-n2o2n-cno-bsdap 11397nmhs-mepipe-5pho-aspbzla11446imhs-trias-no1-bhsdap 11398pyr-eta-paco-bnsdap11447mam2py-pymea-ocho-bhsdap 11399imhs-dimephmep-oem-csdap11448amim-24thizman2-peo-bhsdab 11400me2py-mepipen2-ocho-betadcph114492py-amn2-5amo-glubzla 11401bim-amn2-no2-psdab11450bzl-mepazin-meo-aspbzla 11402bim-mepipe-no1-psdab11451amthiaz-pazin-men-betapy 11403pippy-pnymea-5amo-bhsdab11452dhim-amn3-5pho-betadcph 11404am2py-24thizman2-oem-bnsdap11453gua-dimen-napo-betapy 11405amim-pipa-4amo-aspibua11454pippy-amo2-meto-betadcph 11406dpam-25oxman2-men-mezphe11455amim-dimen-men-csdap 11407piraz-dimephmep-no1-betapy11456bimhs-m25thizman2-eoco- 11408impy-24thiz-chexo-glyzdapdfzdap 11409hythpym-pnymea-paco-zorn11457me2py-pnymea-paco-dfzdap 11410mam2py-pipa-eoco-csdap11458amim-pyma2-5amo-dfzdap 11411piraz-mepipe-emo-bphabs11459dhim-ams2-meo-bsdap 11412deam-ams2-napo-betapy11460bimhs-m24thizman2-mes-oxal 11413n2py-pnymea-chexo-betainyl11461bim-am2-sem-nbetabnaphth 11414me2py-propn-emo-asppha11462bhs-pazin-eoco-bhsdap 11415am2py-m24thizman2-pheo-11463dmam-thizn-nmo-bhsdab

aspbzla11464impy-ams2-chexo-asppha 11416bim-dimephmep-ocho-zdapee11465bzl-ams3-meo-psdap 11417bzl-thizn-no1-thizzdap114662py-24thizman2-mmen-csdap 11418dpam-pipmes-no1-betainyl11467nmor-diphmem-oem-mezphe 11419pyr-tridi-chexo-psdab11468ec-tetradi-eoco-betapy 11420dhim-pymea-5pho-aspibua11469bzl-eta2s-meo-bnsdap 11421bimhs-24thizman2-fo-aspibua11470pyrhs-pazi2n-no1-zdab 11422impy-eta-ocho-bhsdap11471me2py-pentas-mes-mezphe 11423prhs-n24thiman-aco-aspibua11472nim-pymea-oeto-tsdap 11424am2py-pipmea-imo-betapy11473imhs-mepipe-oem-zorn 11425nim-pentas-emo-psdap11474thpym-eta-eoco-psdap 11426amim-pipmea-emo-zdab114752py-pazin-oem-zdab 11427me2py-pipa-chexo-dfzdap11476imhs-24thiz-meo-aspbzla 11428am4py-thizn-men-bsdap11477ibhs-mepipe-mes-bhsdab 11429pippy-indan2-oeto-zdabs11478fthpym-dimen-oem-mezphe 11430amim-amo2-baeo-bsdap11479dpam-ams2-meo-aspaba 11431impy-amn2-5amo-psdab11480phhs-edian2-eoco-psdap 11432amim-mepipen2-peo-zdap11481dpam-mea-mes-bsdap 11433bzl-hexas-emo-bsdap11482bhs-tetradi-5amo-glyzdap 11434bim-pnymea-chexo-bsdap11483me2py-tridi-ocho-bhsdap 11435dmam-25thiman2-meo-betapy11484thpym-diphmem-5pho-aspaba 11436pippy-diphmep-meo-bsdap11485menim-amo2-pyo-dfzdap 11437cl3pyme-diphmep-no2-zdab11486dhim-m25thiz-imo-psdab 114382py-amn2-mes-bnsdap11487imhs-diphmem-oem-betadcph 11439dmbim-m24thiz-meo-mezphe11488nim-m24thizman2-eoco-aspibua 11440ppy-dimephmep-5amo-dfzdap11489imhs-amo2-pyo-aspbzla 11490dhim-24thiman2-chexo-psdap11540mam2py-24thizman2-baeo- 11491bhs-pazin-no2-psdabbetainyl 11492bhs-edian2-5pho-bsdap11541thpym-mepipe-no2-betapy 11493edothpym-dio-no2-psdab11542impy-3diaz-eoco-zlys 11494piraz-m24thizman2-meo-zorn11543bim-mea2s-paco-psdab 11495dmam-am3-oem-nbetameph11544amim-hexas-5pho-dfzdap 114962py-m24thizman2-peo-betadcph11545morhs-dimephmep-ocho-csdap 11497imhs-tetradi-napo-zdab115462py-m25thiz-5pho-betapy 11498am2py-amn3-meo-glyzdap11547thpym-diphmep-oem-bnsdap 11499bimhs-tetradi-mes-oxal11548me2py-pipmeo-no2-asppha 11500me2py-indan2-chexo-zdap115494pmhs-edian2-cnmo-csdap 11501impy-ams2-mommo-bphabs11550hythpym-24thizman2-meo- 11502thpym-25oxman2-baeo-aspibuaaspbzla 11503bimhs-trias-hso-mezphe11551piraz-pipa-mes-bnsdap 11504bhs-pnymea-no2-zdab11552piraz-pipmes-chexo-psdab 11505thpym-amn3-ocho-bhsdap11553bim-edian2-no1-bnsdap 11506bimhs-thizn-men-csdap11554bim-mepipe-5pho-bsdap 11507dmthpym-amn3-napo-bphabs11555am4py-pnymea-no1-dfzdap 11508pyrhs-pazi2n-baeo-dfzdap11556bimhs-dis-ocho-zdap 11509amthiaz-pipa-cnmo-bphabs11557thpym-thizn-oeto-asppha 11510imhs-amo2-pro-psdab11558menim-mea-emo-zdabs 11511dmbim-ams2-5amo-glupha11559fthpym-pnymea-peo-aspibua 11512pyrhs-24oxman2-5pho-psdab11560bim-tetras-eoco-bhsdap 11513bim-amo2-5amo-bhsdap11561ec-am2-oem-nbetameph 11514me2py-edian2-mommo-zdabs11562impy-trias-no1-betapy 115152pmhs-24thiz-no1-glyzdap11563thpym-amn2-no2-zdap 11516me2py-eta-mes-dfzdap11564pippy-eta-no2-betainyl 11517moegua-eta-cnmo-aspbzla11565am2py-trias-no1-betadcph 11518am2py-dis-eoco-csdap115662py-25oxman2-imo-betainyl 11519chhs-trias-5pho-mezphe11567impy-thizn-meo-betadcph 11520hythpym-m24thizman2-oem-11568pippy-mepipe-mecpo-psdap

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12000bhs-pazin-no1-psdab12050pippy-eta-fo-aspibua 12001hythpym-mea-meo-thizzdap12051piraz-eta-4amo-bphabs 12002bzl-edia2-sem-nbeta34dimeoph12052pippy-pipa-no2-bsdap 12003bimhs-dis-chexo-csdap12053am2py-dimen-chexo-glubzla 12004nmhs-25thiman2-5pho-bphabs12054am2py-pipmea-pyo-betadcph 120052py-dipch-fo-bsdap12055piraz-dipch-napo-aspibua 12006prhs-mepipen2-eoco-zdab12056gua-pipa-men-psdab 12007imhs-mepipen2-napo-aspbzla12057chmhs-dis-oem-osdap 12008bim-tridi-ocho-asppha12058fthpym-pymea-5pho-zlys 12009phhs-m25thiz-oeto-aspbzla12059piraz-m25oxman2-fo-zdabs 12010mam2py-25oxman2-emo-betapy12060imhs-mepipe-ocho-zdap 12011thpym-eta2s-meo-csdap12061thpym-eta-imo-aspbzla 12012thpym-mepipe2-sem-npsdap12062bhs-amo3-eoco-dfzdap 12013amim-mepazin-pheo-zdabs12063npip-din-cpeo-betainyl 12014impy-amo2-no2-zdab12064me2py-edian2-men-bnsdap 12015pippy-3diaz-mes-betadcph12065bimhs-m24thizman2-mecpo- 12016hythpym-mepipe2-sem-betadcph

nbeta34dimeoph12066piraz-mepipen2-meo-zlys 12017bim-mepipe-emo-psdapee12067edothpym-amn3-daco-zdap 12018imhs-m24thizman2-4amo-12068gua-hexas-mes-csdap

thizzdap12069piraz-dimephmem-mmen-csdap 12019mam2py-24thiz-4pho-betadcph12070am2py-am3-sem-nzdab 12020me-pnymea-mecpo-zdap12071mam2py-pymea-no1-aval 12021ibhs-pnymea-mecpo-psdap12072z-pnymea-5amo-psdap 12022dhim-dis-eoco-zlys12073piraz-amo2-oem-betainyl 12023am2py-pipa-no2-betapy12074am2py-tetras-men-bnsdap 12024tolhs-thizn-mes-aspbzla12075fthpym-3pazin-chexo-bhsdab 12025bhs-m25thiz-pro-zdabs12076piraz-tetradi-men-aspbzla 12026am2py-am2-oem-npsdap12077dhim-pnymea-oem-bhsdab 12027pippy-dimen-pro-glyzdap12078moegua-din-oem-bhsdab 12028bim-edian2-oem-bnsdap12079morhs-mepipe2-oem-npsdap 12029dmthpym-m25thiz-chexo-asppha12080bz-diaz-oem-bnsdap 12030am2py-mepazin-no2-bnsdap12081pyraz-mepipe-men-bphabs 12031bhs-amn2-ocho-bnsdap12082imhs-mepipe-meo-bhsdap 12032amim-24thiman-aco-zdab12083impy-25oxman2-oem-aspbzla 12033thpym-m24thizman2-cno-dfzdap12084amim-diphmem-fo-betapy 12034pippy-24thizman2-mes-psdab12085dmthpym-thizn-4pho-oxal 12035hythpym-edian2-fo-thizzdap12086thpym-n2o2n-no1-zdab 120362py-pnymea-napo-bsdap12087bhs-edian2-meo-bnsdap 12037amim-25oxman2-emo-zdapee12088hythpym-pipa-4pho-psdap 120382py-m25thiz-men-psdapee12089pippy-diaz-fo-tsdap 12039bim-pazin-peo-aspibua12090dhim-dimephmem-paco-zdab 12040me2py-mepipe-ocho-ibsdap12091bhs-pazin-meo-psdab 120412py-eta-men-betainyl12092phhs-24thizman2-imo-bhsdap 12042piraz-dimephmem-chexo-dfzdap12093thpym-dimephmep-men-glyzdap 12043amim-diphmep-5pho-glyzdap12094pippy-edia2-sem-nbeta34- 12044bhs-edian2-5pho-psdabdimeoph 12045amim-dimephmep-paco-betapy11095menim-pazi2n-chexo-mezphe 12046am2py-pipmea-mes-bsdap12096imhs-mepipe-meo-bnsdap 12097nmhs-amo2-imo-thizzdap12146pippy-mepipe-5amo-mezphe 12098phpip-edia2-sem-nbetameph12147piraz-3diaz-cnmo-zdap 12099npip-eta2s-ocho-csdap12148dpam-dimephmem-napo-zdap 12100fthpym-edian2-4amo-aval12149pippy-pazin-men-bphabs 12101am2py-ms-pheo-asppha12150thpym-tridi-men-betadcph 121022py-trias-5pho-aspbzla12151imhs-mepipen2-5pho-aspibua 12103bhs-pazin-eoco-zdab12152am2py-am3-oem-nbetapy 12104impy-mepipe2-sem-nzdap12153dhim-din-mes-psdab 121052py-edian2-no2-bnsdap12154thpym-dis-chexo-psdab 12106bim-eta-oem-zdap12155piraz-dimephmep-mes-dfzdap 12107am2py-m24thizman2-meo-12156piraz-ams2-imo-betapy

betainyl121572py-edian2-ocho-psdab 12108dhim-trias-5pho-betainyl12158piraz-diaz-cpro-asppha 12109bim-amn2-oem-bnsdap12159mam2py-dis-fo-bsdap 12110pippy-pipa-imo-dfzdap121604pmhs-m24thizman2-aco-psdab 12111chhs-dimen-fo-betapy12161hythpym-ams3-emo-bsdap 121122py-mepipe-no2-bhsdap12162morhs-24thizman2-emo-bsdap 12113ppy-m24thizman2-chexo-12163im-pyma2-ocho-bnsdap

glyzdap12164mepip-tetradi-emo-dfzdap 12114piraz-n24thiman-5amo-dfzdap12165piraz-tetradi-napo-aspibua 12115morhs-din-men-zdap12166dmthpym-mepipen2-meo-glyzdap 12116mam2py-amn3-peo-psdab12167am2py-dimephmep-cnmo-zdap 12117bim-tetradi-5amo-bhsdap12168bim-dimephmep-eoco-mezphe 12118mam2py-pymea-fo-zorn12169prhs-din-mmen-psdab 121192py-pyma2-eoco-betapy12170thpym-dimephmep-5amo-bhsdab 12120amim-ams2-chexo-psdab12171dhim-dis-no1-bphabs 121214pmhs-amn2-no1-betainyl12172pyr-24thiz-oem-bphabs 12122amthiaz-diphmep-mommo-psdap12173bim-din-pro-bphabs 12123bim-eta-mes-zdap12174imhs-hexadi-meteto-asppha 12124deam-m25thiz-fo-betainyl12175deam-amn3-eoco-aspibua 12125bhs-din-eoco-bphabs12176mam2py-tetradi-napo-bhsdap 121264pmhs-amn3-ocho-bphabs12177hythpym-ams2-meo-tsdap 12127dhim-pipa-napo-zdab121782py-pazin-hso-betainyl 12128dhim-dimephmep-chexo-12179amim-25oxman2-meto-bphabs

betainyl12180phhs-am2-sem-nzdap 12129pyraz-mepipe-mmen-betapy12181piraz-dimephmep-4pho-oxal 12130me-edian2-oem-aspibua12182bim-eta-meo-psdab 12131am2py-m25thiz-cpro-ppsdap12183bhs-24thizman2-napo-bphabs 12132bz-pentadi-oem-glyzdap12184thpym-pazin-no1-bnsdap 12133bim-mepipen2-paco-ibsdap12185nim-pipa-cpro-aspibua 12134imhs-tridi-mmen-betainyl12186amim-dimen-eoco-betainyl 12135prhs-25oxman2-imo-bhsdab121872py-amn3-meo-zdap 12136pippy-mepazin-oem-oxal12188me-trias-meo-zdab 12137thpym-m25thizman2-aco-zdabs12189am2py-dimen-no2-dfzdap 12138pippy-mepazin-cnmo-asppha12190piraz-dimephmem-ocho-tsdap 12139mam2py-ams3-ocho-dfzdap12191thpym-mepipe-no2-psdap 12140imhs-amo2-oem-bphabs12192me2py-pipa-no1-bsdap 12141piraz-eta2s-oeto-betapy12193thpym-ams3-baeo-psdap 12142piraz-dimen-imo-bsdap12194emnim-edia2-oem-nzdab 12143bimhs-amo2-pyo-zdabs12195bimhs-trias-meo-zdabs 12144deam-dimen-no1-thizzdap12196piraz-din-chexo-betainyl 12145am-m24thizman2-imo-aspbzla12197bimhs-thizn-no2-ppsdap 12198menim-pnymea-mes-zdabs12248bimhs-diphmem-men-bhsdap 12199imhs-pipmea-meo-asppha12249ec-mea2s-5pho-bhsdap 12200bhs-eta-oem-zdab12250bim-24thizman2-5pho-psdap 12201fthpym-mepipe-5pho-zdab122512py-mepipe-oem-bnsdap 12202bimhs-24thiman2-fo-aspibua12252morhs-diphmem-napo-bhsdap 12203bim-amn3-5amo-glyzdap12253pippy-diaz-cnmo-bsdap 12204chhs-pipa-meo-psdap12254dpam-amo2-napo-betadcph 12205impy-24thizman2-men-psdap12255thpym-dipch-eoco-dfzdap 12206npip-trias-mes-zdab12256impy-amn2-ocho-bsdap 12207edothpym-m24thizman2-chexo-12257bim-pnymea-5pho-ppsdap

betadcph12258hythpym-amo2-5amo-aval 12208me2py-dimephmep-meo-zorn12259z-pymea-5pho-asppha 12209im-mepipe2-oem-npsdap12260imhs-mepipen2-5amo-bphabs 12210dhim-am2-oem-nzdab12261hythpym-mepipe-meteto-tsdap 12211fthpym-pipmes-no1-betadcph12262z-m24thizman2-no2-aspbzla 12212bimhs-24thiz-peo-mezphe12263am2py-dimephmep-imo-zdab 12213pippy-hexadi-mes-betainyl12264imhs-am3-sem-nbetameph 12214thpym-m24thizman2-pyo-asppha12265am2py-mepazin-meo-aspbzla 122152py-amn2-5pho-bnsdap122662py-amn2-oem-betapy 12216thpym-pnymea-meo-glyzdap12267thpym-mepipe-eoco-betapy 12217n2py-24thizman2-5amo-ppsdap12268bim-trias-no1-zdabs 12218piraz-diphmep-mes-psdap12269impy-mepipe-fo-betadcph 12219dpam-pazin-5amo-bhsdab12270bhs-pazin-no1-zdap 12220piraz-diphmep-meo-zdap12271impy-25oxman2-napo-bhsdab 12221pippy-25thiz-oem-tsdap12272bim-din-hso-psdab 12222amim-mepipe-oem-csdap12273mam2py-mepipe2-oem-nbeta34- 12223nmhs-pipa-no1-bhsdapdimeoph 12224pippy-m25thiz-daco-zdabs12274imhs-mepipe-no1-psdap 12225am2py-ams3-cpeo-glubzla12275me2py-amn3-mes-zdapee 12226hythpym-dis-chexo-zdap12276bim-pazin-eoco-bsdap 12227bhs-edian2-no1-bsdap12277bimhs-thizn-men-aspibua 12228ec-mepazin-fo-bhsdab12278bhs-diphmem-eoco-betainyl 12229amim-dimephmep-fo-psdap12279pyr-pipmes-fo-aspibua 12230dpam-amo2-meo-zdab12280nmor-thizn-emo-zdap 12231am2py-pnymea-napo-glyzdap12281me-diphmep-eoco-zdab 12232mam2py-din-5amo-bphabs12282bz-trias-napo-aspibua 12233z-tridi-mommo-dfzdap12283npip-thizn-meteto-asppha 12234imhs-m24oxman2-cpro-ppsdap12284bhs-thizn-fo-glyzdap 12235hythpym-24thizman2-4pho-12285pyraz-pymea-oem-betapy

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asppha12571prhs-25oxman2-mes-bhsdap 12522bhs-mepipe-ocho-bnsdap12572me2py-pymea-5amo-betadcph 12523bhs-eta-no1-zdabs12573mam2py-din-imo-bsdap 12524bimhs-mepipe2-oem-nbetameph12574dhim-24thiz-emo-bphabs 12525im-pipmea-cpro-aspbzla12575thpym-eta-eoco-dfzdap 12526bhs-eta-napo-bhsdap12576am2py-25thiman2-fo-aspibua 125272pmhs-amo2-mes-bphabs12577impy-pipmea-no2-bhsdap 12528am4py-pyma2-cpro-bnsdap12578am4py-m25thizman2-meto- 12529hythpym-din-napo-zdabsbphabs 12530dhim-am3-oem-nbetameph12579bim-mepipe2-oem-nzdab 12531me2py-3diaz-fo-betadcph12580piraz-dimen-oem-betaet 125322pmhs-tetras-imo-thizzdap12581morhs-mea2s-imo-glubzla 12533bim-m24thizman2-emo-glupha12582thpym-thizn-chexo-zdab 12534pippy-props-no1-mezphe125832py-am3diaz-napo-zdab 12535bhs-pipa-eoco-oxal12584z-amn2-meo-bnsdap 12536mam2py-dimen-no2-glubzla12585pyrhs-trias-5amo-betadcph 12537hythpym-pipa-no2-bsdap12586cl3pyme-24thiz-meo-mezphe 12538impy-pymea-napo-betadcph12587thpym-am3-sem-nbetapy 125394pmhs-mepipe2-oem-nzdap12588pyr-mepazin-no1-glyzdap 125402py-mepipen2-mes-bphabs12589z-dis-hso-bsdap 12541bhs-dimephmem-oem-zdapee12590thpym-dimephmep-mes-bhsdab 12542bhs-edian2-no2-zdap12591bimhs-amo2-chexo-bhsdap 125432py-amo2-men-bnsdap12592impy-25oxman2-ocho-asppha 12544nmhs-butn-no1-ibsdap12593dhim-pazin-fo-osdap 12545pippy-n24thiman-emo-glupha12594thpym-mepipe-oem-bnsdap 12546bim-3diaz-imo-betapy12595dmbim-pipmea-hso-zdap 12547n2py-mepipen2-no2-bphabs12596mam2py-mea-5pho-betainyl 12548impy-amn2-meo-psdab12597impy-mepipe-eoco-betapy 12549morhs-pnymea-pheo-bhsdab12598am4py-mepipe-eoco-oxal 12550imhs-edian2-no1-bhsdap125992py-pazin-ocho-psdap 12551phpip-m24thizman2-eoco-12600hythpym-amo3-imo-asppha

glupha126012py-pipmea-ocho-aspibua 12552piraz-n2nme2n-5pho-zdabs12602amim-dio-meo-dfzdap 12603prhs-mepipen2-no1-betapy12654nim-24thizman2-mmen-aspbzla 126042py-trias-imo-glyzdap12655nmor-dimephmem-oem-aspbzla 12605bim-3pazin-meo-bhsdab12656mam2py-24thiz-paco-psdap 126062py-props-meo-psdap12657bim-25thiman2-ocho-bhsdap 12607pippy-dimephmep-eoco-dfzdap12658cl3pyme-mea2s-ocho-psdab 12608am2py-pymea-oem-glyzdap12659gua-25thiman2-imo-zdap 12609fthpym-25oxman2-no1-csdap12660bimhs-butn-daco-dfzdap 12610mam2py-m25thiz-fo-zdap12661impy-pymea-imo-aspbzla 12611im-pentas-no1-zdabs12662piraz-tetradi-imo-glyzdap 12612mam2py-diphmep-5pho-ppsdap12663thpym-din-meteto-bsdap 12613phpip-n2o2n-imo-dfzdap12664imhs-pnymea-imo-glubzla 12614am-mepipe-imo-bsdap12665bim-mepipe-mes-bsdap 12615imhs-tridi-napo-aspbzla12666mepip-mepazin-mes-asppha 12616dhim-am3-sem-nbetabnaphth12667me-indan2-meo-zdabs 12617pyraz-am3-oem-npsdap12668me2py-dimephmem-meo-mezphe 12618hythpym-ams2-chexo-bnsdap12669prhs-24thiman2-mes-psdab 12619thpym-amn2-5pho-aspbzla12670bhs-dimephmem-pro-betapy 12620imhs-dimephmep-no1-betainyl12671bzl-m24thizman2-5amo-aspbzla 12621morhs-props-4pho-glyzdap126722py-amo2-5pho-betadcph 12622impy-m25oxman2-5amo-bhsdab12673dmam-diphmem-no1-asppha 12623me2py-dimephmep-men-zdab12674me2py-m25thiz-cno-asppha 12624bz-mepipe2-oem-nzdab12675impy-dimen-imo-bphabs 12625dmbim-dimen-oem-psdapee12676hythpym-24thiman-mes-zdap 12626gua-m24thiz-mmen-bnsdap12677mam2py-m24thizman2-meo-bsdap 12627mam2py-hexas-ocho-bhsdab12678am4py-amo2-meo-aspaba 12628imhs-edian2-meo-betapy12679thpym-m25thiz-meo-betapy 12629hythpym-din-ocho-betainyl12680impy-din-fo-psdab 12630mam2py-propn-men-bhsdap12681pippy-am2-oem-nbetapy 12631thpym-25thiz-4pho-tsdap12682chmhs-props-fo-psdab 12632chmhs-ams3-napo-bphabs12683me2py-pyma2-ocho-ppsdap 12633pippy-m25thiz-imo-betadcph12684bhs-tetradi-napo-thizzdap 12634tolhs-pipmea-fo-psdap12685dhim-tridi-eoco-psdab 12635bimhs-diphmep-5amo-betadcph12686hythpym-ams2-mes-betainyl 12636z-amn3-eoco-dfzdap12687thpym-24thizman2-peo-dfzdap 12637bhs-pymea-daco-aspibua12688am-amn2-imo-betapy 12638dhim-dimephmem-mommo-zlys12689pippy-din-no2-aspaba 12639mam2py-24thiman2-emo-bphabs12690am2py-diphmem-5amo-zlys 12640thpym-pazin-oem-zdap126912py-2pazin-pyo-betainyl 126412py-pnymea-eoco-bhsdab12692ppy-edian2-oem-glyzdap 12642imhs-mepazin-mes-dfzdap12693mam2py-m24thizman2-oem- 12643bim-amn3-5pho-betainylglyzdap 12644ppy-amn3-5pho-zdab12694amim-25thizman2-aco-zlys 12645dhim-am2-oem-npsdap12695impy-tetradi-meo-asppha 12646thpym-edia2-oem-nzdap12696menim-pentas-fo-zorn 12647pippy-am2-oem-npsdap12697impy-edian2-meto-zdabs 126482pmhs-din-aco-psdapee126982py-m24thizman2-chexo- 12649dmbim-m24thiman2-mommo-aspbzla

bhsdab12699n2py-pipmes-eoco-csdap 126502pmhs-thizn-napo-zdab12700piraz-dimephmem-ocho-bsdap 12651bhs-24thizman2-men-psdapee12701piraz-pipmea-pro-betadcph 12652am2py-dimephmem-emo-zdabs12702am2py-mepipe2-oem-npsdap 12653deam-diphmep-napo-zdap12703am2py-edian2-chexo-psdap 12704me2py-pipmes-oem-betapy12753ec-diphmem-napo-zdabs 12705mam2py-am3-oem-nbeta34-12754hythpym-tridi-oem-zdap

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meo-csdap12780prhs-trias-oeto-bsdap 12730me2py-am2-oem-nzdab12781bim-am2-sem-nbeta34dimeoph 12731bimhs-pyma2-cno-aspibua12782pippy-mepipe-cpro-aspbzla 12732gua-dimephmem-napo-psdab12783am2py-trias-daco-psdab 12733deam-mepipen2-5pho-bhsdab12784hythpym-hexas-5pho-zdabs 12734imhs-eta-no2-psdap12785hythpym-pymea-baeo-ppsdap 12735me-ams2-no2-dfzdap12786morhs-thizn-no2-glyzdap 127362py-edian2-meo-bsdap12787bimhs-dipch-aco-tsdap 12737am2py-dis-men-psdapee12788bim-diphmep-no2-bhsdab 12738am2py-dis-chexo-zdapee12789imhs-eta-eoco-zdap 12739pippy-mepazin-ocho-bhsdap12790hythpym-m25thizman2-5pho- 12740pyrhs-din-ocho-bsdapbetainyl 12741thpym-24thizman2-no1-12791pippy-mepipen2-fo-psdab

betainyl12792bim-amo2-eoco-dfzdap 12742nim-pazin-5amo-aspibua12793am2py-pipa-mmen-aspibua 12743am-mepipe2-sem-nbetabnaphth127942py-m25thiz-eoco-mezphe 12744am2py-pipa-men-asppha12795thpym-dimephmep-no1-betainyl 12745am2py-dimephmep-imo-zdap12796imhs-pipa-ocho-psdab 12746tolhs-mepipen2-chexo-glyzdap12797am2py-amo3-chexo-zdab 12747pyraz-diphmem-chexo-zdabs12798mepip-m24thizman2-pro-csdap 12748bim-amn2-meo-psdab12799amim-m25thizman2-mmen-zlys 12749menim-dimephmep-5pho-osdap12800dhim-edian2-mommo-bhsdab 12750edothpym-pipmea-meo-zdabs12801bim-24thiz-oem-bnsdap 12751ppy-mepipen2-oem-bhsdab12802impy-m24thizman2-napo- 12752amim-m25thizman2-ocho-zdabthizzdap 12803mam2py-m24thizman2-12853me2py-m24thizman2-emo-asppha

men-ppsdap12854dhim-m24thiman2-meo-betadcph 12804pippy-din-fo-psdap12855bim-edian2-napo-betapy 12805am4py-m25thizman2-chexo-12856bhs-edian2-4pho-bphabs

mezphe12857dmbim-amo2-no2-betapy 12806phpip-pnymea-men-asppha12858bimhs-24thizman2-imo-glyzdap 12807me-dimephmep-imo-psdab12859piraz-pipa-eoco-bhsdap 12808nmhs-m24thiman2-fo-zdabs12860thpym-mepazin-men-bnsdap 12809emnim-dimephmep-eoco-aspibua12861edothpym-pipa-mecpo-dfzdap 12810bim-eta-ocho-bhsdap128622pmhs-pentadi-eoco-bphabs 12811menim-diphmep-baeo-zdab12863dhim-din-no1-psdab 12812impy-m25thiz-mes-csdap12864bimhs-edian2-oeto-bhsdab 12813pippy-dimephmep-napo-bhsdap12865pyrhs-pnymea-mes-dfzdap 12814edothpym-m25thiz-cno-bsdap12866bhs-mepipe-meo-zdap 12815mam2py-edian2-cnmo-betainyl128672py-2pazin-baeo-glyzdap 128164pmhs-pipmeo-no1-aspbzla12868bhs-diphmep-imo-zdab 12817am2py-24thizman2-eoco-csdap12869mam2py-props-men-betainyl 12818impy-thizn-chexo-psdap12870hythpym-eta-eoco-thizzdap 12819ec-tetradi-nmo-bhsdab12871pyrhs-mepipe-baeo-zdab 12820morhs-amn3-mmen-bhsdab12872bhs-eta-meo-bhsdap 12821hythpym-amo2-imo-psdab12873hythpym-ams2-paco-glyzdap 12822me2py-m25thiz-5pho-zorn12874imhs-mepipe-ocho-zdab 12823mepip-amo2-oem-bphabs12875am2py-butn-5amo-bsdap 12824mam2py-propa2s-fo-glupha12876nmor-mepipe2-oem-npsdap 12825tolhs-24thizman2-hso-bhsdab128772py-pazin-eoco-zdab 12826mam2py-amn2-eoco-dfzdap12878am2py-edian2-oem-mezphe 12827imhs-pymea-oem-csdap12879mam2py-25thiz-5pho-mezphe 12828thpym-eta-no1-bnsdap12880impy-indan2-no1-psdap 12829pyr-thizn-chexo-aspibua12881thpym-pazin-no1-zdab 12830imhs-mepipe-ocho-betapy12882bimhs-amo2-napo-bnsdap 12831bhs-dimen-5amo-bnsdap12883impy-am3-oem-nbetapy 12832chmhs-amn3-eoco-aspbzla12884me2py-24oxman2-oem-mezphe 12833piraz-m25thiz-mes-dfzdap12885amthiaz-dimephmem-fo-betapy 12834amim-m24thizman2-oem-aspibua12886bim-mepipe-5pho-bhsdap 128352py-tetradi-napo-ppsdap128872pm%s-24thiz-men-bhsdap 12836dhim-m24oxman2-men-bnsdap12888am4py-dipch-imo-ibsdap 128372py-pazin-mes-bsdap12889me2py-din-oem-bnsdap 12838chmhs-dimen-mes-dfzdap128902py-25thiman2-cno-bhsdab 12839npip-amo2-oeto-zdabs12891imhs-eta-5pho-bhsdap 12840hythpym-mepazin-napo-dfzdap12892dhim-am3diaz-mes-zlys 12841bhs-m25thiz-pheo-aspibua12893mam2py-amn2-men-zdap 12842me2py-24thizman2-5pho-dfzdap12894z-m25oxman2-imo-bnsdap 12843hythpym-dimen-5amo-bnsdap12895dhim-mepipen2-chexo-bphabs 12844phpip-dimephmep-mes-osdap12896dpam-mepazin-ocho-zdab 12845bim-eta-no1-psdap128972py-mepipe-no2-psdap 12846bimhs-mepipen2-5pho-ppsdap12898phhs-m25thiz-no2-zdabs 12847mam2py-dimephmem-men-zdap12899am4py-pipmea-men-ibsdap 12848bimhs-ams2-paco-betainyl12900tolhs-pnymea-oem-asppha 12849bim-mepipe-oem-psdab12901bim-pazin-meteto-csdap 12850imhs-amn3-eoco-zdap129024pmhs-mepazin-5pho-aspibua 12851piraz-mepipe-napo-bhsdab12903tolhs-mepipe-meo-betadcph 12852hythpym-pipmes-imo-zdabs12904dpam-pymea-paco-betainyl 12905amim-n2nme2n-4amo-psdap12956mepip-eta-chexo-zdab 12906bim-eta-meto-aspibua129574pmhs-pyma2-5pho-betadcph 12907bhs-pazin-5pho-psdap12958piraz-diphmem-oem-asppha 12908amthiaz-edia2-oem-nzdab12959dhim-am3diaz-meo-zdab 12909thpym-eta-cnmo-bsdap12960bimhs-pyma2-cnmo-bsdap 12910bhs-amn3-paco-psdab12961imhs-mepipen2-ocho-betapy 12911me2py-m24thiz-oeto-glyzdap12962bzl-pazin-5amo-tsdap 12912hythpym-m24thizman2-mes-129632py-amn2-oem-psdap

bnsdap12964dhim-am2-sem-npsdap 12913hythpym-pazin-oeto-betainyl12965bhs-dimephmem-imo-csdap 12914thpym-amn2-no2-zdab12966pippy-pyma2-men-aspbzla 12915thpym-eta-eoco-bnsdap12967nim-mepipe-5pho-zdab 12916imhs-pipmea-men-csdap12968amthiaz-thizn-emo-thizzdap 12917hythpym-diphmep-men-aspibua12969impy-m24thizman2-aco- 12918bim-edian2-5pho-bsdapbetadcph 12919moegua-thizn-meo-zdap12970mam2py-m25thiz-eoco-csdap 12920pippy-amo2-5pho-bhsdap12971me2py-thizn-chexo-betainyl 12921pippy-24thizman2-oem-bphabs12972imhs-pyma2-cpeo-glyzdap 12922hythpym-pymea-imo-mezphe12973dmam-tridi-chexo-psdab 12923hythpym-mepazin-no1-betapy12974nmor-ams2-napo-zdap 12924am2py-props-cnmo-betapy12975hythpym-din-no2-psdap 12925me2py-m24thiman2-fo-ibsdap12976piraz-tridi-fo-bhsdab 12926piraz-am3diaz-napo-aspbzla12977am2py-25thiman2-imo-oxal 12927mam2py-mepipen2-oem-psdab12978chhs-eta-cpro-mezphe 12928me-tridi-no2-zdab12979mam2py-ams2-no2-betainyl 12929dmbim-diphmem-eoco-zdabs12980pippy-24thiz-chexo-zlys 12930piraz-ams2-men-mezphe12981n2py-24thiz-men-bhsdap 12931amim-dis-mes-betadcph12982npip-m25thiz-oem-betadcph 12932piraz-pnymea-mmen-bhsdap12983dhim-edian2-no2-bhsdab 12933bim-25oxman2-cpeo-bphabs12984edothpym-m25thiz-oem-aspbzla 12934z-24thizman2-no2-betapy12985me2py-mea2s-imo-bsdap 12935bimhs-am3diaz-5amo-zdabs12986ppy-mepipen2-no1-betainyl 12936imhs-amn2-eoco-psdap12987bim-amn2-oem-psdab 12937me2py-hexadi-emo-bnsdap12988mepip-ams3-no1-betainyl 12938mam2py-amn3-5amo-bnsdap12989imhs-eta-oem-psdap 12939emnim-mepazin-mes-betadcph12990bim-eta-oem-psdap 12940bimhs-diphmep-napo-bphabs12991piraz-dimephmem-meo-asppha 12941am-n2nme2n-mecpo-bsdap12992piraz-eta-5pho-zdabs 12942pippy-am3-oem-nbetapy12993bhs-eta-5pho-bnsdap 12943mam2py-amn2-mes-zdab12994me-edian2-5amo-glubzla 12944bim-am3-sem-nbetameph12995hythpym-trias-cno-aspbzla 12945piraz-diphmep-5pho-psdapee12996am2py-mepipen2-no2-betaet 12946impy-edian2-oeto-psdap12997pyr-24thiz-imo-glyzdap 12947me-pnymea-5amo-bhsdap12998imhs-amn2-mes-betapy 12948bim-edian2-no2-betapy12999dhim-pentadi-fo-csdap 12949bhs-trias-oem-zdap13000me-edian2-chexo-betadcph 12950bhs-amn2-mes-bhsdap13001bhs-n24thiman-mes-zdabs 12951bimhs-trias-no2-asppha13002bimhs-dis-emo-dfzdap 129522py-tridi-hso-glupha13003mepip-m25thizman2-no2-mezphe 12953n2py-24thiz-pheo-oxal13004hythpym-tridi-no2-betainyl 12954gua-dimen-mommo-asppha13005piraz-thizn-no1-bsdap 12955impy-pnymea-pheo-csdap13006npip-dimephmem-ocho-zdap 13007bim-din-eoco-bsdap13058amim-ams2-men-dfzdap 13008amim-m25thiz-hso-betadcph13059tolhs-pnymea-no1-aspibua 13009dpam-pyma2-men-psdap13060dmthpym-pymea-emo-zdapee 13010mam2py-25thizman2-men-zorn13061bim-edian2-eoco-betapy 13011bim-pipa-chexo-betadcph13062hythpym-amn2-mmen-zdap 13012bim-eta-5pho-bsdap13063bim-24thiz-cpeo-psdab 130132py-m24thiman2-imo-bhsdab13064menim-amn2-men-mezphe 13014imhs-mepazin-pheo-zdab13065bim-mepazin-5amo-ppsdap 13015imhs-pazin-no1-bhsdap13066me-pipa-4amo-psdap 13016bimhs-amo2-imo-aspaba13067bimhs-edian2-no1-aspibua 13017hythpym-dio-emo-csdap13068pippy-tetradi-oem-aspbzla 13018amim-dimen-chexo-csdap13069bhs-propa2s-5amo-zdabs 13019bim-m25thiz-emo-dfzdap13070bim-pnymea-napo-zlys 13020pippy-am2-oem-nzdab13071pippy-pipa-napo-zdap 13021dhim-pipmea-5pho-glyzdap13072dhim-edian2-meteto-ppsdap 13022ppy-eta2s-5pho-bhsdab13073bhs-pazin-no2-zdab 13023dhim-24thizman2-nmo-bhsdab13074am2py-thizo-emo-zdabs 13024dmam-dimen-fo-glubzla13075bim-edian2-oem-bhsdap 13025amthiaz-amo2-ocho-bphabs13076ibhs-24oxman2-imo-bnsdap 13026tolhs-tetradi-meto-thizzdap13077hythpym-thizo-pro-asppha 13027dhim-edian2-men-zdab13078pippy-pipa-meto-bhsdab 13028dhim-amo3-oem-glyzdap13079bhs-indan2-5amo-glubzla 13029pyr-butn-oem-zdab13080pippy-pymea-5pho-dfzdap 13030amim-mepipen2-pheo-bnsdap13081cl3pyme-pnymea-men-zdap 13031thpym-pipmea-no2-mezphe13082impy-dis-mes-bnsdap 130322py-trias-emo-csdap13083thpym-eta-napo-glyzdap 13033chmhs-pazin-no2-psdap13084bim-butn-fo-psdap 13034amim-25thizman2-cpeo-glyzdap13085bimhs-ams2-no2-mezphe 13035n2py-tetradi-no1-bnsdap13086am2py-mepipe-ocho-zdabs 13036hythpym-ms-5pho-glupha13087me2py-tetradi-5amo-zdab 13037imhs-amn2-no2-bhsdap13088am4py-eta-5amo-dfzdap 13038imhs-diphmem-mmen-glyzdap13089hythpym-25oxman2-hso-zlys 13039amim-m24thizman2-ocho-bhsdap13090gua-pnymea-hso-aspbzla 13040dhim-mepipe-5amo-aspaba13091dhim-eta-paco-psdab 13041menim-ams2-cpeo-aval13092emnim-pymea-napo-bphabs 13042pippy-butn-daco-bsdap130932pmhs-mepipen2-eoco-glupha 13043am2py-dis-imo-aspbzla13094cl3pyme-pazi2n-chexo-zdap 13044dhim-25thizman2-5amo-glyzdap13095amthiaz-am3-oem-nzdap 13045mam2py-eta-imo-zdap13096thpym-amn2-eoco-zdap 13046impy-amn3-emo-zdabs13097bhs-n2nme2n-5amo-zdapee 13047bhs-dis-mmen-betadcph130982py-mepipen2-napo-aspibua 13048bhs-pipmes-napo-glyzdap13099mam2py-pipa-cnmo-aspbzla 13049dmthpym-tetradi-pheo-csdap13100imhs-tetradi-chexo-mezphe 13050me2py-m24thiz-emo-bhsdab13101hythpym-amo2-no2-zdabs 13051bhs-amn2-no1-bnsdap13102bhs-amn2-5pho-betapy 13052imhs-m25thizman2-chexo-13103am2py-trias-aco-psdapee

bphabs13104dhim-3pazin-nmo-bnsdap 13053bimhs-amn2-fo-bhsdap13105bim-edian2-no1-psdab 13054imhs-dimen-emo-glyzdap13106am2py-pazi2n-ocho-glyzdap 13055bimhs-eta-oem-bhsdap13107dhim-pipmea-oem-zorn 13056chhs-25thiman2-fo-mezphe13108gua-din-meto-aspibua 13057bimhs-3diaz-hapo-zdap13109bimhs-pentadi-5amo-bnsdap 13110mepip-pymea-imo-asppha13161bimhs-indan2-meo-zdap 13111dpam-m25thiz-napo-bsdap13162thpym-eta-5pho-bsdap 13112imhs-diphmem-napo-thizzdap13163bimhs-mepipen2-5amo-aspbzla 13113imhs-m24thizman2-mes-psdab13164z-m25thiz-cnmo-thizzdap 13114thpym-25oxman2-fo-bsdap131652py-24thiz-meo-asppha 13115bimhs-thizn-meteto-glyzdap13166thpym-edia2-sem-nbetameph 13116z-tetradi-chexo-csdap13167bim-mepipe-eoco-psdap 13117mam2py-24oxman2-no2-bphabs13168amim-butn-no1-aspibua 13118am2py-pymea-mes-dfzdap13169mam2py-m24thizman2-mecpo- 131192py-amn3-napo-zdapglyzdap 13120bhs-amn2-meo-psdap13170bim-dis-nmo-bhsdap 13121am2py-tetras-meo-psdap13171mam2py-amo3-chexo-csdap 13122amthiaz-24thiz-mes-aspbzla13172hythpym-amn3-chexo-glupha 13123bhs-n2nme2n-no1-aspbzla13173fthpym-25thiman2-men- 13124im-diphmem-meo-betaetbetadcph 13125imhs-tridi-oem-ppsdap13174bim-diphmep-no2-zdap 13126imhs-pazin-daco-bsdap13175pippy-amo2-4amo-glyzdap 13127bhs-eta-no1-bsdap13176hythpym-pazi2n-no2-betapy 13128pyraz-pazin-emo-betainyl13177dhim-trias-imo-dfzdap 13129thpym-din-mommo-mezphe13178bimhs-thizn-5pho-betapy 13130ibhs-thizn-chexo-bsdap13179me2py-pazin-mecpo-bhsdab 13131menim-dis-oem-zdap13180npip-pnymea-mes-asppha 13132bhs-amn2-no2-bnsdap13181dhim-pnymea-fo-dfzdap 13133bim-amn2-mecpo-dfzdap13182amim-pipmea-4pho-bhsdap 13134phpip-dis-5amo-zdap13183bzl-24thizman2-imo-bnsdap 13135hythpym-dimephmem-oem-13184im-m25thiz-imo-bhsdap

aspibua13185amim-25thizman2-emo-osdap 13136imhs-pazin-cno-csdap13186pippy-pazi2n-fo-psdapee 13137hythpym-diphmem-oem-bphabs13187ppy-mepipe-mommo-psdab 13138amim-trias-peo-psdab13188bhs-m24thizman2-no2-mezphe 13139z-hexas-cpeo-zdap131892py-dich-5pho-glyzdap 13140dhim-amn2-no2-zdab13190mam2py-pipa-meo-betainyl 13141am2py-25oxman2-4pho-psdapee13191im-am3-oem-nbetapy 13142am2py-amo2-pheo-bsdap13192menim-pymea-meo-betadcph 13143bhs-thizn-meteto-psdap13193impy-24thiz-cnmo-psdab 13144bim-pymea-ocho-zdabs13194bhs-25oxman2-cno-glyzdap 13145bimhs-diphmep-men-glubzla13195me2py-pymea-daco-zlys 13146me2py-amo2-chexo-zdapee13196bhs-pazin-oem-zdab 13147mam2py-mepazin-chexo-bphabs13197nim-mepazin-men-glyzdap 13148pippy-amn2-no2-zdabs13198thpym-ams2-chexo-betainyl 13149bhs-edian2-no2-psdap13199amthiaz-propn-men-zdab 13150dmthpym-3diaz-men-betadcph13200impy-amo3-mes-bphabs 131512pmhs-amo3-paco-mezphe132012py-m25oxman2-mmen-zdapee 13152me2py-amn3-napo-betadcph13202thpym-dimephmep-imo-zdap 13153dmbim-pipmea-meo-psdapee13203mam2py-am3diaz-chexo-zdap 13154moegua-diaz-oem-osdap13204bz-butn-no1-zdap 13155phhs-ms-4amo-zdab13205bim-mepipe-no2-betapy 13156mam2py-dipch-meteto-dfzdap13206npip-edia2-oem-nbeta34- 13157ppy-am3-sem-nzdapdimeoph 13158bhs-mepazin-men-aspbzla13207thpym-edian2-oem-betapy 13159bhs-pazin-no1-betapy13208npip-mepipe-meo-asppha 13160bhs-amn3-no1-bhsdap13209imhs-pazi2n-men-zdap 13210me2py-din-mes-zdab13261am4py-m25thizman2-imo-bhsdap 13211hythpym-edian2-no2-betapy13262am2py-pipa-oeto-betainyl 13212nmhs-pazin-eoco-psdab13263pyraz-amn3-nmo-zdabs 13213bhs-dimen-eoco-psdab13264bim-edian2-5pho-betapy 13214me2py-24thiz-ocho-asppha132652py-pazin-no2-psdab 13215imhs-din-mecpo-betadcph132662py-pazin-5pho-zdap 13216amim-dimephmem-napo-psdab13267deam-24thizman2-nmo-betainyl 13217impy-m25oxman2-fo-csdap13268phhs-dimephmem-cpro-bhsdab 13218bimhs-dimephmem-5amo-bhsdap13269fthpym-din-meto-betadcph 13219hythpym-m25thiman2-no1-13270bimhs-pnymea-5amo-aspaba

dfzdap13271imhs-eta-cpro-mezphe 13220bim-24thizman2-5amo-psdab13272thpym-tridi-mes-aspbzla 13221bhs-pazin-5pho-zdab132732pmhs-mepipe-5pho-betaet 13222dpam-dimephmem-5pho-bhsdab13274bhs-amn2-mes-bsdap 13223imhs-pazin-mes-betapy13275thpym-25thiman2-no2-dfzdap 132242py-pazin-5amo-csdap13276pippy-pymea-no2-zdapee 13225im-dimephmep-5amo-ppsdap13277me2py-thizn-emo-bhsdap 13226impy-thizn-5pho-aspbzla13278cl3pyme-dimephmep-emo-psdab 13227imhs-din-oem-oxal13279piraz-thizn-5pho-betadcph 13228pippy-diphmem-chexo-zdap13280mam2py-amo2-paco-psdapee 13229bim-am3diaz-5amo-bnsdap13281dhim-amn2-imo-tsdap 132302py-3diaz-ocho-mezphe13282me2py-25oxman2-hso-bsdap 13231dhim-dipch-cno-mezphe13283emnim-thizn-meo-zdapee 13232thpym-2pazin-mmen-ibsdap13284am2py-dio-cnmo-bhsdab 13233amim-diphmep-5pho-bhsdab13285thpym-pazin-no1-bhsdap 13234dhim-dimen-daco-bhsdab13286thpym-trias-eoco-betapy 13235ppy-diphmem-meo-bphabs13287pippy-pnymea-cnmo-betapy 13236dhim-thizo-fo-bnsdap132882py-dis-emo-zdapee 13237bimhs-dimephmep-oeto-zdap13289phhs-n2o2n-meo-aspbzla 13238bim-mepipe-baeo-psdap132904pmhs-m25thiz-chexo-zorn 13239mam2py-amn3-fo-glyzdap13291pyrhs-eta-no1-zdab 132402py-25thiman2-eoco-dfzdap13292deam-dis-chexo-bhsdab 13241bimhs-pazin-fo-zdab13293me-edian2-no2-bnsdap 13242mam2py-pyma2-fo-psdab13294pippy-pipmea-fo-aspibua 13243amim-25oxman2-cno-zdap13295bhs-pipmea-fo-aspaba 13244impy-pazin-eoco-aspbzla13296fthpym-pipmeo-eoco-psdap 13245me2py-mepazin-oem-asppha13297chmhs-diphmem-chexo-csdap 13246nmhs-mepipe-peo-aspbzla13298imhs-eta-oem-psdab 13247hythpym-mepazin-cpeo-aspaba13299am4py-pazin-men-zdab 13248thpym-24thiman-5pho-bhsdap13300piraz-m24thizman2-5amo-psdap 13249am-25oxman2-ocho-asppha133012pmhs-dimen-oeto-betapy 13250nmhs-ams3-cpeo-psdab13302menim-dimen-chexo-psdapee 13251hythpym-dimephmem-hso-bphabs13303thpym-mepazin-5pho-psdab 13252nmor-m25oxman2-cpro-bphabs13304menim-edian2-peo-ppsdap 13253bhs-pyma2-ocho-oxal13305impy-edia2-oem-zdab 13254piraz-mepipen2-men-mezphe13306chmhs-diphmep-no2-mezphe 132552py-dimephmep-4pho-aspbzla13307me-m25thiz-5pho-betadcph 13256phhs-amn2-men-aspbzla13308bhs-am2-sem-nbeta34dimeoph 13257bhs-tridi-mes-bnsdap13309bzl-mepipe2-oem-nzdab 13258ec-tridi-mes-glubzla13310nim-m25thizman2-men-osdap 13259am2py-dipch-paco-betadcph13311dhim-mepipe-oem-zdabs 13260cl3pyme-m25thiz-pheo-bsdap13312mam2py-amo2-men-psdap 13313impy-pnymea-mommo-aspbzla13364bhs-amn3-5pho-zdap 13314amim-24oxman2-no2-betapy13365dhim-eta-men-bsdap 13315npip-dis-oem-zdap13366pippy-dimephmem-baeo-zdap 13316pippy-diphmep-napo-bsdap13367imhs-dimen-emo-glyzdap 13317moegua-m25thiz-ocho-betadcph13368amim-ams3-fo-glupha 13318pyrhs-propa2s-mes-csdap13369edothpym-pnymea-mes-betainyl 13319bhs-m25thiz-chexo-aspibua13370mam2py-n24thiman-no2-betaet 13320thpym-25oxman2-meteto-zdap13371hythpym-pipa-mmen-bnsdap 13321bhs-edian2-meo-bhsdap13372bim-din-imo-zdap 13322bim-3pazin-mecpo-oxal13373bhs-thizn-no2-bhsdab 13323mam2py-amn2-emo-zdab13374bimhs-amn3-imo-zdap 13324bhs-eta-no1-betapy13375dhim-pipa-fo-zlys 13325mam2py-diphmem-chexo-zdab13376am2py-pyma2-4pho-betainyl 13326pippy-25thiman2-eoco-asppha13377phpip-pipa-meo-dfzdap 13327imhs-eta-no1-betapy13378edothpym-tetradi-fo-asppha 13328thpym-ams2-4pho-zdap13379bimhs-mepazin-fo-thizzdap 13329dhim-eta-fo-psdab133802py-edia2-oem-nbetameph 13330dhim-tridi-mes-betapy13381me2py-dimephmem-imo-psdap 13331amim-dimephmep-emo-dfzdap133822py-diphmep-pyo-bhsdap 13332edothpym-pazin-mes-betaet13383amim-24thiman2-emo-psdab 13333am-25thiman2-fo-glyzdap133842pmhs-tridi-eoco-aspibua 13334hythpym-trias-5amo-glyzdap13385me2py-pyma2-eoco-csdap 13335thpym-eta-mes-betapy13386bim-edian2-meo-bnsdap 13336deam-pazin-fo-betapy133872pmhs-tridi-imo-aspbzla 13337piraz-mepipen2-4amo-dfzdap13388npip-thizn-meto-bhsdap 13338hythpym-pazi2n-pro-bhsdab13389moegua-ams2-no1-psdab 13339impy-butn-nmo-bphabs13390imhs-dimephmep-oem-aspaba 13340am2py-mepipe-imo-zorn133912py-dio-5pho-bphabs 13341thpym-eta-meo-bhsdap13392amthiaz-tridi-chexo-psdap 13342imhs-pazin-meo-psdap133932py-pnymea-meo-zdap 13343bim-m24thizman2-mecpo-bnsdap13394thpym-pazin-5pho-psdap 13344dhim-pazin-men-ibsdap133952py-mepipen2-imo-csdap 13345am2py-24thiman-chexo-zdab13396dhim-diphmem-baeo-glupha 13346me2py-din-no1-zdap13397nmhs-din-men-bsdap 13347piraz-tetradi-fo-tsdap13398amim-dimen-no1-bhsdap 13348impy-dis-5pho-aspbzla13399am2py-pnymea-mes-zdabs 13349bim-amo2-mes-csdap13400edothpym-24thiz-cpeo-bsdap 13350hythpym-pymea-chexo-asppha13401dmbim-trias-meo-betapy 13351emnim-tetras-emo-aspibua13402bhs-dimephmep-ocho-betainyl 13352mam2py-pyma2-5pho-betainyl13403pyraz-amo2-chexo-ppsdap 13353ppy-amn2-5amo-aspibua13404hythpym-dimephmep-men-zdabs 13354deam-2pazin-baeo-zdab13405am2py-mepipen2-emo-bsdap 13355thpym-mepipe2-sem-nbetab13406am4py-dis-no2-dfzdap

naphth13407impy-24thiz-no1-aspibua 13356thpym-pyma2-meo-asppha13408cl3pyme-pyma2-cpeo-ibsdap 13357mam2py-ams3-imo-psdab13409hythpym-butn-cnmo-zdab 13358am2py-diphmep-no1-aspbzla13410amim-24thizman2-chexo- 13359amim-pazin-mes-thizzdapaspbzla 13360fthpym-pipa-ocho-asppha13411imhs-tetradi-meo-psdap 13361tolhs-mepipe-no1-oxal13412pippy-dimephmep-pyo-bhsdap 13362emnim-ams2-chexo-psdab13413bimhs-pipmes-men-betadcph 133632py-amn3-no2-bhsdap13414mam2py-amn2-no2-glyzdap 134152py-mepipen2-imo-betadcph13465bim-mepipe-ocho-bnsdap 13416fthpym-25thizman2-men-bhsdab13466bhs-m25oxman2-mes-psdab 134172py-eta-mes-psdap13467pippy-hexadi-fo-osdap 13418ibhs-din-men-zdap13468dmthpym-dimephmep-nmo- 13419bim-mepazin-baeo-bhsdabglyzdap 13420imhs-m25oxman2-men-bnsdap13469bimhs-tetradi-chexo-betadcph 13421mam2py-25oxman2-pro-zdab13470hythpym-dimephmem-meto-psdab 13422bimhs-ams2-aco-aspbzla13471pippy-dis-chexo-bhsdab 134232pmhs-mepipe-eoco-psdab13472piraz-m24thizman2-mecpo- 13424me-trias-5pho-zdabasppha 13425me2py-24thizman2-no2-dfzdap134732py-pnymea-cpeo-bnsdap 13426impy-tetradi-hso-bhsdap13474imhs-mepazin-meo-zdab 13427me2py-thizn-nmo-zdap13475prhs-pnymea-mes-zdap 13428me2py-pyma2-5amo-zdab13476bhs-pazin-eoco-bnsdap 13429imhs-thizn-imo-psdab13477thpym-propa2s-oem-aspibua 13430bim-pazi2n-oem-bhsdab13478cl3pyme-diphmem-5pho-zdap 13431dhim-24thiz-meo-psdab13479amim-pipa-imo-bnsdap 13432am2py-thizo-oem-zdab13480bzl-pnymea-chexo-aspbzla 13433imhs-25oxman2-emo-psdab13481ibhs-amo2-5amo-bnsdap 13434mepip-m24thizman2-meteto-13482thpym-indan2-emo-zdabs

bphabs13483me2py-m25thiz-daco-bhsdab 13435ec-diphmep-5pho-bhsdap13484pyr-dimephmep-aco-betapy 134362py-trias-oem-mezphe134854pmhs-tetradi-mes-psdab 13437mepip-n24thiman-5pho-zdabs13486dmbim-tridi-eoco-dfzdap 13438thpym-edian2-mes-zdab13487bhs-25thiz-aco-aspbzla 13439bhs-edian2-5pho-psdab13488impy-pnymea-eoco-zdab 13440impy-indan2-oem-bhsdab13489bim-eta-eoco-bhsdap 13441bhs-mepipe-5pho-zdab13490dhim-24thiz-5pho-bhsdab 13442pyrhs-m24oxman2-no1-aspibua13491nim-am2-oem-nbetapy 134432py-diphmem-5amo-psdap13492dmbim-25thiman2-fo-dfzdap 13444mam2py-diphmem-mecpo-glyzdap13493pyrhs-pymea-cno-aspibua 13445piraz-mepazin-men-betaet13494me2py-25thiman2-fo-betapy 13446me2py-thizn-fo-thizzdap13495piraz-pipmes-5pho-aspbzla 13447amim-pyma2-imo-aspbzla13496me2py-pazin-oem-zdab 13448me-amn3-napo-ppsdap13497deam-trias-5amo-ibsdap 13449nim-ms-mes-asppha13498hythpym-24thiz-5amo-mezphe 13450me2py-mepipe2-sem-nbetab13499dhim-amo2-men-csdap

naphth13500pippy-pipa-5pho-aspbzla 13451mam2py-thizs-aco-betainyl13501mam2py-pazin-ocho-aspbzla 13452am2py-pyma2-chexo-dfzdap13502chmhs-amo3-paco-bnsdap 13453nmor-pipmea-cnmo-bnsdap13503bhs-eta-5pho-psdab 13454imhs-24thizman2-fo-zdap13504dhim-trias-meo-csdap 13455pyraz-mepipe-cno-asppha13505pippy-mepipe-chexo-asppha 13456ibhs-eta2s-imo-aspbzla13506ppy-diphmem-5amo-mezphe 13457imhs-amn2-fo-aval13507nmhs-diphmem-mes-betainyl 13458piraz-dimen-5pho-bsdap13508imhs-m25thiz-cno-betainyl 13459bim-edia2-oem-nzdap13509pyraz-m25oxman2-fo-zdab 13460mam2py-pipa-no2-betainyl13510am2py-pazin-pyo-psdap 13461bz-pipmea-ocho-betadcph135112py-mepazin-nmo-betainyl 13462bhs-pazin-oem-bsdap13512me2py-24thizman2-imo-bnsdap 13463amim-m25thizman2-men-asppha13513fthpym-ms-meto-zdap 13464bhs-eta-imo-mezphe13514dhim-ms-mecpo-tsdap 13515hythpym-diphmem-pyo-betapy13565bim-mepipe-eoco-bhsdap 13516phhs-dis-4pho-betapy13566phpip-din-no1-zdabs 13517ppy-diphmep-meto-bhsdap13567am2py-din-ocho-aspaba 13518am4py-m24thizman2-peo-betapy13568piraz-mea2s-meo-psdap 13519amim-eta-5amo-bsdap13569mam2py-mea-imo-bhsdap 13520menim-pymea-fo-betadcph135702py-mepipe2-sem-nzdab 13521bhs-dipch-men-bnsdap135712py-edian2-ocho-zdap 13522thpym-pnymea-no1-mezphe13572pyr-amo3-mes-mezphe 13523dpam-am3-oem-nbetapy13573impy-pazin-4pho-tsdap 13524bhs-amn2-ocho-bnsdap13574am4py-thizn-mommo-aspaba 13525imhs-edian2-no2-zdap13575mepip-amn3-cnmo-glyzdap 13526bzl-24thiman2-meto-asppha13576thpym-edian2-meo-psdap 13527hythpym-dis-5amo-bsdap13577bim-eta-eoco-zdabs 13528thpym-24thizman2-no1-bhsdap13578impy-diphmem-oem-betadcph 13529ibhs-m24oxman2-cpeo-mezphe13579hythpym-mepazin-mommo-dfzdap 13530deam-amo2-aco-betainyl13580gua-diphmem-eoco-mezphe 135312py-amn2-no1-bsdap13581hythpym-25thiman2-no2-aspaba 13532me-indan2-men-betadcph13582morhs-m25thiz-ocho-bphabs 13533mam2py-pazin-mes-psdapee13583bimhs-dimephmem-napo-zdabs 135342pmhs-diphmep-5pho-zdabs13584mam2py-3pazin-oeto-betapy 13535bhs-pipmeo-no1-zdabs13585nmor-pipa-fo-zdab 13536bim-propn-no2-bnsdap13586me2py-am2-sem-nzdab 13537dhim-hexas-meteto-psdab13587dhim-ams2-fo-glyzdap 13538imhs-amn2-meo-bhsdap13588chmhs-trias-oem-bhsdap 13539pippy-eta2s-5amo-betainyl13589emnim-pnymea-no2-bnsdap 13540impy-trias-fo-bhsdap13590dmbim-dimephmep-meo-csdap 13541npip-diphmem-chexo-glyzdap13591bzl-24thiz-oem-zdab 13542am2py-am2-oem-nzdab13592imhs-pazin-pro-glyzdap 13543pyr-trias-5amo-aspibua13593bimhs-mepazin-meteto-bnsdap 13544bhs-diphmep-meteto-mezphe13594impy-mepipen2-cno-zdap 13545imhs-mepipe-oem-psdab13595piraz-pazin-oem-bhsdap 13546phpip-dimephmep-mmen-13596thpym-m24oxman2-no1-betainyl

betadcph13597dpam-thizn-cpro-glupha 13547phpip-amo2-no2-betadcph13598mam2py-eta-no1-bphabs 13548morhs-dis-no1-betainyl13599fthpym-dimephmep-5pho-betaet 13549chmhs-m24thizman2-men-mezphe13600me2py-n24thiman-oem-psdap 13550moegua-m24thizman2-oeto-13601impy-m25thiz-fo-psdab

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dfzdap13788me-m25thiz-imo-betadcph 13738am2py-2pazin-5amo-csdap13789dmthpym-m24thizman2-mes- 13739imhs-24thiman2-5amo-glyzdapbnsdap 13740bimhs-tetradi-5amo-bphabs13790mam2py-dio-oem-psdab 13741hythpym-diphmep-fo-aspaba137912pmhs-n24thima-no2-zdap 13742chhs-hexas-5amo-mezphe13792thpym-eta-eoco-psdab 13743imhs-pazin-meo-zdab13793am-dimephmem-chexo-zdap 13744amim-amn2-mes-betadcph13794hythpym-edian2-ocho-mezphe 13745ibhs-tridi-meteto-bhsdab13795me2py-24oxman2-5pho-bnsdap 13746thpym-m25thiz-ocho-betadcph137962py-pazin-mes-betapy 13747am4py-m25thiz-emo-aspaba13797bimhs-ams3-napo-zlys 13748npip-pipmeo-men-bhsdab13798me2py-edia2-sem-nbetameph 13749bhs-edian2-imo-csdap13799amim-pazi2n-men-osdap 13750imhs-mepipe-o2-bsdap13800nmor-25thizman2-men-bhsdap 13751thpym-n2nme2n-oem-glyzdap13801tolhs-m24thizman2-pro-bsdap 13752imhs-dipch-cno-ibsdap13802menim-dis-imo-mezphe 13753thpym-amo2-oem-zdap13803phhs-25oxman2-napo-zdap 13754prhs-pymea-napo-betainyl138042py-diphmep-daco-mezphe 13755ibhs-trias-napo-csdap13805bhs-dio-oem-betadcph 13756phpip-pymea-chexo-bnsdap13806amim-props-no1-aval 13757am2py-diphmep-5pho-betainyl13807nim-24thizman2-men-aspibua 13758piraz-m25thiz-no2-mezphe13808bzl-m25thizman2-ocho- 13759mam2py-hexas-fo-aspibuabetainyl 137602py-eta-no2-bsdap138092py-pyma2-napo-psdap 13761deam-mea-peo-aspaba138104pmhs-pazin-fo-zlys 13762thpym-mepipe-oem-zdab13811am2py-amo2-men-dfzdap 13763bimhs-amn2-no1-oxal13812thpym-pipmes-no1-aspibua 13764imhs-ams2-cnmo-glyzdap13813bzl-am2-oem-nzdap 13765am2py-pyma2-ocho-zdap13814me-edian2-no2-zdabs 13766gua-m24oxman2-oem-aval13815piraz-dimephmem-no1-aspbzla 13816hythpym-pnymea-5pho-zdap13867chmhs-dimen-imo-betainyl 13817bz-24oxman2-eoco-glyzdap13868me2py-ams2-chexo-aspibua 13818am2py-mepipen2-no2-bphabs13869imhs-amn2-oem-betapy 13819dhim-mea2s-men-psdab13870piraz-m25thizman2-eoco-zdabs 13820dmbim-mepipe-napo-psdab13871impy-pnymea-napo-bhsdab 13821nmhs-dimephmep-emo-zdab13872hythpym-mepazin-fo-betaet 13822hythpym-diphmem-no1-asppha13873thpym-edian2-meo-bsdap 13823tolhs-din-men-asppha13874moegua-m24thizman2-fo- 13824bimhs-edia2-sem-nbetamephaspibua 13825mepip-amo2-ocho-csdap13875hythpym-dis-men-bhsdab 13826imhs-mepipe-eoco-zdapee13876phhs-trias-chexo-aspibua 13827morhs-25oxman2-no2-csdap13877piraz-mepipe-meo-betapy 13828thpym-mepipe-eoco-betadcph13878me2py-pipa-mes-zlys 13829am2py-tetras-chexo-bnsdap13879hythpym-m25thiz-napo-dfzdap 13830phpip-pipmes-ocho-zdap13880am2py-pyma2-no1-bhsdab 13831am2py-25oxman2-ocho-psdap13881bhs-24oxman2-oem-zdab 13832mam2py-trias-napo-betapy13882mam2py-pipa-no2-zdabs 13833hythpym-dimephmem-meto-13883bim-mepipe-meo-zdab

aspbzla13884imhs-am3-sem-nbetapy 13834bimhs-thizn-mes-ibsdap13885dmam-din-4pho-betapy 13835am2py-thizs-5pho-thizzdap138862py-am3-oem-nbetabnaphth 13836z-thizo-fo-psdap13887amthiaz-trias-cno-aspbzla 13837me2py-mepazin-napo-asppha13888bimhs-edian2-5pho-aspbzla 138382py-ams2-meteto-oxal13889imhs-pazin-meo-psdab 13839pippy-amn3-emo-csdap13890piraz-mepazin-meo-zdap 13840bhs-mepipe-no2-aspbzla13891bim-pazin-eoco-aspbzla 13841n2py-din-no1-oxal13892thpym-dis-no2-psdab 13842thpym-mepazin-5amo-zdabs13893amim-m25thizman2-oem-zdabs 13843hythpym-tetradi-ocho-osdap13894bimhs-tridi-daco-bhsdab 13844am2py-mepipen2-emo-glubzla138954pmhs-pnymea-oem-psdab 13845impy-din-eoco-betaet13896me2py-diphmep-peo-bphabs 13846amim-dis-mes-bhsdap13897imhs-amn2-mes-bsdap 13847amim-mepipen2-oeto-dfzdap13898amim-pnymea-imo-betainyl 13848mam2py-diphmep-imo-zdap13899deam-diaz-mmen-glyzdap 13849piraz-amn3-5amo-bhsdab13900imhs-propn-meo-zdabs 13850bhs-m25thizman2-oem-bphabs13901impy-dis-oem-bsdap 13851bim-m24thizman2-meo-zdab13902imhs-edian2-no2-bnsdap 13852z-dimephmem-5amo-bphabs139032py-thizn-napo-aspibua 13853pippy-dich-chexo-bnsdap13904emnim-m24thiz-eoco-bsdap 13854pippy-diphmep-5amo-bsdap13905dhim-3diaz-aco-aspibua 13855bhs-hexadi-5pho-aspibua13906bhs-eta-oem-bnsdap 13856hythpym-am3-oem-nzdab13907bhs-pazin-no2-psdap 13857bhs-24oxman2-fo-zdabs13908amim-eta-meo-betadcph 13858bim-propa2s-oem-betaet13909piraz-mepipe-meo-psdab 13859ec-24thizman2-4amo-betadcph13910bimhs-eta-hso-aspibua 13860ppy-pnymea-no2-psdab13911piraz-am3-sem-nbetameph 13861thpym-dis-5amo-zdab13912emnim-amo2-no1-bphabs 13862thpym-eta-meo-bsdap13913deam-pyma2-chexo-zdabs 13863bhs-amn3-nmo-glyzdap13914imhs-amn2-meo-psdap 13864piraz-dio-mmen-aspibua13915mam2py-dimen-emo-bsdap 13865amthiaz-tetras-emo-glyzdap13916am2py-din-fo-psdap 13866amthiaz-dis-pheo-mezphe13917am4py-diphmem-meo-aspaba 13918imhs-edian2-oem-bnsdap13969amim-trias-mmen-psdap 13919bim-dimephmep-napo-aval13970bim-dis-meo-betainyl 13920tolhs-ams2-emo-aspibua13971im-mea-meo-betadcph 13921imhs-trias-men-betaet139722py-mepipe-ocho-psdap 13922bim-pazin-daco-bsdap13973nmor-25thizman2-napo-aspibua 13923mam2py-m24thizman2-no1-zdabs13974mam2py-pyma2-mommo-aspibua 13924dmam-ams3-no1-dfzdap13975am2py-24thiz-imo-zdab 13925tolhs-trias-chexo-betainyl13976bhs-din-oem-betainyl 13926phhs-thizo-cnmo-bnsdap13977bimhs-thizn-no1-aspaba 13927edothpym-m24thizman2-13978impy-24thizman2-5amo-bhsdab

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csdap148342py-dimen-5amo-psdap 14835mam2py-thizn-meo-bnsdap14884thpym-mepipe-meo-bnsdap 148362py-mepipen2-eoco-aval14885bhs-amo2-men-psdab 14837dhim-mepipe-mes-asppha14886npip-eta-napo-betainyl 14838emnim-tridi-imo-mezphe14887thpym-tridi-napo-ibsdap 14839mepip-diphmep-mes-mezphe14888nmhs-trias-chexo-bhsdab 14840am2py-thizn-mes-glubzla14889phhs-24thizman2-napo-zdab 148414pmhs-dio-mes-psdap14890me2py-dimen-chexo-bphabs 14842dhim-24thiz-meto-betainyl14891phpip-24thiz-mecpo-asppha 14843hythpym-pazin-4pho-betapy14892menim-edia2-sem-npsdap 14844thpym-m24thizman2-eoco-oxal14893dhim-amo2-men-aspibua 14845pyraz-dimephmep-oem-bphabs148942py-mepipe-ocho-bsdap 14846me2py-dimen-no1-betainyl14895mam2py-pymea-meo-bhsdab 14847hythpym-m25thizman2-napo-14896thpym-eta-eoco-bsdap

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mezphe14904thpym-dimephmep-nol-thizzdap 148542py-eta-meo-psdab14905bhs-din-imo-dfzdap 14855am4py-thizo-no2-zorn14906piraz-amn2-eoco-betaet 14856thpym-mepipe-meo-betainyl14907bim-m24oxman2-cpro-zdap 14857amim-pipa-5pho-bsdap149082py-eta-meo-bnsdap 14858bim-mepipe-5pho-zdab14909me2py-tridi-chexo-asppha 14859bim-pyma2-men-mezphe14910me2py-25thizman2-imo-zdabs 14860mepip-24thizman2-aco-dfzdap14911npip-m24thiman2-men-psdap 14861thpym-ams3-no1-dfzdap14912hythpym-amn3-peo-dfzdap 148622pmhs-25oxman2-napo-bhsdab14913mepip-m24thizman2-napo- 14863hythpym-dimephmem-imo-zdabasppha 14864piraz-24thizman2-meto-betapy14914imhs-ams2-ocho-csdap 14865pippy-diphmep-eoco-glyzdap14915gua-ams2-eoco-aspbzla 14866pyraz-tridi-mecpo-mezphe14916phpip-pipmea-cpeo-bphabs 14867amim-dis-5amo-thizzdap14917bimhs-diphmep-cpeo-bsdap 14868emnim-tetradi-pyo-bhsdab14918imhs-eta-oem-bhsdap 14869piraz-mepipe-fo-zdabs14919prhs-amn2-no2-bnsdap 14870amim-pipa-cno-csdap14920gua-24thiz-meo-tsdap 14871me2py-ams2-cno-betapy14921amthiaz-diphmep-5amo-aspbzla 14872ec-tetradi-5amo-zdap14922bhs-amn2-emo-zdap 14873gua-amo3-no1-bnsdap14923amim-trias-5pho-thizzdap 14874bimhs-mea-emo-glyzdap14924menim-mepazin-emo-betainyl 14875pippy-hexadi-imo-betainyl14925dmam-mepipe-men-csdap 14876mam2py-tetradi-eoco-dfzdap149262py-eta-ocho-psdap 14877emnim-hexas-4pho-bhsdab14927pyr-butn-emo-zdapee 14878fthpym-din-4amo-bhsdap14928bim-thizn-meteto-bphabs 148792pmhs-dimephmep-meteto-14929bimhs-dimephmep-pheo-bsdap

aspbzla14930bim-trias-men-bsdap 14880mam2py-pipmea-daco-betainyl14931am2py-edia2-oem-npsdap 14881me2py-amo2-ocho-glyzdap14932am2py-dimephmep-napo- 14882bim-amn2-mes-psdapbetadcph 14883mam2py-amo2-napo-betadcph14933impy-thizn-oeto-betadcph 14934thpym-mepipe-no2-glupha14985dpam-mepazin-chexo-zdab 14935hythpym-24thizman2-fo-bhsdap14986mam2py-diphmep-meteto- 14936gua-n2o2n-emo-csdapaspbzla 149372py-mepipe-meo-betapy14987piraz-thizn-no1-asppha 14938gua-pazin-men-aspbzla14988phpip-pipmeo-napo-bhsdap 14939impy-25oxman2-imo-betadcph149892py-eta-no2-bnsdap 14940tolhs-diphmep-imo-bhsdab14990phhs-dimephmep-men-dfzdap 14941deam-edia2-oem-nbeta34-14991pippy-pyma2-chexo-psdapee

dimeoph149922pmhs-thizn-5amo-glyzdap 14942imhs-dis-no2-zdap14993am2py-pazin-4pho-bsdap 14943imhs-pipmea-men-ppsdap14994hythpym-eta-eoco-osdap 14944dhim-dimen-5amo-betainyl14995edothpym-din-eoco-bnsdap 14945piraz-n2nme2n-ocho-zdab14996imhs-eta-5pho-psdab 14946deam-dimen-fo-bphabs149972py-pnymea-pyo-betainyl 14947impy-amn2-pyo-glupha14998ec-dis-no1-bhsdap 14948chhs-mea2s-napo-zdap14999ppy-amo2-paco-bhsdap 14949bhs-indan2-5pho-zdabs15000deam-mepipe-emo-asppha 149502py-dimephmem-meo-glyzdap150012py-trias-mmen-psdab 14951bim-eta-oem-bhsdap15002dmam-m25thiz-chexo-zdap 14952morhs-dimephmep-pyo-bsdap15003impy-ams2-aco-psdap 14953bimhs-edia2-sem-nbetapy15004pyr-pymea-meo-psdab 14954npip-m25thiz-imo-glubzla15005bimhs-mepipen2-mes-zdab 149552py-pazin-no2-psdap15006phhs-dimephmem-eoco-bphabs 14956moegua-pipmea-imo-zdabs15007pippy-m24thizman2-meo-bhsdab 14957nmhs-pipa-5amo-asppha15008pippy-n24thiman-mommo-mezphe 14958deam-pymea-eoco-betaet15009pippy-amn3-oem-psdap 14959bimhs-amo2-fo-bsdap15010piraz-amo3-pheo-zdap 14960impy-tridi-ocho-bsdap15011bim-diphmep-oem-psdab 14961thpym-edian2-5pho-psdap15012bzl-ms-emo-psdapee 14962thpym-mepipen2-5amo-psdab15013bim-pazin-no1-bsdap 14963bimhs-pyma2-aco-zdabs15014piraz-thizn-5amo-zdap 14964me2py-propn-no1-csdap15015bhs-pazin-5pho-betapy 14965imhs-pymea-eoco-dfzdap15016mam2py-dis-5amo-betadcph 14966nim-pazin-oem-mezphe15017imhs-m24thizman2-cnmo- 14967n2py-mepipe-pheo-zdapbetainyl 149682py-m25thiz-meo-bhsdap15018mam2py-pipmea-no2-aspbzla 14969me2py-pnymea-imo-tsdap15019phpip-pnymea-mes-csdap 14970bim-tetradi-5pho-bsdap15020am-thizn-no1-betainyl 14971thpym-pymea-chexo-psdab15021imhs-propa2s-mmen-bnsdap 14972imhs-amn3-eoco-mezphe15022gua-pipa-no2-aval 149732py-mepipe2-sem-npsdap15023am4py-pnymea-mes-psdab 14974cl3pyme-pazi2n-fo-zorn15024imhs-am3-oem-nbetapy 14975imhs-dis-hso-glyzdap15025impy-ams2-oeto-zdab 14976phhs-mepazin-men-psdab15026imhs-din-meo-glubzla 14977bim-amn3-imo-dfzdap15027bzl-tetradi-daco-betapy 14978am-pazi2n-mommo-zdabs15028hythpym-n2o2n-fo-dfzdap 14979hythpym-dimen-no1-psdapee15029nmhs-m24thizman2-eoco- 14980impy-mepipe-cnmo-bphabsglyzdap 14981am2py-dimephmep-hso-glyzdap15030pippy-trias-emo-betainyl 14982imhs-mepipe-chexo-betainyl15031am4py-dimephmem-chexo-psdap 14983impy-propa2s-baeo-bhsdap15032thpym-pazin-mes-bsdap 14984hythpym-amo2-ocho-betapy15033bim-tridi-ocho-glubzla 15034bim-24thiz-men-zdap15086am4py-edian2-meo-bhsdap 150352pmhs-amn3-imo-mezphe15087pippy-24oxman2-oem-mezphe 15036am2py-tetradi-oem-psdab15088phpip-24thiz-eoco-dfzdap 15037ec-dimephmep-pyo-dfzdap15089bim-pazin-meo-zdab 15038menim-edian2-meo-psdap15090morhs-pipa-5pho-zdab 15039bimhs-24thiman2-mommo-betapy15091am2py-tridi-nmo-aspbzla 15040z-eta2s-eoco-zdab15092ibhs-m24thizman2-fo-dfzdap 15041bhs-eta-oem-aspibua15093pyr-dis-chexo-asppha 150422py-dimephmep-chexo-betapy15094thpym-pymea-no2-zlys 15043am2py-mepipen2-meo-ppsdap15095am2py-m25thiz-5amo-zdab 15044bhs-eta-oem-zdap15096piraz-thizn-emo-betapy 150452py-mepipe-oem-psdab15097z-pyma2-cno-psdab 15046bimhs-amn2-oem-zlys15098am4py-m24thiz-mes-betainyl 15047pyr-pipa-daco-psdap15099bim-edian2-eoco-zdap 15048bim-diphmem-men-psdapee15100piraz-eta2s-hso-mezphe 15049impy-pnymea-men-psdab15101impy-eta-paco-glyzdap 15050bz-amo3-4amo-bphabs15102mam2py-dis-chexo-zdab 15051dmam-mepipen2-4amo-zdap15103pyraz-pyma2-eoco-psdab 15052bhs-eta-pyo-bhsdap15104dpam-edian2-men-bhsdap 150532py-edian2-5pho-bhsdap15105bimhs-dipch-oem-asppha 15054dhim-m24thizman2-oeto-bhsdab15106am2py-3pazin-oeto-psdapee 150552py-m25thiz-oeto-glyzdap15107bhs-edian2-mes-bsdap 15056bimhs-m25thizman2-meo-zlys15108bimhs-am3diaz-pyo-bphabs 15057bhs-m24thizman2-cpeo-aval15109me2py-am3diaz-mecpo-zdap 15058imhs-trias-chexo-dfzdap15110bim-pazin-5pho-psdap 15059phpip-amn2-meo-psdab15111dmam-mepipe-chexo-betadcph 15060gua-hexadi-mommo-betapy15112am4py-mea2s-napo-csdap 150612py-amn2-meo-bsdap15113pippy-dipch-meto-bnsdap 150622py-tetradi-cpeo-zdab15114am2py-trias-oem-dfzdap 15063mepip-butn-5pho-zdab15115hythpym-pentadi-no2-dfzdap 15064pippy-amn2-no1-zdabs15116prhs-amn2-chexo-asppha 15065bimhs-mea-ocho-mezphe15117prhs-dis-napo-psdab 15066dmbim-diphmem-oem-bphabs15118bimhs-din-pro-aspibua 15067thpym-mepipe2-oem-nbetapy15119nmor-pymea-peo-csdap 15068gua-tetradi-nmo-psdap15120dhim-amn3-5pho-zlys 15069pippy-dis-chexo-bhsdap15121me2py-dimephmem-imo-glyzdap 15070hythpym-pyma2-fo-zdab15122piraz-edian2-paco-dfzdap 15071piraz-amn3-fo-mezphe15123pippy-mepipen2-napo-zdabs 15072bhs-mepipen2-meteto-psdab15124bhs-amn3-peo-asppha 15073pyr-25oxman2-fo-thizzdap15125dmthpym-amo2-napo-psdab 15074am2py-25oxman2-baeo-zdap15126chhs-25oxman2-oem-betainyl 15075ibhs-am3diaz-no1-bhsdab15127menim-thizn-5amo-bphabs 15076dhim-pentas-meto-aspbzla15128npip-mepipen2-mes-zdabs 15077dhim-din-eoco-aspibua15129imhs-dimen-mes-thizzdap 15078bhs-pyma2-eoco-glyzdap151302py-pyma2-men-aspibua 15079me-ams2-fo-betainyl15131amim-am2-sem-nbetapy 15080mam2py-amn2-ocho-bsdap15132am2py-m24thiz-eoco-aspbzla 15081bim-amn2-eoco-bhsdap15133dhim-mepipe-no2-bsdap 15082cl3pyme-am3-sem-nbetapy15134bz-mepipe2-sem-nbeta34- 15083piraz-pymea-imo-zdapdimeoph 15084bimhs-mepazin-5amo-bhsdap15135thpym-m24thizman2-eoco-zdab 15085bhs-dimephmep-emo-glyzdap15136dhim-eta2s-hso-asppha 15137emnim-din-chexo-zdabs15155dmthpym-n2o2n-mes-psdab 15138impy-pentadi-meo-betapy15156bim-amn2-no1-psdap 151392py-mea-fo-mezphe15157thpym-indan2-no1-betapy 15140imhs-eta-no2-betapy15158mam2py-24thiz-hso-aspibua 15141pyrhs-eta-aco-psdap15159bimhs-pipmes-no2-mezphe 15142dhim-m24thizman2-napo-aval15160piraz-tridi-pheo-psdab 15143impy-pazin-mes-mezphe15161mam2py-amn2-5pho-zdab 15144imhs-pentadi-eoco-betainyl15162imhs-amn2-no1-psdab 15145thpym-n24thiman-imo-bnsdap15163dhim-pyma2-5amo-betainyl 15146dhim-dis-no2-glyzdap15164me2py-dipch-chexo-zdap 15147ec-pyma2-oem-aspbzla15165ec-thizn-cpeo-mezphe 15148npip-diphmem-men-aspibua15166mam2py-am2-oem-nbetapy 15149piraz-mepipen2-eoco-osdap15167tolhs-dimephmem-pro-bphabs 15150gua-pipa-fo-aspaba15168z-mepipen2-peo-zdab 15151im-amn3-no2-bnsdap15169pippy-edian2-5pho-bhsdap 15152bhs-ams2-meo-zdabs15170amim-edian2-5pho-mezphe 15153hythpym-edian2-men-bphabs 15154bim-pyma2-mes-bhsdap

在上表中使用了结构单元A、E、G和L的下列缩写

通常使用本领域技术人员已知的有机化学的方法，如标准著作例如 Houben-Weyl，“有机化学方法”(MethodenderOrganischenChemie)、 Thieme-Verlag、Stuttgart或March“高级有机化学”(AdvancedOrganic Chemistry)、第四版，Wiley&Sons所述，制备式I的化合物和制备它 们所需的原材料。另外，进一步的制备方法还描述于R.Larock，“综合 有机转化”(ComprehensiveOrganicTransformations)，Weinheim1989 中，特别是制备烯烃、炔、卤化物、胺、醚、醇、酚、醛、酮、腈、羧 酸、酯、酰胺和酰氯。为功能基团选择适宜的保护基团和此保护基团的 引入或去除，描述于例如Greene和Wuts，“有机合成的保护基团” (ProtectiveGroupsinOrganicSynthesis)第2版，Wiley&Sons， 1991中。

可以在溶液或聚合物载体上进行式I化合物的合成，在每种情况下所 用的反应条件是那些对于相应的反应已知并且适宜的反应条件。而且， 还可以使用在此处未提及的但是是本身已知的方案。

I型化合物的一般合成，其中如上所述，A-E-可以是结构元素B-，而- U-T可以是结构元素-L，描述于方案1至7中。除非另有说明，所有原材 料和试剂均可以购买或用常规方法从可以购买的前体制备。

例如，从作为中间体的通式II的相应取代的4-硫代-3，4-二氢嘧啶-2 (1H)-酮开始，合成通式I的化合物。II型的4-硫代-3，4-二氢嘧啶-2 (1H)-酮是已知的并且可以通过例如在Katritzky和Rees，“综合杂 环化学”(ComprehensiveHeterocyclicChemistry)，Pergamon出版， 第3卷；第135-139页和在其中引用的文献中所述的已知方法制备。

合成4-硫代-3，4-二氢嘧啶-2(1H)-酮的优选方法包括，例如，将 烯胺加成至异硫氰酸酯上并随后环化，如Goerdeler等，在化学通讯(Chem. Ber.)1963，第526-533页和Chem.Ber.1965，第1531-1542页中所 述。4-硫代-3，4-二氢嘧啶-2(1H)-酮的制备特别优选根据Lamon在杂 环化学杂志1968，5，837-844中所述的方法进行，此方法是基于烯胺与 烷氧基-或芳氧基羰基异硫氰酸酯的反应。可以通过通式III的相应的烯 胺衍生物(其中X优选为吗啉、吡咯烷或哌啶基)与伯胺反应，同时生 成取代的4-硫代-3，4-二氢嘧啶-2(1H)-酮II(方案1)，来完成式I化 合物的合成。 方案1 如上所述，SG1是羧基官能团的保护基，或SG1-OOC-残基是T。

在固相上，例如通过使用羧酸官能团作为连接基，连接于一种固体载 体上(SG1＝固体载体)，进行合成特别有效。例如由Bunin在“The CombinatorialIndex”(AcademicPress，1998)中，详细描述了固相 合成的方法。在U含有另一个官能团或氨基酸的侧链(该氨基酸含有一 个所谓的侧链官能度)的情况下，则通过适宜的保护基团对它们加以保 护是有益的。

为了进一步反应，用标准方法通过加入一种碱，将通式II化合物中的 4-硫代基烷基化。作为碱可以使用一种碱金属或碱土金属氢化物如氢化 钠、氰化钾或氢化钙，一种碳酸盐例如碱金属碳酸盐如碳酸钠或钾，一 种碱金属或碱土金属氢氧化物如氢氧化钠或钾，一种醇化物例如甲醇钠、 叔丁醇钾，一种金属有机化合物例如丁基锂或碱金属氨化物例如二异丙 基氨基锂、双(三甲基甲硅烷基)氨基锂、钠或钾，叔胺例如三乙胺、1， 8-二氮杂双环[5.4.0]十一碳-7-烯或乙基二异丙胺。特别优选使用碱金 属碳酸盐例如Cs2CO3或叔胺例如乙基二异丙胺。

在通式I的化合物中的UE是氧或NRE2的情况下，或在h＝0，没有UE， 并且因此A-E片段和G片段之间通过一个存在于片段中的N基团直接连 接的情况下，优选将4-硫代基转化为相应的硫氰酸酯，这是通过使用溴 化氰的烷基化完成的，例如如四面体通讯(TetrahedronLetters)1991， 32(22)，2505-2508中所述(方案II)。然后可以将式IVa的硫氰酸酯 与通式A-E-(UE)h-H(V)的适宜的胺或醇，用本领域技术人员已知的方 法反应，需要的话加入一种碱，获得通式VI的化合物(方案II)。在此方 案中，为了说明，-E’-代表没有(UE)h连接单元的空间结构单元E。

在通式I的化合物中的UE残基是硫的情况下，可以直接使用一种通式 A-E-Y(VII)化合物作为烷化基剂，在通式A-E-Y(VII)中，基团Y是 一种常规的离去基团例如卤素如氯、溴、碘或可以被卤素、烷基或卤烷 基取代的芳基或烷基磺酰基，例如甲苯磺酰基、三氟甲烷磺酰基和甲基 磺酰基或另一种等效的离去基团(方案II)。

UE＝硫的通式I的化合物的另一种优选的制备方法，是将通式II的化合 物转化为相应的硫基乙腈(IVb)，然后它可以与结构式A-E-SH的硫醇(Vb) 反应得到化合物VI。

在标准条件下，去除保护基团SG1(参见下文)，产生通式I的化合物。 在SG1是C1-C4烷基或苄基，或SG1-OOC-是T的情况下，通式VI的化合物 直接对应于I型化合物。 方案2

可以用作保护基团SG的是所有从事肽合成的技术人员已知的和惯用 的保护基团，如其还描述于标准著作例如Bodanszky“肽合成实践(The PracticeofPeptideSynthesis)”，第二版，Springer-Verlag1994 和Bodanszky“肽合成原理”(PrinciplesofPeptideSynthesis)， Springer-Verlag1984中。同样地，在本领域技术人员已知并例如由 Greene和Wuts描述于“有机合成的保护基团”，第2版，Wiley&Sons， 1991中的条件下，进行式VI化合物中保护基团和用于制备化合物V和VII 所用的保护基团的去除。

优选使用的氨基保护基团是Boc、Fmoc、苄氧基羰基(Z)、乙酰基、 三苯甲基或Mtr。所用的酸保护基团例如有SG1，优选C1-C4-烷基，例如 甲基、乙基、叔丁基或苄基或三苯甲基，或以市售聚苯乙烯树脂的形式 存在的结合聚合物的保护基团，例如2-氯三苯甲基氯树脂或Wang树脂 (由Bachem或Novabiochem供应)。

对酸不稳定的保护基团(例如Boc、叔丁基、Mtr、三苯甲基)的除去， 根据所使用的保护基团，可使用有机酸例如三氟乙酸(TFA)、三氯乙酸、 高氯酸、三氟乙醇，磺酸例如苯-或对-甲苯磺酸，或无机酸例如盐酸、 或硫酸来进行，通常过量使用酸。

在三苯甲基的情况下，加入硫醇例如茴香硫醚或苯硫酚是有益的。额 外存在惰性溶剂是可能的但不总是需要。适宜并优选的惰性溶剂是有机 溶剂例如羧酸如乙酸、醚如THF或二噁烷、酰胺如DMF或二甲基乙酰胺、 卤代烃如二氯甲烷、醇如甲醇、异丙醇或水。上述溶剂的混合物也是适 宜的。这些反应的温度在10℃至50℃，优选的范围为0℃至30℃。

通过用有机胺例如以5-50％CH2Cl2或DMF溶液形式存在的二甲胺、二 乙胺、吗啉、哌啶处理，使对碱不稳定的保护基团发生裂解。这些反应 的温度在10℃至50℃，优选的范围为0℃至30℃。

酸保护基团例如甲基或乙基的裂解优选通过在一种惰性溶剂中的碱性 水解来进行。优选使用的碱为：碱金属或碱土金属氢氧化物，优选NaOH、 KOH或LiOH。所使用的溶剂是所有常规的惰性溶剂，例如，烃如己烷、 庚烷、石油醚、甲苯、苯或二甲苯，氯化烃如三氯乙烯、1，2-二氯乙烷、 四氯甲烷、氯仿、二氯甲烷，醇如甲醇、乙醇、异丙醇、正丙醇、正丁 醇或叔丁醇，醚如二乙醚、甲基叔丁基醚、二异丙醚、四氢呋喃、二噁 烷，乙二醇醚如乙二醇单甲醚或单乙醚、乙二醇二甲醚，酮如丙酮、丁 酮，酰胺如二甲基甲酰胺(DMF)、二甲基乙酰胺或乙酰胺，腈如乙腈， 亚砜如二甲基亚砜、环丁砜、N-甲基吡咯烷酮、1，3-二甲基四氢-2(1H) -嘧啶酮(DMPU)、1，3-二甲基-2-咪唑烷酮，硝基化合物如硝基甲烷或 硝基苯，水或上述溶剂的混合物。根据所使用的溶剂或溶剂的混合物， 添加相转移催化剂可能是有益的。这些反应的温度通常在-10℃至100℃。

可以通过氢解去除的保护基团，例如苄氧基羰基(Z)或苄基，可例 如通过在催化剂(例如一种在作为载体的活性碳上的贵金属)存在下的 氢解而去除。适宜的溶剂如上文所描述，特别是醇如甲醇或乙醇，酰胺 如DMF或二甲基乙酰胺，酯如乙酸乙酯。氢解通常在1至200巴的压力、 0℃至100℃的温度下进行；添加酸如乙酸或盐酸可能是有益的。优选使 用活性碳上的5-10％的Pd作为催化剂。

E型的结构单元通常用本领域技术人员已知的方法构建。所用的结构 单元或是可购买的或可用文献中的已知方法获得的。某些这种结构单元 的合成在实施例部分以示例的方式加以描述。

在V型和VII型化合物中存在的片段QE是杂芳基的情况下，所用的结构 单元是购买的或用文献中的已知方法获得的。大量的制备方法详细地描 述于Houben-Weyl的“有机化学方法”(E6卷：呋喃、噻吩、吡咯、吲哚、 苯并噻吩、-呋喃、、-吡咯；E7卷：喹啉、吡啶；E8卷：异噁唑、噁唑、 噻唑、吡唑、咪唑和它们的苯并稠合的代表，和噁二唑、噻二唑和三唑；； E9卷：哒嗪、嘧啶、三嗪、氮杂和它们的苯并稠合的代表，和嘌呤)。

通式化合物： HNRE1-(CRE3RE4)k1-(LE)k2-(CRE5RE6)k3-(QE)k4--(CRE7RE8)k5-(TE)k6-(CRE9RE10)k7-(UE)h-DE(VIII) NC-(CRE3RE4)k1-(LE)k2-(CRE5RE6)k3-(QE)k4--(CRE7RE8)k5-(TE)k6-(CRE9RE10)k7-(UE)h-DE(IX) 转化为通式化合物： A-(CRE3RE4)k1-(LE)k2-(CRE5RE6)k3-(QE)k4--(CRE7RE8)k5-(TE)k6-(CRE9RE10)k7-(UE)h-DE(X) A-(CRE3RE4)k1-(LE)k2-(CRE5RE6)k3-(QE)k4--(CRE7RE8)k5-(TE)k6-(CRE9RE10)k7-(UE)h-DE(XI)

可用本领域技术人员的已知方法，例如WO97/08145中所述的方法完 成。式VIII至XI中的基团DE代表H或NSG2基团。直接或在去除了相应的 保护基团SG2之后，这些结构单元可以转化为通式I的化合物(方案II)。

方案3至7以示例的方式描述了大量引入A的方法，每种情况下所用 的反应条件对于相应反应来说是已知的并适宜的反应条件。而且还可以 使用本身已知的但未在此提及的案。

脲和硫脲(AE-1至AE-3)可以用有机化学的常规方法制备，例如通 过将异氰酸酯或异硫氰酸酯与一种胺，需要的话在一种惰性溶剂中在加 热下反应(Houben-Weyl，第VIII卷，157以下页)(方案3)。

方案3

方案4以示例的方式显示了AE-4型化合物的制备，如例如由Blakemore 等在欧洲药物化学杂志，1987(22)2，91-100，或由Misra等在Bioorg. Med.Chem.Lett.19944(18)，2165-2170中所述。

方案4

通式AE-5和AE-6的未取代的或环胍衍生物，可以用可购买的或可以 简单地获得的试剂制备，如例如Synlett1990，745，有机化学杂志，1992， 57，2497，Bioorg.Med.Chem.1996，6，1185-1208；Bioorg.Med.Chem. 1998，1185，或Synth.Comm.1998，28，741-746中所述。

通式AE-7的化合物，可以用与US3,202,660相似方法制备，通式 AE-9、AE-10、AE-11和AE-12的化合物，可以用与WO97/08145的相似 方法制备。通式AE-8化合物的制备显示于方案5中，例如可以使用Perkins 等TetrahedronLett.1999，40，1103-1106中所述的方法制备。方案 5总结了上述化合物的合成。 ＝稠合的环系如芳基或杂芳基

通式AE-13的化合物，可以用类似于Froeyen等，PhosphorusSulfur SiliconRelat.Elem.1991，63，283-293的方法制备。通式AE-14的化 合物，可以用类似于Yoneda等，Heterocycles1998，15N’-1，Spec.Issue， 341-344的方法制备(方案6)。相应的化合物还可以用类似于WO97/36859 的方法制备：

方案6

通式AE-15的化合物的制备如Synthesis1981，963-965，或Synth. Comm.1997，27(15)，2701-2707所述。通式AE-16的化合物，可以用 类似于有机化学杂志1991，56(6)，2260-2262的方法制备(方案7)。

方案7 ＝稠合的环系如芳基、杂芳基、环烷基

Ex＝-(CRx3Rx4)k1-(Ik)k2-(CRx5Rx6)k3-(Qx)k4-(CRx7Rx8)k5-(Tx)k6-(CRx9Rx10)k7-

本发明还涉及式IGL结构单元用于制备与整合素受体结合的化合物的 用途

-G-LIGL

本发明还涉及含有式IGL结构单元的药物。

本发明还涉及药物制剂，除了常规药物赋形剂外，它还包含至少一种 式I的化合物。

可通过常用的方法经口服或胃肠外(皮下、静脉、肌内、腹膜内)应 用本发明的化合物。也可通过鼻咽以蒸汽或喷雾的形式给药。还可以将 本发明的化合物直接与相关组织接触给药。

根据患者的年龄、状况、体重和给药方式确定剂量。口服给药时活性 成分每日的剂量通常在0.5至50mg/kg体重之间，胃肠外给药时在0.1 至10mg/kg体重之间。

可用常规的固体或液体的药物形式应用此新的化合物，例如无包衣或 薄膜包衣的片剂、胶囊、粉剂、颗粒剂、糖衣丸、栓剂、溶液、软膏、 霜剂或喷雾剂等。这些药物形式可用常规的方法制备。为了制备这些药 物形式，可将活性成分与常见的药物辅剂一起进行处理。这些药物辅剂 例如为片剂粘合剂、填充剂、防腐剂、片剂崩解剂、流动调节剂、增塑 剂、湿润剂、分散剂、乳化剂、溶剂、释放延缓剂、抗氧化剂和/或推进 气体(参见H.Sucker等：PharmazeutischeTechnologie，Thieme-Verlag， Stuttgart，1991)。如此获得给药形式的活性成分的含量通常为其重量 的0.1至90％。

本发明还涉及式I化合物在治疗疾病的药物制备方面的应用。式I化 合物可用于治疗人或动物的疾病。式I化合物与整合素受体结合。因此 它们优选适于充当整合素受体配体，并适用于制备治疗与整合素受体相 关的疾病的药物，特别适用于治疗这样的疾病，其中整合素与其天然受 体之间相互作用失调，即出现增强或下降。

整合素受体配体指激动剂和拮抗剂。

相互作用的增强或下降指天然配体和/或整合素受体表达的增强或下 降，因此也指天然配体和/或整合素受体数量的增加或下降，或天然配体 对整合素受体亲和力的增强或下降。

与正常状态相比，存在整合素及其天然受体之间相互作用调节障碍的 情况，也就是说当这种调节障碍不能与生理状态相一致时，出现相互作 用的增强或下降。其相互作用的增强或下降可导致生理病理状态。

导致生理病理状态的调节障碍的水平依赖于单个机体和疾病的性质和 位置。

可适用本发明式I化合物的整合素受体优选为α5β1、α4β1、αvβ5和αvβ3 整合素受体。

特别优选的是式I化合物与αvβ3整合素受体结合，因此它们可特别优 选地充当αvβ3整合素受体的配体，并且可用于治疗αvβ3-整合素受体和其 天然配体之间相互作用增强或下降的疾病。

式I化合物特别优选地用于下面疾病的治疗：

诸如动脉粥样硬化、血管损伤或斯坦特固定模移植 (Stentimplantation)后的再狭窄和血管成形术(新内膜形成、平滑肌 细胞移位和增生)等的心血管疾病，

急性肾衰竭，

诸如糖尿病性血管病或视网膜病或者类风湿性关节炎的血管生成相关 的微血管病，

血小板介导的血管闭塞、动脉血栓，

中风、心肌梗塞或中风后的再灌注损害，

诸如肿瘤转移或肿瘤生长(肿瘤引起的血管生成)的癌，

骨质疏松症(破骨细胞趋化和粘附至骨基质后的骨吸收)，

高血压、牛皮癣、甲状旁腺机能亢进、佩吉特病、恶性高血钙、转移 性溶骨损害、炎症、伤口愈合、心衰、充血性心衰(CHF)，并可用于抗 病毒、抗真菌、抗寄生虫或抗细菌的治疗和预防(吸附和内在化)。

为了在许多适应症中提高疗效，将式I化合物与至少一种其它化合物 联合用药是有优势的。这些其它化合物的作用机制可与式I化合物相同 或不同。

因此除了式I化合物和常规药物赋形剂外，此药物制剂还可包含至少 一种其它的化合物，根据下面10组中的适应症来确定其选择。 1组：

治疗血小板介导的血管闭塞或血栓的药物：

血小板粘附、活化或聚集抑制剂，诸如乙酰水杨酸、乙酰水杨酸赖氨 酸、吡拉西坦(Pilacetym)、双嘧达莫、阿昔单抗(Abciximab)、血栓 烷拮抗剂、诸如Tirofiban等的纤维蛋白原拮抗剂，或者诸如噻氯匹定 或氯吡格雷(Clopidogrel)的ADP所致聚集的抑制剂，

降低凝血酶活性或阻止凝血酶形成的抗凝剂，诸如IIa、Xa、XIa、IXa 或VIIa抑制剂、血小板活化化合物拮抗剂和选择蛋白拮抗剂，或者 2组：

治疗心肌梗塞或中风的药物：

血小板活化或聚集抑制剂，诸如GPIIb/IIIa拮抗剂、凝血酶抑制剂 或者Xa因子抑制剂或者ADP受体拮抗剂，

丝氨酸蛋白酶抑制剂，

减少纤维蛋白原的化合物，

选择蛋白拮抗剂，

ICAM-1或VCAM-1拮抗剂，

白细胞粘附抑制剂，

血管壁血细胞外渗抑制剂，

纤维蛋白溶解调节化合物，诸如链激酶、tPA、纤维蛋白溶解酶原活 化刺激剂、TAFI抑制剂、XIa抑制剂或PAI-1拮抗剂，

补体因子抑制剂，

内皮素受体拮抗剂，

酪氨酸激酶抑制剂，

抗氧化剂和

白介素8拮抗剂，或者 3组：

治疗充血性心力衰竭的药物：

内皮素拮抗剂，

ACE抑制剂，

血管紧张素受体拮抗剂，

内肽酶抑制剂，

β阻滞剂，

钙通道阻滞剂，

磷酸二酯酶抑制剂和

Caspase抑制剂，或者 4组：

治疗血管损伤或斯坦特固定模移植后的再狭窄的药物：

凝血酶抑制剂，

Xa因子抑制剂，

引起凝血酶形成的凝血途径的抑制剂，诸如肝素或低分子量肝素，

血小板粘附、活化或聚集抑制剂，诸如GPIIb-IIIa拮抗剂或者vWF 或GPIb介导的血小板粘附和活化拮抗剂，

内皮素受体拮抗剂，

氧化氮合成酶抑制剂，

CD44拮抗剂，

选择蛋白拮抗剂，

MCP-1拮抗剂，

增殖细胞中信号转导抑制剂，

EGF、PDGF、VEGF或bFGF介导的细胞反应的拮抗剂和

抗氧化剂，或者 5组：

治疗糖尿病性血管病的药物：

EGF、PDGF、VEGF或bFGF介导的细胞反应的拮抗剂，

肝素或低分子量肝素或者其它GAGs，

MMPs抑制剂，

选择蛋白拮抗剂，

内皮素拮抗剂，

ACE抑制剂，

血管紧张素受体拮抗剂和

糖基化抑制剂或AGE形成抑制剂或AGE阻滞剂和它们受体的拮抗剂， 诸如RAGE，或者 6组：

治疗动脉粥样硬化的药物：

降脂化合物，

选择蛋白拮抗剂，

ICAM-1或VCAM-1的拮抗剂，

肝素或低分子量肝素或者其它GAGs，

MMPs抑制剂，

内皮素拮抗剂，

载脂蛋白A1拮抗剂，

胆固醇拮抗剂，

HMG-CoA还原酶抑制剂，

ACAT抑制剂，

ACE抑制剂，

血管紧张素受体拮抗剂，

酪氨酸激酶抑制剂，

蛋白激酶C抑制剂，

钙通道阻滞剂，

LDL受体功能刺激剂，

抗氧化剂，

LCAT模拟物和

自由基清除剂，或者 7组：

治疗癌症的药物，优选抑制肿瘤生长或转移的药物：

抑制细胞生长或抗肿瘤的化合物，

抑制增殖的化合物，诸如激酶抑制剂和

肝素或低分子量肝素或者其它GAGs，或者 8组：

治疗骨质疏松症的药物：

抗吸收治疗的化合物，

激素替代治疗的化合物，诸如雌激素或孕酮拮抗剂，

重组人生长激素，

双膦酸酯，诸如阿仑特罗，

用于降钙素治疗的化合物，

降钙素刺激剂，

钙通道阻滞剂，

骨形成刺激剂，诸如生长因子兴奋剂，

白介素6拮抗剂和

Src酪氨酸激酶抑制剂，或者 9组：

治疗类风湿关节炎的药物：

TNF拮抗剂，

VLA-4或VCAM-1拮抗剂，

LFA-1、Mac-1或ICAMs拮抗剂，

补体抑制剂，

免疫抑制剂，

白介素-1、白介素-5或白介素-8拮抗剂和

二氢叶酸还原酶抑制剂，或者 10组：

促进伤口愈合的药物：

胶原酶，

PDGF拮抗剂和

MMPs。

一种包含至少一种式I化合物、任选的药物赋形剂和取决于适应症的 每种情况下选自上述各组中的至少一种其它化合物的药物制剂，是指将 至少一种式I化合物与在每种情况下选自上述各组中的至少一种其它化 合物和任选的药物赋形剂联合给药。

可通过包含至少一种式I化合物、任选的药物赋形剂和根据上述各组 所列的适应症选择的至少一种其它化合物进行联合给药。这种联合给药 也可在空间上和/或时间上分开进行。

为了在空间上和/或时间上分开给药，可将这种药物制剂的组分式I 化合物和选自上述各组的化合物在空间上和/或时间上分开给药。

治疗血管损伤或斯坦特固定模移植后的再狭窄时，可在相关部位局部 单独应用式I化合物，或者与选自4组中的至少一种化合物联合应用。 用这些化合物包裹斯坦特固定模也可能是有利的。

治疗骨质疏松症时，式I化合物与抗吸收或激素替代治疗联合应用可 能是有利的。

本发明也相应地涉及前面所述药物制剂在制备治疗疾病的药物中的应 用。

在一个优选实施方案中，本发明涉及前面所述联合药物制剂在制备治 疗疾病的药物中的应用，这些疾病为：

1组化合物所治疗的血小板介导的血管闭塞或血栓，

2组化合物所治疗的心肌梗塞或中风，

3组化合物所治疗的充血性心力衰竭，

4组化合物所治疗的血管损伤或斯坦特固定模移植后的再狭窄，

5组化合物所治疗的糖尿病性血管病，

6组化合物所治疗的动脉粥样硬化，

7组化合物所治疗的癌症，

8组化合物所治疗的骨质疏松症，

9组化合物所治疗的类风湿关节炎，

10组化合物所治疗的伤口愈合。

下列实施例用于说明本发明，但实施例的选择并非是限制性的。 I.合成实施例 I.A前体 实施例1 (1-吡啶-2-基哌啶-4-基)甲胺(1) a.)将叔-丁基氧羰基-4-(氨基甲基)-1-哌啶(14g；65.33mmol；由 Prugh等，SyntheticCommunications22(16)，2361-2365(1992)) 中的方法制备)溶于50mlTHF中，在5℃下，加入6.6gN-甲基吗啉和 12.6g氯甲酸苄基酯，并搅拌混合物约2h。浓缩混合物，残余物用CH2Cl2吸收并用饱和NaCl溶液洗涤，干燥并过滤。浓缩后，剩余23.5g黄色油， 并将其从甲基叔丁基醚中结晶。 18g；ESI-MS[M+H+]＝293.15 b.)在0℃下，将25mlTFA加入含有叔-丁氧羰基-4-({[(苄基氧)羰基] 氨基}甲基)-1-哌啶1a(15g；43.05mmol)的125mlCH2Cl2溶液中，并 在10℃下，搅拌混合物20分钟，然后在室温下搅拌20分钟，浓缩混合 物并将所得残余物从二乙醚中结晶，得到14.5g游离胺作为TFA盐 (ESI-MS[M+H+]＝249.25；m.p.：109-110℃。将5gTFA盐和2.79g 乙基二异丙胺(DIPEA)加热在15ml2-氟吡啶中加热回流。反应完成后， 浓缩混合物，用乙酸乙酯吸收残余物，并用H2O和饱和NaCl溶液洗涤4 次。干燥，过滤，浓缩，得到4.49g淡褐色油，从正戊烷中结晶。 4.02g；ESI-MS[M+H+]＝362.15 c.)在标准条件下，用0.2gPd(10％在碳上)氢化含有3.9g1b的150ml CH3OH。将反应混合物经硅藻土过滤并浓缩，得到2.3g； ESI-MS[M+H+]＝192.15。 1H-NMR(270MHz；DMSO-d6)δ(ppm)8.1(m，1H)，7.5(m，1H)，6.8 (m，1H)，6.55(m，1H)，4.3(m，2H)，2.7(m2H)，2.45(m2H)， 1.75(m2H)，1.5(m1H)，1.05(m2H). 实施例2 N-(哌啶-4-基甲基)吡啶-2-胺(三氟乙酸盐)(2) a.)将叔丁氧羰基-4-(氨基甲基)-1-哌啶(3g；14mmol和10ml2- 氟吡啶回流4h。浓缩并在正戊烷中研制粗产物，得到3g白色固体， m.p.：126-130℃；ESI-MS[M+H+]＝292.15。 b.)将1gBoc保护的胺溶于5mlCH2Cl2中，并在0℃下加入10mlTFA 后，在室温下搅拌2h。蒸发反应混合物，得到1.9g淡黄色油，它可以 直接反应无需进一步提纯；ESI-MS[M+H+]＝192.15。 实施例3 N-[4-(氨基甲基)苄基]吡啶-2-胺(盐酸盐)(3) a.)将2-氨基吡啶(20g；212mmol)溶于100mlCH3OH中，用盐酸异丙 醇溶液将pH调至6，加入36.2g(276mmol)对氰基苯甲醛，然后在1 小时内将9.3g(148mmol)氰基硼氢化钠分批加入。将黄色悬浮液搅拌 过夜，然后浓缩。用100ml水吸收残余物，并用KOH将pH调至＞10。用NaCl饱和水相，并用二乙醚提取三次。将醚相过滤，滤液用FeSO4溶液洗涤三 次，干燥并浓缩。残余物层析得到40.55g；ESI-MS[M+H+]＝210.15。 b.)将10g腈3a引入280ml甲醇氨溶液，在加入10g甲醇洗涤的阮内镍 后，在室温下氢化28h。过滤和浓缩后所得的残余物，通过在硅胶上层析 提纯。将如此获得的主要级分溶于二乙醚，与盐酸异丙醇溶液混合，并 结晶过夜。用抽吸滤去所形成的沉淀物，用500ml异丙醇洗涤并煮沸。 将产物乘热抽吸滤去并干燥。11.2g；ESI-MS[M+H+]＝214.05 实施例4 [4-(1H-苯并咪唑2-基)-1，3-噻唑-2-基]甲胺(三氟乙酸盐)(4)

通过标准方法从2-(氨基甲基)-1，3-噻唑-4-腈制备用作前体的叔 丁基(4-氰基-1，3-噻唑-2-基)甲基氨基甲酸酯(WO98/067415) a.)将1.89g30％NaOCH3溶液加入含有叔丁基(4-氰基-1，3-噻唑-2- 基)甲基氨基甲酸酯(2.5g；10.45mmol)的25mlCHOH3中，并在室温 下搅拌混合物2h。加入1.9g1，2-苯二胺双盐酸盐后，搅拌过夜，然后 将反应混合物加入100mlH2O中，并过滤，并将如此获得的固体真空干燥。 3.0g；ESI-MS[M+H+]＝331.15 1H-NMR(400MHz；DMSO-d6)δ(ppm)8.25(s，1H)，7.95(m，1H)， 7.65(m，1H)，7.55(m，1H)，(m，1H)，7.2(m，2H)，4.55(m， 2H)，1.45(s，9H). b.)将1.0gBoc化合物4a溶于10mlCH2Cl2中，并且在0℃下加入10mlTFA 后，在室温下搅拌2h。蒸发反应混合物，并用正戊烷研制，得到1.5g作 为三氟乙酸盐的胺。Mp.：229-230℃；ESI-MS[M+H+]＝231.05 实施例5 [4-(1H-苯并咪唑2-基)-噻吩-2-基]甲胺(三氟乙酸盐)(5)

通过标准方法从5-(氨基甲基)-3-噻吩腈制备用作前体的叔丁基(4- 氰基噻吩-2-基)甲基氨基甲酸酯(WO98/06741) a.)将3.6g30％NaOCH3溶液加入含有叔丁基(4-氰基噻吩-2-基)甲基 氨基甲酸酯(5g；20.98mmol)的70mlCHOH3中，并在室温下搅拌混合 物2h。加入3.6g1，2-苯二胺双盐酸盐后，搅拌过夜，然后将反应混合 物加入50mlH2O中，并用CHCl2提取。干燥并浓缩有机相，得到4.3g黄 色固体，它可以通过在硅胶上层析(CH2Cl2/CH3OH1％→10％)提纯。1.6g； ESI-MS：[M+H+]＝333.15 b.)将1.5gBoc化合物5a溶于10mlCH2Cl2中，并且在0℃下加入15mlTFA 后，在室温下搅拌2h。蒸发反应混合物，并用正戊烷研制，得到1.5g作 为三氟乙酸盐的胺。 实施例6 [4-(1H-苯并咪唑-2-基)苯基]甲胺(三氟乙酸盐)(6) a.)将含有二(叔丁基)-4-氰基苄基亚氨基二碳酸酯(10g；30.08mmol； 按Lila等，Synth.Comm.28，23，1998，4419及以下页中的方法制备) 的200ml吡啶，与45ml三乙胺混合，在0℃下，用H2S饱和1.5h。反 应混合物在室温下静置过夜，然后蒸发。将用此方法获得的残余物用二 乙醚研制，用抽吸滤去并干燥(8.5g)。 b.)在室温下，用23.2gCH3I将40ml干燥CH2Cl2中的6g硫代酰胺6a(16.37 mmol)烷基化过夜，然后蒸发混合物。将用此方法获得的残余物吸收入40ml CH3OH中，加入1.95g1，2-苯二胺后，再搅拌过夜。蒸发反应混合物并 用正戊烷研制此固体，得到6.9g所需的苯并咪唑。Mp.：＞170℃(分解)； ESI-MS：[M+H+]＝424.25 c.)将3g双-Boc化合物6b溶于7mlCH2Cl2中，并且在0℃下加入20mlTFA 后，在室温下搅拌3h。蒸发反应混合物，并用正戊烷研制，得到3.2g胺 (三氟乙酸盐)； ESI-MS：[M+H+]＝224.05. 实施例7 [3-(1H-苯并咪唑2-基)苯基]甲胺(三氟乙酸盐)(7) a.)用与Lila等，Synth.Comm.28，23，1998，4419相似的方法，将 3-(氯甲基)苄腈(30g；197.9mmol)与二叔丁基亚氨基二羧酸酯 反应，以得到二(叔丁基)-3-(1H-苯并咪唑-2-基)苄基亚氨基二 碳酸酯。获得65g淡红色油，此油可以使用，无需进一步提纯。 b.)用16.5g，用6b中的相似方法，将其转化为硫代酰胺；并用正戊烷 将此粗产物研制，得到呈黄色固体的18.1g硫代酰胺。 c.)用6c中所述的条件相似的条件，进行烷基化和与1，2-苯二胺的反应； 从7.4g硫代酰胺开始，用正戊烷对粗产物进行研制，获得8.5g相应 的苯并咪唑。ESI-MS[M+H+]＝424.25 d.)将7.2g双-Boc化合物7c溶于20mlCH2Cl2中，并且在0℃下加入50ml TFA后，在室温下搅拌3h。蒸发反应混合物，并用甲基叔丁基醚研制， 得到3.2g胺(三氟乙酸盐)； ESI-MS[M+H+]＝224.15. 实施例8 N-[4-(氨基甲基)苯基]-N’-苄脲(三氟乙酸盐)(8) a.)在0℃下，将三乙胺(6.8g，67.12mmol)，然后将二-叔丁基二碳酸 酯(18.6g，85.00mmol)加入含有4-氨基苄胺(10.0g，81.85mmol) 的150mlCH2Cl2中。混合物在0℃下搅拌1h，然后在室温下搅拌2h。 为了处理，加入150ml1％柠檬酸水溶液，分离相，水相用CH2Cl2(150ml) 提取两次。再用水洗涤，用Na2SO4将混合的有机相干燥，并蒸发得到一 种固体，与少许二异丙醚一同搅拌，用抽吸滤去并干燥。13.0g；ESI-MS [M+H+-tBu]＝167.05 1H-NMR(360MHz，CDCl3)δ(ppm)：7.04(2H，d)，6.61(2H，d)， 4.78(1H，sbr.)，4.17(2H，d)，3.67(2H，sbr.)，1.46 (9H，s). b.)将异氰酸苄基酯(2.40g，18.00mmol)加入一种含有被护胺8a(4.0g， 17.99mmol)和三乙胺(1.82g，18.00mmol)的200ml甲苯/DMF10∶1 溶液。反应混合物在室温下搅拌过夜。可以将一部分所形成的脲直接作 为沉淀过滤并干燥。滤液用H2O、稀酒石酸洗涤两次至pH为3，用H2O再 洗涤两次至pH为5，然后干燥有机相并蒸发。用此方法共获得6.0g；ESI-MS [M+H+-tBu]＝300.15。 c.)将用此方法所获得的脲8b引入90mlCH2Cl2，并在0℃下，将TFA(2.24g； 196.25mmol)-溶于90mlCH2Cl2-滴入。3小时后，加入另外1mlTFA， 然后在室温下将混合物搅拌过夜。重复加入1mlTFA后，搅拌混合物5h， 然后倒入冰水中，并用乙酸乙酯(2×50ml)提取。用2NNaOH溶液将水 相调至碱性，并用CH2Cl2(2×50ml)提取。通过过滤去掉相之间的不溶 部分并干燥。 4g；ESI-MS[2M+H+]＝511.35 1H-NMR(200MHz，DMSO)δ(ppm)：8.52(1H，s)，7.39-7.07 (9H，m)，6.62(1H，t)，4.27(2H，d)，3.61(2H，s). 实施例9 N-{[5-(氨基甲基)噻吩-3-基]甲基}吡啶-2-胺(三氟乙酸盐)(9) a.)用NH3将含有叔丁基(4-氰基噻吩-2-基)甲基氨基甲酸酯(7g；29.4 mmol)的120ml乙醇溶液饱和，然后在标准条件在阮内镍(9g含水悬浮 液；用乙醇倾析)存在下氢化。将反应混合物过滤，蒸发并在硅胶上将 所得残余物层析(CH2Cl2/CH3OH加氨水)，得到4.4g呈淡黄色油的胺。 b.)将1.2胺9a(4.3mmol)、0.6g乙基二异丙胺和15g2-氟吡啶回流20h。 混合物蒸发后所得的残余物用CH2Cl2吸收，用0.1NHCl和饱和的NaCl溶液洗涤，干燥然后再蒸发。 1g；ESI-MS[M+H+]＝320.15。 c.)将0.9gBoc保护的胺9b溶于10mlCH2Cl2中，并在0℃下加入5mlTFA 后，在室温下搅拌1h。蒸发反应混合物，得到1.65g淡棕色油，它可以 直接反应无需进一步提纯(ESI-MS[M+H+]＝220.05)。 实施例10 2-[4-(1H-苯并咪唑-2-基)苯基]乙胺(三氟乙酸盐)(10) a.)在标准条件下，将7g4-(2-氨基乙基)苄腈转化为相应的Boc衍生 物。研制所得的粗产物，得到7.3g白色固体；(ESI-MS[M+H+]＝247.15) b.)用与6b中的相似方法，将4gBoc衍生物10a转化为硫代酰胺。并 用正戊烷将此粗产物研制，得到4.2g淡黄色固体，然后用与6b的相似 方法，将此固体烷基化并与1，2-苯二胺反应，得到苯并咪唑。如此获得 的粗产物通过在硅胶上层析(CH2Cl2/CH3OH4％→50％)提纯。 4.8g；ESI-MS[M+H+]＝338.15 c.)将4.8gBoc保护的胺10b溶于15mlCH2Cl2中，并且在0℃下加入30ml TFA后，在室温下搅拌3h。蒸发反应混合物，并用正戊烷研制，得到7.3g 固体。 ESI-MS[M+H+]＝238.05 1H-NMR(400MHz，DMSO)δ(ppm)：8.30(m，2H，8.0(sbr，3H)， 7.85，7.7和7.55(jem，2H)，3.18(m，2H)，3.05(m，2H). 实施例11 N1-吡啶-2-基乙烷-1，2-二胺(11)

用与Nicolaou等；Bioorg.Med.Chem.6(1998)，1185-1208的相 似方法制备；从100g2-溴吡啶开始，粗产物蒸馏，得到48.4g。 实施例12 N1-吡啶-2-基丙烷-1，3-二胺(12)

将2-溴吡啶(100g；0.633mol)和1，3-二氨基丙烷(234.5g；3.16mol) 回流7h。反应完成后，蒸发混合物。在真空油泵下蒸馏剩余的残余物， 得到43g所需产物。 1H-NMR(360MHz，CDCl3)δ(ppm)：8.05(d，1H)，7.36(t，1H)，6.51 (t，1H)，6.36(d，1H)，4.98(s，1H)，3.35(s，2H)，2.82(t，2H)， 1.73(m，1H)，1.32(s，2H). 实施例13 N1-甲基-N2-吡啶-2-基乙烷-1，2-二胺(乙酸盐)(13) a.)将2-氨基乙基(甲基)氨基甲酸叔丁酯(2.8g；16.1mmol)和19ml2- 氟吡啶回流约23h。蒸发反应混合物，得到4g褐色油(ESI-MS[M+H+]＝ 252.15)，它可以直接进一步反应。 b.)将2g13a的粗产物在30mlTFA中搅拌过夜。蒸发混合物并在RP硅 胶上通过MPLC提纯(CH3CN/H2O加0.1％乙酸)。 2.2g；ESI-MS[M+H+]＝152.1 实施例14 4-(氨基甲基)-N-苄基哌啶-1-甲酰胺 a.)将哌啶-4-甲基氨基甲酸苄酯(三氟乙酸盐)(4g；11.04mmol； 如对2所述制备)悬浮于60ml甲苯中并与1.43g乙基二异丙胺和异氰酸 苄基酯(1.62g；12.14mmol)回流4小时。蒸发反应混合物后的残余物 用CH2Cl2吸收并用1NHCl和饱和NaCl溶液提取两次，并将有机相干燥 并浓缩。4.2g；ESI-MS[M+H+]＝382.25 b.)在加热下，将4g苄脲14a溶于乙酸乙酯/CH3OH3∶1的昆合物中， 并且在加入0.2g10％Pd/活性炭后，在35-40℃标准条件下氢化。反应 完成后，混合物通过硅藻土过滤并蒸发。 2.8g；ESI-MS[M+H+]＝248.15 1H-NMR(400MHz，DMSO)δppm：7.4-7.15(m，11H)，7.05(t，1H)， 5.08(s，2H)，4.25(d，2H)，3.95(d，2H)，2.8和2.65 (jem，2H)，1.6(m，3H)，0.95(m，2H). 实施例15 (5，6-二甲基-1H-苯并咪唑-2-基)甲基氨基甲酸叔丁酯(15)

将1.3g30％NaOCH3溶液加入含有氰基甲基氨基甲酸叔丁酯(0.4g；25.6 mmol)的10mlCH3OH中，并在室温下搅拌混合物1h。加入5.15g4，5- 二氨基-邻-二甲苯双盐酸盐后，将反应混合物搅拌过夜，然后加入100ml H2O中，将通过过滤获得的固体在30℃下真空干燥。 0.5g；ESI-MS[M+H+]＝276

通过(在标准条件下)用TFA去除Boc基团，获得下面反应所需的胺； 然后将分离的TFA盐直接用于相应的偶合反应。 实施例16 [6-(1H-苯并咪唑-2-基)吡啶-3-基]甲胺(16) a.)用与1的相似方法从(6-氰基吡啶-3-基)甲基氨甲酸叔丁酯(6.0g， 25.72mmol)开始制备；从乙醇中结晶粗产物，得到5.15g；ESI-MS[M+H+] ＝325 b.)将含有0.55gBoc保护的胺16a的10mlCH2Cl2，与5mlTFA混合， 并在室温下搅拌2h。蒸发反应混合物，得到0.95g白色固体；ESI-MS[M+H+] ＝225.25 实施例17 3-氨基-N-(1H-咪唑-2-基)丙酰胺(17) a.)Z-β-丙氨酸(10g，44.8mmol)溶于200mlDMF中，并加入15.86g (3.5当量)的N-甲基吗啉和5.9g(0.5当量)的2-氨基咪唑硫酸盐。 在-10℃下，加入7.87g(1.3当量)的HOBt和的11.16g(1.3当量)的 EDC，并在加热至室温的同时将混合物搅拌1h，然后搅拌18h。加入150ml 乙醚，于是沉淀出一种白色固体，并用抽吸将其滤去。用冷乙醚洗涤残 余物并悬浮于乙酸乙酯中，并加入1NHCl直至反应为酸性。用乙酸乙酯 提取水溶液一次，然后在4℃下，用10％NaOH将水相调至pH为碱性。 用抽吸滤去所得沉淀物并用水洗涤。 5.4g；ESI-MS[M+H+]＝289.05 b.)将5.3gZ化合物17a悬浮于250ml乙醇中，并加入530mg10％在 活性碳上的钯。用H2在室温下进行氢化18h，然后用CH3OH稀释后，将悬 浮液煮沸，于是产物沉淀溶解。过滤并浓缩溶液，得到1.5g。 ESI-MS[M+H+]＝155.05 实施例18 4-(氨基甲基)苄基氨甲酸叔丁酯(18)

在0℃下，将24g(111mmol)的二叔丁基碳酸酯滴入含有4-(氨基 甲基)苄胺(50.7g；372mmol)1000MCH2Cl2中。在室温下搅拌混合物 21h。然后用CH2Cl2稀释，并用5％Na2CO3溶液洗涤，将CH2Cl2相干燥并 浓缩。将残余物溶于1NHCl中，并用二乙醚提取两次。用50％NaOH将 水相的pH调至10，并用乙酸乙酯提取。将有机相混合、干燥并浓缩。 1.48g；ESI-MS[2M+H+]＝473.25 实施例19 N1-吡啶-2-基环己烷-1，2-二胺(19)

将2-溴吡啶(20g；127.6mmol)和72.3g(633mmol)的1，2-二 氨基环己烷与15ml吡啶混合，并在120℃下，总共搅拌5×8h并在室温 下搅拌2周。在寒冷中变成固体的残余物与正庚烷一起搅拌，用抽吸滤 去固体并分离。浓缩母液，用水吸收残余物，并用HCl将pH调至8至9。 用CH2Cl2提取溶液，并用水洗涤有机相并浓缩。剩余的油缓慢地结晶， 然后与戊烷一同搅拌，用抽吸滤去，并再用甲基叔丁基醚研制，并用抽 吸滤去。所得的产物(4.9g)由85％反式化合物和15％顺式化合物组成。 13C-NMR(400MHz，CDCl3)，δ(ppm)＝159.09(Py-C-2/反式)，158.46 (Py-C-2/顺式)，58.19，56.16，35.03，32.74，25.28，25.03( 环已烷环/反式)，52.28，49.78，32.29，27.75(环己烷环/顺式). 实施例20 N-[4-(氨基甲基)-1，3-噻唑-2-基]-N’-苄脲(盐酸盐)(20) a.)将一种含有123g吡啶鎓溴化物过溴化物的600mlTHF缓慢地滴入含 有2-(2-氧代丙基)-1H-异吲哚-1，3(2H)-二酮(70g；0.345mol) 的600mlTHF中，然后将混合物搅拌大约3h。为了处理，滤去沉淀的固 体，浓缩母液，残余物用乙酸乙酯吸收，并将溶液用亚硫酸氢盐水溶液 充分洗涤。干燥并浓缩，得到150g黄色油，它是经甲基叔丁基醚研制的。 63.4g；m.p.：142-143℃；ESI-MS[M+H+]＝283.95 b.)在室温下，在70mlTHF中搅拌2-(3-溴-2-氧代丙基)-1H-异吲哚- 1，3(2H)-二酮20a(6g；21.27mmol)和硫脲(2g；26.27mmol)大约 2h。用抽吸滤去沉淀物并干燥。 5g；ESI-MS[M+H+]＝260.05 c.)将2-[(2-氨基1，3-噻唑-4-基)甲基-1H-异吲哚-1，3(2H)-二酮 氢溴酸盐20b(4.5g；13.23mmol)、异氰酸苄基酯(1.8g；13.52mmol) 和1.7g乙基二异丙胺在50ml甲苯中回流。反应完成后，浓缩混合物， 将残余物吸收入CH2Cl2中，并用1NHCl、饱和NaHCO3和NaCl溶液洗涤。 干燥并浓缩，得到4.7g桔黄色固体，它是从CH3OH中重结晶的。 3.0g；ESI-MS[M+H+]＝393.05 1H-NMR(360MHz，DMSO)δppm：10.65(s，1H)，7.9(m，4H)，7.25 (m，5H)，6.85(s，1H)，4.7(s，2H)，4.35(d，2H)， d.)将N-苄基-N’-{4-[(1，3-二氧代-1，3-二氢-2H-异吲哚-2-基)-甲 基]-1，3-噻唑-2-基}脲20c(3g；7.64mmol)悬浮于50mlCH3OH中， 然后在加入2g水合肼后，在室温下搅拌2h。滤去所得固体，并将所得母 液蒸发并用0.5NHCl研制。重新过滤和浓缩母液，以富集所需产物，并 因此将此提纯步骤重复三次。 0.78g；ESI-MS[M+H+]＝263.05 实施例21 N-(哌啶-4-基甲基)-1H-苯并咪唑-2-胺(三氟乙酸盐)(21) a.)在0℃下，将一种含有叔丁氧基羰基-4-(氨基甲基)-1-哌啶(5.39g； 25mmol)的25mlCH3CN滴入含有6.75g硫代羰基二咪唑和0.5g咪唑的 100mlCH3CN中，然后在室温下将混合物搅拌3h。然后，加入1，2-苯二 胺(5.5g；50.86mmol)，并在60℃下加热混合物大约1h。用抽吸滤去冷 却所获得的固体并干燥。 6.79g；ESI-MS[M+H+-tBu]＝309.15 b.)将含有4-({[(2-氨基苯胺基)硫代羰基]氨基}甲基)-哌啶-1-甲酸叔 丁酯21a(5g；13.72mmol)、5.94gHgO(黄色)和0.6g硫的150ml乙 醇溶液回流1h。混合物通过硅藻土过滤两次并蒸发，通过在硅胶上层析 (CH2Cl2/CH3OH5％→25％)将所得的粗产物提纯。 2.65g；ESI-MS[M+H+]＝331.25 1H-NMR(360MHz，DMSO)δppm：7.15和6.9(jem，2H)， 3.95(d，2H)，3.2(m2H)，2.7(brm；2H)，1.8(m，1H)， 1.7(m，2H)，1.35(s，9H)，1.05(m，2H). c.)在标准条件下，用10mlTFA处理4-[(1H-苯并咪唑-2-基氨基)甲基] 哌啶-1-甲酸叔丁酯21b(2.65g；8.02mmol)。浓缩并用正戊烷将粗产 物研制，得到2.3g； ESI-MS[M+H+]＝231.15 1H-NR(360MHz，DMSO)δppm：13.25(s，1H)，9.35(m，1H)， 8.8und8.5(jebrs，1H)，7.4和7.20(jem，2H)， 3.3(m，4H)，2.85(m，2H)，1.9(m，3H)，1.35(m，2H). 实施例22 a)2-(N-乙酯基硫代氨基甲酰)-1-(N-哌啶子基)-1-丙烯(22a)

在0℃下，将40ml哌啶滴入11.85g(0.2mol)的丙醛和10g的K2CO3中。然后在此温度下搅拌混合物2h，并滤去不溶解的部分，并将滤液在 真空下分馏。在冷却的情况下，将N-乙氧羰基异硫氰酸酯(63.7g； 0.48mol)滴入含有刚刚蒸馏的1-(N-哌啶子基)丙烯(9.58g；0.077mol) 的40ml无水二乙醚的溶液中；在加入过程中，有桔红色沉淀物形成。在 0至5℃下，将反应混合物进一步搅拌大约4h，并滤去沉淀，洗涤并干燥。 用二乙醚再次处理蒸发母液后所剩余的残余物并过滤。 产率：6.81g 1H-NMR(400MHz，CDCl3)：δ(ppm)7.85(s，1H；CH＝C)， 7.70(br，1H，NH)，4.15(q，2H，CH2)，3.6(m，4H，哌啶)， 2.2(s，3H，CH3)，1.7(m，6H，哌啶)，1.3(t，3H，CH3). b)2-(N-乙酯基硫代氨基甲酰)-1-(N-哌啶子基)-2-苯乙烯(22b)

将15.8ml(0.1mol)的浓度为50％的苯乙醛的邻苯二甲酸二乙酯溶液， 与5gK2CO3，在0℃下混合，并且在此温度下，缓慢加入17.04g＝19.8ml (0.2mol)的哌啶。在0至5℃下，将反应混合物搅拌1.5h。然后用抽 吸将不溶部分滤去，并将母液在浴温度至80℃、真空油泵下蒸馏。在0 ℃、氮气下，将作为残余物的所得黄色油(27.15g，含有大约50％邻苯 二甲酸二乙酯)引入40ml无水二乙醚中。在0℃下，缓慢注入8.1ml＝ 9.02g(80mmol)的N-乙氧基羰基异硫氰酸酯。然后，在0至5℃下， 将混合物搅拌4h，大约30分钟后，沉淀出桔黄色固体。在N2下，用抽 吸滤去固体，用二乙醚洗涤，并在N2气流下干燥。 产率：21.5g黄色固体 1H-NMR(400MHz，CDCl3)：δ(ppm)8.45(s，1H；CH＝C)，7.65 (br，1H，NH)，7.35(m，5H，苯基)，4.1(q，2H，CH2)，3.1 (m，4H，哌啶)，1.5(m，6H，哌啶)，1.15(t，3H， CH3). 下列用与22a的相似方法制备： c)4，4-二甲基-2-(N-乙酯基硫代氨基甲酰)-1-(N-哌啶子基)-1-戊 烯(22c)

将从24.03g(0.2mol)的4，4-二甲基戊醛、10gk2CO3和39.6ml 哌啶中获得的烯胺，与7.68ml(65.1mmol)的N-乙氧基羰基异硫氰 酸酯反应。 产率：黄色固体8.86g。 1H-NMR(270MHz，CDCl3)：δ(ppm)7.95(br，1H，NH)，7.52 (s，1H；CH＝C)，4.17(q，2H，CH2)，3.46(m，4H，哌啶)， 2.83(s，2H，CH2)，1.66(m，6H，哌啶)，1.28(t，3H，CH3)， 0.95(s，9H，3*CH3). d)2-(N-乙酯基硫代氨基甲酰)-1-(N-哌啶子基)-1-戊烯(22d)

将从17.23g(0.2mol)的戊醛、10gk2CO3和39.6ml哌啶中获得的 烯胺，与8.84ml(74.9mmol)的N-乙氧基羰基异硫氰酸酯反应。 产率：深黄色固体15.15g。 1H-NMR(270MHz，CDCl3)：δ(ppm)7.77(br，1H，NH)，7.52 (s，1H；CH＝C)，4.15(q，2H，CH2)，3.5(m，4H，哌啶)，2.7 (t，2H，CH2)，1.7(m，6H，哌啶)，1.55(m，2H，CH2)，1.3 (t，3H，CH3)，0.95(t，3H，CH3). e)2-(N-乙酯基硫代氨基甲酰)-2-(四氢-2H-吡喃-4-基)-1-(N-哌啶 子基)乙烯(22e)

将从25.84g(0.2mol)的4-甲酰基甲基四氢吡喃、10gk2CO3和39.6 ml哌啶中获得的烯胺，与10.1ml(85.6mmol)的N-乙氧基羰基异硫氰 酸酯反应。 产率：黄色固体27g。 1H-NMR(270MHz，CDCl3)：δ(ppm)8.2(br，1H，NH)，6.84 (s，1H；CH＝C)，4.15(q，2H，CH2)，3.95和3.5(分别m， 2H，THP-OCH2)，3.2(m，4H，哌啶-NCH2)，2.65(m，1H，THP-CH)，1.65-1.95(m，10H，哌啶-CH2和THP-CH2)，1.3 (t，3H，CH3). 实施例23 2-(哌啶-4-基氨基)吡啶(23) a)将4-氨基-1-哌啶羧酸乙基酯(6g；34.8mmol)和25g的2-氟吡啶 回流48h。用抽吸滤去冷却后所形成的固体，用正戊烷研制并干燥；6.26g 黄色粉末；ESI-MS[M+H+]＝250.15。 b)将6g4-(吡啶-2-基氨基)哌啶-1-羧酸乙基酯(23a)在30ml47％HBr中回流6h。蒸发混合物，用乙酸乙酯/CH3OH(9∶1)研制所得的粗产物 并重新干燥，得到7.1g白色固体；ESI-MS[M+H+]＝178.15。 实施例24 N-[4-(氨基甲基)-苯基]-1H-苯并咪唑-2-胺(三氟乙酸盐)(24) a)用与21a的相似方法，将4-氨基苄基氨甲酸叔丁基酯(5g；22.5mmol) 与6g硫代羰基二咪唑、0.3g咪唑和4.86g1，2-苯二胺反应。用此方法 获得的粗产物，通过在硅胶上层析(CH2Cl2/CH3OH2→10％)提纯。8.2g油； ESI-MS[M+H+]＝373.15 1H-NMR(360MHz，DMSO)δppm：9.5和9.05(jes，1H)，7.45 (d，2H)，7.35(m，1H)，7.20(d，1H)，7.15，6.95，6.75，6.60 (jem，1H)，4.85(s，2H)，4.10(d，2H)，1.35(s，9H). b)用与21c相似的方法，将4-{[(2-氨基苯胺基)硫代羰基]氨基}苄基-氨 甲酸叔丁基酯(4.3g；11.54mmol)、5gHgO(黄色)和0.05g硫在150ml 乙醇中回流。通过硅藻土将反应混合物过滤并浓缩，得到2.1g深色固体 (ESI-MS[M+H+]＝339.15)。无需进一步纯化，在室温下，用15mlTFA 处理从此方法中获得的4-(1H-苯并咪唑-2-基氨基)苄基-氨甲酸叔丁基 酯2h，并浓缩，得到4.7g深色油，它可以进一步反应，无需进一步提纯 (ESI-MS[M+H+]＝239.05)。 1H-NMR(360MHz，DMSO)δppm：11.25(s，1H)，8.25(s宽， 2-3H)，7.60(m，4H)，7.40(m，2H)，7.30(m2H)，4.15(m，2H). 实施例25 [5-(1-苯并咪唑-2-基)噻吩-2-基]甲胺(25) a)将5-(氨基甲基)噻吩-2-腈(25g；146mmol)(如WO95/23609中所 述制备)溶于750mlCH2Cl2中，并加入50ml乙基二异丙胺。在冰中冷却 的同时，将二叔丁基二碳酸酯(35.05g；160mmol)加入此溶液中。16h 后，用10％柠檬酸洗涤4次，用饱和NaHCO3溶液洗涤2次，用饱和NaCl溶液洗涤1次。干燥有机相并浓缩。(38.2g) b)将(5-氰基噻吩-2基)甲基氨甲酸叔丁基酯(25g)溶于甲醇中，并加 入19.3ml浓度为30％的甲醇钠的甲醇溶液。16h后，再加入1.9ml甲醇 钠溶液，并将混合物加热至40-50℃。2h后，将混合物冷却至室温并加 入1，2-苯二胺盐酸盐。3天后，冷却悬浮液并与250ml水混合，并用抽 吸滤去沉淀。固体用水洗涤并干燥(19.6g)。将9.5g的此沉淀悬浮于400ml CH2Cl2中，并在室温下，加入22mlTFA。16h后，浓缩混合物，将残余物 溶于水并用二乙醚提取2次，并将水相的pH调至10-11，然后用乙酸乙 酯提取2次。水相用NaCl饱和并用乙酸乙酯再次提取。干燥混合的有机 相并浓缩。 6.3g；ESI-MS[M+H+]＝230.1 实施例26 3-[(5，6-二甲基-1H-苯并咪唑-2-基)氨基]-3-氧代丙-1-胺(盐酸盐) (26)

Boc-β-丙氨酸(1.89g；10mmol)溶于15mlDMF中，在加入2.02gN- 甲基吗啉、0.122g二甲基氨基吡啶和1.92gEDC*HCl后，搅拌1h。向 澄清溶液中加入1.93g(12mmol)的2-氨基-5，6-二甲基苯并咪唑，并 在室温下搅拌16h，然后在60℃下搅拌1h。反应完成后，加入NaCl溶液， 然后用乙酸乙酯提取2次，有机相用10％柠檬酸洗涤2次并用水洗涤2 次，干燥并浓缩。将残余物(1.3g)溶于10mlCH2Cl2中，并加入10mlTFA。 2h后，蒸发混合物，用二乙醚吸收残余物，加入HCl乙醚溶液。1h后， 用抽吸滤去结晶，洗涤至中性并在40℃下干燥。 0.90g；ESI-MS[M+H+]＝233.2 1H-NMR(270MHz，DMSO-d6)δppm＝8.3(bs，3H)，7.45(s，2H)， 3.25-3.0(m，4H)，2.35(s，6H). 实施例27 3-[(1H-苯并咪唑-2-基)氨基]-3-氧代丙-1-胺(盐酸盐)(27)

用与26相似的制备方法，从(1.60g；12mmol)的2-氨基苯并咪唑开 始合成。 1H-NMR(270MHz；DMSO-d6)δppm：8.3(bs，3H)，7.7(m，2H)，7.4(m， 2H)，3.15(m，2H)，3.10(m，2H). 实施例28 2-[(哌啶鎓-4-基羰基)氨基]-1H-苯并咪唑(双三氟乙酸盐)(28)

将含有Boc-异3-哌啶甲酸(3.0g；13.08mmol)的10mlCH2Cl2与13.4ml 乙基二异丙胺和1.74g(13.08mmol)2-氨基吡啶混合。在冷却至4℃后， 滴入15.4ml50％的丙烷膦酸酐溶液，并将混合物搅拌1.5h。然后在室 温下，搅拌混合物4h，然后浓缩并用乙酸乙酯吸收。溶液用稀NaOH、水 和10％浓度的柠檬酸提取并用饱和的NaCl溶液提取3次。干燥并浓缩有 机相，残余物从二乙醚(1.30g)中结晶。将1.25g沉淀溶于15mlCH2Cl2中，并加入15mlTFA。3h后，浓缩混合物并将残余物从二乙醚中结晶。 冷却至0℃后，用抽吸滤去残余物并干燥。 1.20g；ESI-MS[M+H+]＝245.2 实施例29 N-吡啶-2-基哌啶-4-甲酰胺(双三氟乙酸盐)(29)

用与28的相似方法，从1.23g(13.08mmol)的2-氨基吡啶开始制备。 所得产物是吸湿性的，通过与甲苯共馏干燥。 0.72g；ESI-MS[M+H+]＝206.2 实施例30 N-[4-(氨基甲基)-1，3-噻唑-2-基]吡啶-2-胺(盐酸盐)(30) a)2-氨基吡啶(11g；116.9mmol)和异硫氰酸苄基酯(21g；128.7mmol) 在250ml丙酮中回流3h。蒸发混合物并将所得残余物首先用丙酮/正戊 烷，然后只用正戊烷研制。 21.4g；ESI-MS[M+H+]＝258.05 b)将N-苯甲酰基-N’-吡啶-2-基硫脲(30a)(5g；19.43mmol)引入100ml 丙酮/CH3OH混合物中，并在加入含有1.34gK2CO3的5mlH2O后，回流2h。 为了处理，滤去所形成的沉淀，蒸发母液，并将所得残余物加入H2O中。 用CH2Cl2提取、干燥和蒸发有机相，得到5.4g； ESI-MS[M+H+]＝154.05 1H-NMR(270MHz，DMSO-d6)δppm：10.65(s，1H)，10.55(s，1H)， 8.9(s，1H)，8.25，7.75，7.20，7.10(jem，1H). c)在室温下，将N-吡啶-2-基硫脲(30b)(5g；35.9mmol)和2-(3-溴- 2-氧代丙基)-1H-异吲哚-1，3-(2H)-二酮在500mlTHF中搅拌2h。 滤去所形成的沉淀并干燥。 12.3g白色固体；ESI-MS[M+H+]＝337.05。 d)用与20d的相似方法，从2-{[2-(吡啶-2-基氨基)-1，3-噻唑-4-基]- 甲基}-1H-异吲哚-1，3(2H)-二酮(30c)(10g；23.96mmol)和含有7g 水合肼的250mlCH3OH开始，去除邻苯二甲酰基团。随后处理，得到4.15g 黄色固体；ESI-MS[M+H+]＝207.05。 实施例31 4-[(1，4，5，6-四氢嘧啶-2-基氨基)甲基]哌啶(三氟乙酸盐)(31)

在室温下，将叔丁氧羰基-4-(氨基甲基)-1-哌啶(2g；9.33mmol)、 2-(甲基硫基)1，4，5，6-四氢嘧啶-1-鎓碘化物(2.41g；9.33mmol) 和1.2g乙基二异丙胺，在10mlDMF中搅拌24h。蒸发混合物，加入甲苯 /丙酮，滤去所得固体，并将滤液再次蒸发。获得褐色油作为粗产物(ESI-MS [M+H+]＝297.25)，它可以直接用10mlTFA处理，无需进一步提纯。蒸 发反应混合物，得到深褐色油，它可以通过MPLC(硅胶：Bischoff Prontoprep60-2540-C18E，32mm；洗脱液：CH3CN/H2O+0.1％乙酸)提 纯(1.36g油) 实施例32 [4-(吡啶-2-基氨基)苯基]甲胺(盐酸盐)(32)

将4-氨基苄基氨基甲酸叔丁基酯(4g；17.99mmol)和17.5g2-氟吡 啶回流32h。反应完成后，蒸发混合物，并将残余物用正戊烷研制。将此 方法所获得的粗产物(5.3g)溶于100mlCH2Cl2中，并在0℃下，加入6.9ml TFA。3.5h后，蒸发混合物，残余物用二乙醚吸收，并加入HCl乙醚溶液。 用抽吸滤去并干燥沉淀，得到3.3g相应的盐酸盐。 M.p.：208℃(分解)；ESI-MS[M+H+]＝200.15。 I.B.通式I的化合物 实施例I-1 乙酸4-({[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧乙基)-5-甲基-2-氧 代-1，2-二氢嘧啶-4-基]氨基}甲基)-1-吡啶-2-基哌啶鎓(I-1) a)用DMF中的哌啶(50％)，将1.5gZ-Dap(Fmoc)-2-Cl-三苯甲基树 脂(0.6mmol；取代0.4mmol/g树脂)处理20分钟。用DMF洗涤(5*1分 钟)后，将树脂悬浮于6mlDMF中，并在加入430mg2-(N-乙酯基硫代 氨基甲酰)-1-(N-哌啶子基)-3-丙烯(22a)后，在室温下恒温过夜。 然后，用DMF、MeOH、CH2Cl2和NMP洗涤。在4.5mlNMP中的树脂的悬浮 液与含有1.83gCs2CO3的0.89ml的H2O和0.56ml的5MBrCN的CH3CN溶液混合。在室温下恒温6h，然后用抽吸过滤并用NMP和CH2Cl2洗涤。 b)将用此方法获得的0.037mmol的树脂悬浮于3.5mlNMP中，并在加入 27μlDIPEA后，与14.2mg(1-吡啶-2-基哌啶-4-基)甲胺混合。恒温 过夜后，用抽吸过滤并用DMF、H2O、DMF、CH2Cl2、MeOH和CH2Cl2洗涤。 用1.5ml三氟乙醇/冰醋酸/CH2Cl2(1h，室温)，使产物从树脂解离。过 滤后蒸发，用2ml冰醋酸吸收并冷冻干燥。 产率：22mg ESI-MS[M+H+]：521(计算值：521)。 实施例I-2 乙酸2-{4-[1-(2-{[(苄氧基)羰基]氨基}-2-羧乙基)-2-氧代-5-四氢- 2H-吡喃-4-基-1，2-二氢嘧啶-4-基]哌嗪-1基}吡啶鎓(I-2)

将55mgZ-Dap-2-Cl-三苯甲基树脂(0.04mmol)悬浮于2mlDMF 中，并加入3当量的22e。恒温过夜后，用DMF、MeOH、CH2Cl2和NMP洗 涤。然后将树脂悬浮于NMP中，并加入含有131mgCs2CO3的63μl的H2O和40μl的5MBrCN的CH3CN溶液。在室温下恒温6h，然后用抽吸过滤 并用NMP和CH2Cl2洗涤。将所得树脂悬浮于3.5mlNMP中，并在加入28μl DIPEA后，与13.1mg1-(2-吡啶基)哌嗪混合。恒温过夜后，用抽吸过 滤并用DMF、H2O、DMF、CH2Cl2、MeOH和CH2Cl2洗涤。用1.5ml三氟乙 醇/冰醋酸/CH2Cl2(1h，室温)，使产物从树脂解离。过滤后蒸发，用2ml 冰醋酸吸收并冷冻干燥。 产率：24mg ESI-MS[M+H+]：563(计算值：563)。 实施例I-3 3-(4-[4-(苯胺基羰基)哌嗪-1-基]-5-甲基-2-氧代嘧啶-1(2H)-基)-N- [(苄基氧基)羰基]丙氨酸(I-3) a)将0.28mmol实施例I-1a)中所获得的树脂加入含有192.6μl (1.12mmol)DIPEA和2.4g哌嗪(哌嗪没有完全溶解，滤去不溶部分) 的15ml的NMP溶液。恒温过夜后，用抽吸过滤并用DMF、H2O、DMF、CH2Cl2、 MeOH和CH2Cl2洗涤。 b)将0.04mmol用此方法获得的树脂悬浮于CH2Cl2中，并在加入0.08mmol 异氰酸苯基酯后，在室温下恒温过夜。用1.5ml三氟乙醇/冰醋酸/CH2Cl2(1h，室温)，使产物从树脂解离。过滤后蒸发，用2ml冰醋酸吸收并冷 冻干燥。 产率：11mg ESI-MS[M+H+]：535(计算值：535)。 实施例I-4 三氟乙酸2-{[(1-{1-[2-羧基-1-(4-甲基苯基)乙基]-5-甲基-2-氧代- 1，2-二氢嘧啶-4-基}哌啶-4-基)甲基]氨基}吡啶鎓(I-4)

用与实施例I-1a)的相似方法，使0.037mmol的D，L-3-氨基-3-(4- 甲基苯基)丙酸-2-Cl-三苯甲基树脂发生反应，并然后悬浮于3.5ml 的NMP中。加入68μlDIPEA和21.7mg的N-(哌啶-4-基甲基)吡啶-2- 胺(三氟乙酸盐)，然后在室温下恒温过夜。用抽吸过滤后并用DMF、H2O、 DMF、CH2Cl2、MeOH和CH2Cl2洗涤。用1.5ml三氟乙醇/冰醋酸/CH2Cl2(1h， 室温)，使产物从树脂解离。过滤后蒸发，用2ml冰醋酸吸收并冷冻干燥。 通过RP-HPLC将粗产物提纯。 产率：5mg ESI-MS[M+H+]：462(计算值：462)。 实施例I-5 乙酸2-[(2-{[1-(4-羧基丁基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基] 氨基}乙基)氨基]吡啶鎓(I-5)

用与实施例I-1a)的相似方法，使0.04mmol的5-氨基戊酸-2-Cl-三苯 甲基树脂发生反应，向所得树脂的3.5ml的NMP的悬浮液中，加入28μl DIPEA和11mg的N1-吡啶-2基乙烷-1，2-二胺。在室温下恒温过夜，然 后用抽吸过滤并用DMF、H2O、DMF、CH2Cl2、MeOH和CH2Cl2洗涤。用1.5ml 三氟乙醇/冰醋酸/CH2Cl2(1h，室温)，使产物从树脂解离。过滤后蒸发， 用2ml冰醋酸吸收并冷冻干燥。 产率：16mg ESI-MS[M+H+]：346(计算值：346)。 类似地制备下列化合物： 实施例 I-6乙酸2-{4-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基-乙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-哌嗪-1-基}-6-甲基吡啶鎓 ESI-MS[M+H]+：507(计算值：507) I-7乙酸2-{4-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基-乙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-哌嗪-1-基}吡啶鎓 ESI-MS[M+H]+：493(计算值：493) I-8乙酸2-{4-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基-乙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-哌嗪-1-基}吡啶鎓 ESI-MS[M+H]+：493(计算值：493) I-9二乙酸1-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基-乙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-4-吡嗪-4-鎓-2-基哌嗪-4-鎓 ESI-MS[M+H]+：494(计算值：494) I-10二乙酸1-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-5-甲

基-2-氧代-1，2-二氢嘧啶-4-基]-4-(吡啶鎓-4-基甲基)哌嗪-4-

鎓 ESI-MS[M+H]+：507(计算值：507) I-11二乙酸4-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-5-甲

基-2-氧代-1，2-二氢嘧啶4-基]-1-(3-吡咯烷鎓-1-基丙基)-

1，4-diazepan-1-鎓 ESI-MS[M+H]+：541(计算值：541) I-123-(4-{4-[(苄氨基)羰基]哌嗪-1-基}-5-甲基-2-氧代嘧啶-

1(2H)-基)-N-[(苄氧基)羰基)丙氨酸 ESI-MS[M+H]+：549(计算值：549) I-13乙酸2-[(2-{[1-((2S)2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}乙基)氨基]吡啶鎓 ESI-MS[M+H]+：467(计算值：467) I-14乙酸2-[(2-{[1-(4-{[(苄氧基)羰基]氨基}-4-羧基-丁基)-5-甲

基-2-氧代-1，2-二氢嘧啶-4-基]-氨基}乙基)氨基]吡啶鎓 ESI-MS[M+H]+：495(计算值：495) I-15乙酸2-[(2-{[1-(5-{[(苄氧基)羰基]氨基}-5-羧基-戊基)-5-甲

基-2-氧代-1，2-二氢嘧啶-4-基]-氨基}乙基)氨基]吡啶鎓 ESI-MS[M+H]+：509(计算值：509) I-16乙酸2-{4-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基-乙基)-2-

氧代-5-苯基-1，2-二氢嘧啶-4-基]-哌嗪-1-基}吡啶鎓 ESI-MS[M+H]+：555(计算值：555) I-17乙酸2-{4-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基-乙基)-5-

新戊基-2-氧代-1，2-二氢嘧啶-4-基]-哌嗪-1-基}吡啶鎓 ESI-MS[M+H]+：549(计算值：549) I-18乙酸2-{4-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基-乙基)-2-

氧代-5-丙基-1，2-二氢嘧啶-4-基]-哌嗪-1-基}吡啶鎓 ESI-MS[M+H]+：521(计算值：521) I-193-(4-[4-(苯胺羰基)-1，4-diazepan-1-基]-5-甲基-2-氧代嘧啶-

1(2H)-基)-N-[(苄氧基)羰基]丙氨酸 ESI-MS[M+H]+：549(计算值：549) I-20乙酸2-{4-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-甲基-

2-氧代-1，2-二氢嘧啶-4-基]哌嗪-1-基}吡啶鎓 ESI-MS[M+H]+：507(计算值：507) I-21乙酸2-{4-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-2-氧代-

5-苯基-1，2-二氢嘧啶-4-基]哌嗪-1-基}吡啶鎓 ESI-MS[M+H]+：569(计算值：569) I-22乙酸2-{4-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-2-氧代-

5-四氢-2H-吡喃-4-基-1，2-二氢嘧啶-4-基]哌嗪-1-基}吡啶鎓 ESI-MS[M+H]+：577(计算值：577) I-23乙酸2-{4-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-2-氧代-

5-丙基-1，2-二氢嘧啶-4-基]哌嗪-1-基}吡啶鎓 ESI-MS[M+H]+：535(计算值：535) I-24乙酸2-[(2-{{1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-甲基

-2-氧代-1，2-二氢嘧啶-4-基]氨基}乙基)氨基]吡啶鎓 ESI-MS[M+H]+：481(计算值：481) I-25乙酸2-[(2-{[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-2-氧代

-5-苯基-1，2-二氢嘧啶-4-基]氨基}乙基)氨基]吡啶鎓 ESI-MS[M+H]+：543(计算值：543) I-26乙酸2-[(2-{[1-(2-{[(苄氧基)羰基]氨基}-3-羧基-丙基)-2-氧

代-5-四氢-2H-吡喃-4-基-1，2-二氢嘧啶-4-基]氨基}乙基)氨基]

吡啶鎓 ESI-MS[M+H]+：551(计算值：551) I-27乙酸2-[(2-{[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-2-氧代

-5-丙基-1，2-二氢嘧啶-4-基]-氨基}乙基)氨基]吡啶鎓 ESI-MS[M+H]+：509(计算值：509) I-283-(4-[(6-{[(苄氨基)羰基]氨基}己基)氨基]-5-甲基-2-氧代嘧

啶-1(2H)-基)-N-[(苄氧基)羰基]丙氨酸 ESI-MS[M+H]+：579(计算值：579) I-29乙酸2-({[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-甲基-2-

氧代-1，2-二氢嘧啶-4-基]氨基}甲基)-5，6-二甲基-1H-苯并咪唑

-1-鎓 ESI-MS[M+H]+：519(计算值：519) I-30二乙酸2-[5-({[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-甲

基-2-氧代-1，2-二氢嘧啶-4-基]氨基}甲基)吡啶鎓-2-基]-3H-苯

并咪唑-1-鎓 ESI-MS[M+H]+：568(计算值：568) I-31三氟乙酸4-({[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-甲

基-2-氧代-1，2-二氢嘧啶-4-基]氨基}甲基)-1-吡啶-2-基哌啶鎓 ESI-MS[M+H]+：535(计算值：535) I-32乙酸[4-({[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-甲基-

2-氧代-1，2-二氢嘧啶-4-基]氨基}甲基)苯基]甲铵 ESI-MS[M+H]+：480(计算值：480) I-33(2S)-3-(4-[({1-[(苄氨基)羰基]哌啶-4-基}甲基)氨基]-5-甲基

-2-氧代嘧啶-1(2H)-基)-2-{[(苄氧基)羰基]氨基}丙酸 ESI-MS[M+H]+：577(计算值：577) I-34三氟乙酸2-[2-({[1-(2-{[(苄氧基)羰基]氨基}-3-羧基-丙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]-氨基}甲基)-1，3-噻唑-4-

基)-1H-苯并咪唑-1-鎓 ESI-MS[M+H]+：574(计算值：574) I-35三氟乙酸N-(2-{[1-(2-{[(苄氧基)羰基]氨基}-3-羧基-丙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-氨基}环己基)吡啶-2-铵 ESI-MS[M+H]+：535(计算值：535) I-36二三氟乙酸2-[({1-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基-丙

基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]-哌啶-4-基}甲基)氨]

吡啶鎓 ESI-MS[M+H]+：535(计算值：535) I-37三氟乙酸2-[2-({[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基-乙

基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}-甲基)-1，3-噻唑

-4-基]-1H-苯并咪唑-1-鎓 ESI-MS[M+H]+：560(计算值：560) I-38三氟乙酸N-(2-{[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基-乙

基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}-环己基)吡啶-2-

铵 ESI-MS[M+H]+：521(计算值：521) I-39三氟乙酸2-[5-({[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基-乙

基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}-甲基)噻吩-3-

基]-1H-苯并咪唑-1-鎓 ESI-MS[M+H]+：559(计算值：559) I-40三氟乙酸2-[({1-[1-((2S)-2-{[(苄氧基)羰基]-氨基}-2-羧基-

乙基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]哌啶-4-基}甲基)氨

基]吡啶鎓 ESI-MS[M+H]+：521(计算值：521) I-41三氟乙酸2-({2-[[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-(甲基)氨基]乙基}氨基)吡啶

鎓 ESI-MS[M+H]+：495(计算值：495) I-42三氟乙酸2-({2-[[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基](甲基)-氨基]乙基}氨

基)吡啶鎓 ESI-MS[M+H]+：481(计算值：481) I-43乙酸2-[(3-{[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}-丙酰基)氨基]-1H-咪

唑-1-鎓 ESI-MS[M+H]+：483(计算值：483) I-44乙酸2-{[3-({1-[2-羧基-1-(4-甲基苯基)乙基]-5-甲基-2-氧代-

1，2-二氢嘧啶-4-基}氨基)丙酰基]氨基}-4H-咪唑-3-鎓 ESI-MS[M+H]+：425(计算值：425) I-45乙酸2-[(3-{[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-甲基

-2-氧代-1，2-二氢嘧啶-4-基]氨基}-丙酰基)氨基]-1H-咪唑-1-

鎓 ESI-MS[M+H]+：498(计算值：498) I-46乙酸2-[(4-({[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}甲基)苄基)氨基}吡啶

鎓 ESI-MS[M+H]+：543(计算值：543) I-47(3S)-4-(4-[(4-{[(苄氨基)羰基]氨基}苄基)氨基]-5-甲基-2-氧

代嘧啶-1(2H)-基)-3-{[(苄氧基)羰基]氨基}丁酸 ESI-MS[M+H]+：599(计算值：599) I-484-(4-{[4-(1H-苯并咪唑-2-基)苄基]氨基}-5-甲基-2-氧代嘧啶-

1(2H)-基)-3-{[(苄氧基)羰基]氨基}丁酸 ESI-MS[M+H]+：567(计算值：567) I-49(2S)-3-(4-{[(2-(苄氨基)羰基]氨基}-1，3-噻唑-4基)甲基]氨

基}-5-甲基-2-氧代嘧啶-1(2H)-基)-2-{[(苄氨基)羰基]氨基}丙

酸 ESI-MS[M+H]+：592(计算值：592) I-504-(4-{[(2-{[(苄氨基)羰基]氨基}-1，3-噻唑-4-基)甲基]氨基}-

5-甲基-2-氧代嘧啶-1(2H)-基)-3-{[(苄氧基)羰基]氨基}丁酸 ESI-MS[M+H]+：606(计算值：606) I-51(2S)-3-(4-{[3-(1H-苯并咪唑-2-基)苄基]氨基}-5-甲基-2-氧代

嘧啶-1(2H)-基)-2-{[(苄氨基)羰基]氨基}丙酸 ESI-MS[M+H]+：553(计算值：553) I-52(2S)-3-(4-{[4-(1H-苯并咪唑-2-基)苄基]氨基}-5-甲基-2-氧代

嘧啶-1(2H)-基)-2-{[(苄氨基)羰基]氨基}丙酸 ESI-MS[M+H]+：553(计算值：553) I-53(2S)-3-(4-[(4-{[(苄氨基)羰基]氨基}苄基)氨基]-5-甲基-2-氧

代吡啶-1(2H)-基)-2-{[(苄氧基)羰基]氨基}丙酸 ESI-MS[M+H]+：585(计算值：585) I-54三氟乙酸2-{[4-({[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}甲基)苄基]氨基}吡啶

鎓 ESI-MS[M+H]+：557(计算值：557) I-55三氟乙酸2-{4-[({1-[2-羧基-1-(4-甲基苯基)乙基]-5-甲基-2-

氧代-1，2-二氢嘧啶-4-基}氨基)甲基]苯基}-1H-苯并咪唑-1-鎓 ESI-MS[M+H]+：494(计算值：494) I-563-(4-[(4-{[(苄氨基)羰基]氨基}苄基)氨基]-5-甲基-2-氧代嘧

啶-1(2H)-基)-3-(4-甲苯基)-丙酸 ESI-MS[M+H]+：526(计算值：526) I-573-(4-{[(2-{[(苄氨基)羰基]氨基}-1，3-噻唑-4-基)甲基]氨基}-

5-甲基-2-氧代嘧啶-1(2H)-基)-3-(4-甲苯基)丙酸 ESI-MS[M+H]+：533(计算值：533) I-58三氟乙酸2-[(3-{[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-2-氧代-5-四氢-2H-吡喃-4-基-1，2-二氢嘧啶-4-基]氨基}丙

酰基)氨基]-1H-咪唑-1-鎓 ESI-MS[M+H]+：554(计算值：554) I-59三氟乙酸2-[(3-{[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-2-氧代-5-丙基-1，2-二氢嘧啶-4-基]氨基}丙酰基)氨基]-

1H-咪唑-1-鎓 ESI-MS[M+H]+：512(计算值：512) 1-60三氟乙酸2-[(3-{[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-2-氧代-5-苯基-1，2-二氢嘧啶-4-基]氨基}丙酰基)氨基]-

1H-咪唑-1-鎓 ESI-MS[M+H]+：546(计算值：546) I-61三氟乙酸2-[(3-{[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-2-

氧代-5-四氢-2H-吡喃-4-基-1，2-二氢嘧啶-4-基]氨基}丙酰基)

氨基]-1H-咪唑-1-鎓 ESI-MS[M+H]+：568(计算值：568) I-62三氟乙酸2-[(3-{[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-2-

氧代-5-丙基-1，2-二氢嘧啶-4-基]氨基}-丙酰基)氨基]-1H-咪唑

-1-鎓 ESI-MS[M+H]+：526(计算值：526) I-63三氟乙酸2-[(3-{[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-2-

氧代-5-苯基-1，2-二氢嘧啶-4-基]氨基}-丙酰基)氨基]-1H-咪唑

-1-鎓 ESI-MS[M+H]+：560(计算值：560) I-64三氟乙酸2-[({1-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-2-氧代-5-丙基-1，2-二氢嘧啶-4-基]-哌啶-4-基}甲基)氨基]

吡啶鎓 ESI-MS[M+H]+：549(计算值：549) I-65三氟乙酸2-[({1-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-2-

氧代-5-四氢-2H-吡喃-4-基-1，2-二氢嘧啶-4-基]-哌啶-4-基}甲

基)氨基]吡啶鎓 ESI-MS[M+H]+：605(计算值：605) I-66三氟乙酸2-[({1-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-2-

氧代-5-丙基-1，2-二氢嘧啶-4-基]-哌啶-4-基}甲基)氨基]吡啶

鎓 ESI-MS[M+H]+：563(计算值：563) I-67三氟乙酸2-[({1-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-2-

氧代-5-苯基-1，2-二氢嘧啶-4-基]-哌啶-4-基}甲基)氨基]吡啶

鎓 ESI-MS[M+H]+：597(计算值：597) I-68乙酸2-{[4-({[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-

2-氧代-5-四氢-2H-吡喃-4-基-1，2-二氢嘧啶-4-基]氨基}甲基)

苄基]氨基}吡啶鎓 ESI-MS[M+H]+：613(计算值：613) I-69(2S)-3-(4-[(4-{[(苄氧基)羰基]氨基}苄基)-氨基]-2-氧代-5-

四氢-2H-吡喃-4-基嘧啶-1(2H)-基]-2-{[(苄基氧)羰基]氨基}丙

酸 ESI-MS[M+H]+：655(计算值：655) I-70乙酸2-{[4-({[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-

2-氧代-5-丙基-1，2-二氢嘧啶-4-基]氨基}甲基)苄基)氨基}吡啶

鎓 ESI-MS[M+H]+：571(计算值：571) I-713-(4-[(4-{[(苄氨基)羰基]氨基}苄基)氨基]-2-氧代-5-丙基嘧

啶-1(2H)-基)-N-[(苄氧基)羰基]丙氨酸 ESI-MS[M+H]+：613(计算值：613) I-72乙酸2-[({1-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]哌啶-4-基}甲基)氨基]-1H-

苯并咪唑-1-鎓 ESI-MS[M+H]+：560(计算值：560) I-73三氟乙酸2-[3-({[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-氨基}甲基)苯基]-1H-苯并咪

唑-1-鎓 ESI-MS[M+H]+：567(计算值：567) I-74三氟乙酸2-({[4-({[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}-甲基)噻吩-3-基]甲

基}氨基)吡啶鎓 ESI-MS[M+H]+：563(计算值：563) I-75三氟乙酸2-{4-[2-({1-[2-羧基-1-(4-甲苯基)乙基]-5-甲基-2-

氧代-1，2-二氢嘧啶-4-基}氨基)乙基]苯基}-1H-苯并咪唑-1-鎓 ESI-MS[M+H]+：508(计算值：508) I-76三氟乙酸2-[({4-[({1-[2-羧基-1-(4-甲苯基)乙基]-5-甲基-2-

氧代-1，2-二氢嘧啶-4-基}氨基)甲基]噻吩-3-基}-甲基)氨基]

吡啶鎓 ESI-MS[M+H]+：490(计算值：490) I-77三氟乙酸2-[3-({[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}-甲基)苯基]-1H-

苯并咪唑-1-鎓 ESI-MS[M+H]+：553(计算值：553) I-78三氟乙酸2-[4-(2-{[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基

乙基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}乙基)苯基]-

1H-苯并咪唑-1-鎓 ESI-MS[M+H]+：567(计算值：567) I-79三氟乙酸2-({[4-({[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基

乙基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}甲基)噻吩-3-

基]甲基}氨基)吡啶鎓 ESI-MS[M+H]+：549(计算值：549) I-80三氟乙酸2-({4-[({1-[2-羧基-1-(4-甲基苯基)乙基]-5-甲基-2-

氧代-1，2-二氢嘧啶-4-基}氨基)甲基]苄基}氨基)吡啶鎓 ESI-MS[M+H]+：484(计算值：484) I-81三氟乙酸2-[({1-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-哌啶-4-基}甲基)氨基]-1H-

苯并咪唑-1-鎓 ESI-MS[M+H]+：574(计算值：574) I-82三氟乙酸2-{[(1-{1-[2-羧基-1-(4-甲基苯基)乙基]-5-甲基-2-

氧代-1，2-二氢嘧啶-4-基}哌啶-4-基)甲基]氨基}-1H-苯并咪唑-

1-鎓 ESI-MS[M+H]+：501(计算值：501) I-83三氟乙酸2-{[4-({[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-2-氧代-5-苯基-1，2-二氢嘧啶-4-基]氨基}甲基)苄基]氨基}

吡啶鎓 ESI-MS[M+H]+：605(计算值：605) I-84(2S)-3-(4-[(4-{[(苄氨基)羰基]氨基}苄基)氨基]-2-氧代-5-苯

基嘧啶-1(2H)-基)-2-{[(苄氧基)羰基]氨基}丙酸 ESI-MS[M+H]+：647(计算值：647) I-854-(4-{[(2-{[(苄氨基)羰基]氨基}-1，3-噻唑-4-基)甲基]氨基}-

2-氧代-5-四氢-2H-吡喃-4-基-嘧啶-1(2H)-基)-3-{[(苄氧基)羰

基]氨基}丁酸 ESI-MS[M+H]+：676(计算值：676) I-864-(4-{[(2-{[(苄氨基)羰基]氨基}-1，3-噻唑-4-基)甲基]氨基}-

2-氧代-5-丙基嘧啶-1(2H)-基)-3-{[(苄氧基)羰基]氨基}丁酸 ESI-MS[M+H]+：634(计算值：634) I-874-(4-{[(2-{[(苄氨基)羰基]氨基}-1，3-噻唑-4-基)甲基]氨基}-

2-氧代-5-苯基嘧啶-1(2H)-基)-3-{[(苄氧基)羰基]氨基}丁酸 ESI-MS[M+H]+：668(计算值：668) I-88三氟乙酸2-[(3-{[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}丙基)氨基]吡啶

鎓 ESI-MS[M+H]+：481(计算值：481) I-89三氟乙酸2-[(3-{[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}丙基)氨基]吡啶鎓 ESI-MS[M+H]+：495(计算值：495) I-90三氟乙酸2-{[3-({1-[2-羧基-1-(4-甲苯基)乙基]-5-甲基-2-氧

代-1，2-二氢嘧啶-4-基}氨基)丙基]氨基}吡啶鎓 ESI-MS[M+H]+：422(计算值：422) I-91三氟乙酸2-[4-({[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}甲基)苯基]-3H-苯并咪

唑-1-鎓 ESI-MS[M+H]+：567(计算值：567) I-92乙酸2-[({1-[1-(2-羟基乙基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-

基]哌啶-4-基}甲基)氨基]吡啶鎓 ESI-MS[M+H]+：372(计算值：372) I-93乙酸2-[({1-[1-(3-羧基丙基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-

基]哌啶-4-基}甲基)氨基]吡啶鎓 ESI-MS[M+H]+：386(计算值：386) I-94乙酸2-[({1-[1-(2-羧基乙基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-

基]哌啶-4-基}甲基)氨基]-1H-苯并咪唑-1-鎓 ESI-MS[M+H]+：411(计算值：411) I-95乙酸2-[({1-[1-(3-羧基丙基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-

基]哌啶-4-基}甲基)氨基]-1H-苯并咪唑-1-鎓 ESI-MS[M+H]+：425(计算值：425) I-96乙酸2-[(3-{[1-(2-羧基乙基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-

基]氨基}丙酰基)氨基]-1H-咪唑-1-鎓 ESI-MS[M+H]+：335(计算值：335) I-97乙酸2-[(3-{[1-(3-羧基丙基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-

基]氨基}丙酰基)氨基]-1H-咪唑-1-鎓 ESI-MS[M+H]+：349(计算值：349) I-98乙酸2-[5-({[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}甲基)噻吩-2-基]-3H-

苯并咪唑-1-鎓 ESI-MS[M+H]+：559(计算值：559) I-99乙酸2-[5-({[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-甲基

-2-氧代-1，2-二氢嘧啶-4-基]-氨基}甲基)噻吩-2-基]-3H-苯并

咪唑-1-鎓 ESI-MS[M+H]+：573(计算值：573) I-100三氟乙酸2-[4-({[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}甲基)苯胺基]-

1H-苯并咪唑-1-鎓 ESI-MS[M+H]+：568(计算值：568) I-101三氟乙酸2-[4-({[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-氨基}甲基)苯胺基]-1H-苯并

咪唑-1-鎓 ESI-MS[M+H]+：582(计算值：582) I-102三氟乙酸2-[({1-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-哌啶-4-基}甲基)氨基]-

1，4，5，6-四氢-嘧啶-1-鎓 ESI-MS[M+H]+：540(计算值：540) I-103三氟乙酸N-{1-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]-哌啶-4-基}吡啶-2-铵 ESI-MS[M+H]+：507(计算值：507) I-104乙酸2-[(3-{[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}丙酰基)氨基]-1H-苯

并咪唑-1-鎓 ESI-MS[M+H]+：534(计算值：534) I-105乙酸2-[(3-{[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}丙酰基)氨基]-5，6-二

甲基-1H-苯并咪唑-1-鎓 ESI-MS[M+H]+：562(计算值：562) I-106三氟乙酸2-[(3-{[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}丙酰基)氨基]-1H-苯并

咪唑-1-鎓 ESI-MS[M+H]+：548(计算值：548) I-107三氟乙酸2-[(3-{[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}丙酰基)氨基]-5，6-二甲

基-1H-苯并咪唑-1-鎓 ESI-MS[M+H]+：576(计算值：576) I-108三氟乙酸2-[(3-{[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}丙基)氨基]吡啶

鎓 ESI-MS[M+H]+：481(计算值：481) I-109乙酸2-[4-(2-{[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙

基)-5-甲基-2-氧代-1，2-二氢嘧啶-4-基]氨基}乙基)苯基]-1H-

苯并咪唑-1-鎓 ESI-MS[M+H]+：567(计算值：567) I-110乙酸2-[({1-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]哌啶-4-基}羰基)氨基]吡啶

鎓 ESI-MS[M+H]+：535(计算值：535) I-111乙酸2-[({1-[1-((2S)-2-{[(苄氧基)羰基]氨基}-2-羧基乙基)-

5-甲基-2-氧代-1，2-二氢嘧啶-4-基]哌啶-4-基}羰基)氨基]-3H-

苯并咪唑-1-鎓 ESI-MS[M+H]+：574(计算值：574) I-112三氟乙酸2-[({1-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)-5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-哌啶-4-基}羰基)氨基]吡啶

鎓 ESI-MS[M+H]+：549(计算值：549) I-113三氟乙酸2-[({1-[1-(2-{[(苄氧基)羰基]氨基}-3-羧基丙基)5-

甲基-2-氧代-1，2-二氢嘧啶-4-基]-哌啶-4-基}羰基)氨基]吡啶

鎓 ESI-MS[M+H]+：588(计算值：588) II生物学实施例 实施例1 整合素αvβ3测定

用一种实验系统，进行整合素αvβ3配体的鉴定和评价。此系统基于 天然整合素αvβ3配体玻连蛋白和实验物质对固相结合的整合素αvβ3 的结合之间的竞争。 步骤： -用pH为9.2的含有250ng/ml整合素αvβ3的0.05MNaHCO3涂覆微量滴 定板；0.1ml/孔； -用1％奶粉/测定缓冲液饱和；0.3ml/孔；0.5h/室温 -用0.05％吐温20/测定缓冲液洗涤三次 -含有实验物质的0.1％奶粉/测定缓冲液，50μl/孔+含有0μg/ml或2 μg/ml人玻连蛋白(BoehringerIngelheimT007)的0.1％奶粉/测定 缓冲液，50μl/孔；1h/室温 -用0.05％吐温20/测定缓冲液洗涤三次 -含有与过氧化物酶偶合的1μg/ml人玻连蛋白抗体(KordiaSAVN- APHRP)的0.1％奶粉/测定缓冲液，0.1ml/孔；1h/室温 -用0.05％吐温20/测定缓冲液洗涤三次 -0.1ml/孔过氧化物酶底物 -用0.1ml/孔2MH2SO4终止反应 -测定在450nm的吸收 整合素αvβ3：用Nonidet增溶人胎盘，并对整合素αvβ3在GRGDSPK基 质上进行亲和纯化(用EDTA洗脱)。用阴离子交换层析去除由整合素αIIbβ3 和人血清白蛋白、以及洗涤剂和EDTA所致的污染。

测定缓冲液：50mMTrispH7.5；100mMNaCl；1mMCaCl2；1mMMgCl2； 10μMMnCl2。

过氧化物酶底物：将0.1ml的TMB溶液(42mMTMB在DMSO中)与10ml 底物缓冲液(0.1M乙酸钠pH4.9)混合，并然后加入14.7μl的3％H2O2。

在测定中使用各种稀释的实验物质，确定IC50值(50％配体被置换时 的配体的浓度)。在此方法中，来自于实施例I-40、I-45、I-54、I-61、 I-63、I-64、I-72和I-49的化合物显示了最好的结果。 实施例2 整合素αIIbβ3测定

测定基于天然整合素αIIbβ3配体血纤蛋白原和实验物质对整合素 αIIbβ3的结合之间的竞争。

步骤： -用pH为9.2的含有10μg/ml血纤蛋白原(Calbiochem341578)的0.05M NaHCO3涂覆微量滴定板；0.1ml/孔； -用1％BSA/PBS饱和；0.3ml/孔；30分钟/室温 -用0.05％吐温20/PBS洗涤三次 -含有实验物质的0.1％BSA/PBS；50μl/孔+含有200μg/ml整合素αIIbβ3 (Kordia)的0.1％BSA/PBS；50μl/孔；2至4h/室温 -如上所述洗涤三次 -生物素化的抗整合素αIIbβ3抗体(DianovaCBL130B)；1∶1000含于 0.1％BSA/PBS中；0.1ml/孔；2至4h/室温 -如上所述洗涤三次 -链霉抗生物素蛋白-过氧化物酶复合物(B.M.1089153)，1∶10,000 含于0.1％BSA/PBS中；0.1ml/孔；30分钟/室温 -如上所述洗涤三次 -0.1ml/孔过氧化物酶底物 -用0.1ml/孔2MH2SO4终止反应 -测定在450nm的吸收

过氧化物酶底物：将0.1ml的TMB溶液(42mMTMB在DMSO中)与10ml 底物缓冲液(0.1M乙酸钠pH4.9)混合，然后加入14.7μl的3％H2O2。

在测定中使用各种稀释的实验物质，确定IC50值(50％配体被置换时 的拮抗剂的浓度)。通过比较在整合素αvβ3和整合素αIIbβ3测定中的 IC50值，确定物质的选择性。 实施例3 CAM测定

为了测定整合素αvβ3拮抗剂的体内活性，通常采用CAM(绒膜尿囊 膜)测定。它基于肿瘤组织的血管生成和新血管生成的抑制作用(Am.J. Pathol.1975，79，597-618；CancerRes.1980，40，2300-2309；Nature 1987，329，630)。操作与现有技术相似。鸡胚胎血管和移植的肿瘤组织 的生长可很容易被跟踪和评价。 实施例4 兔眼测定

与实施例3相似，在该体内模型中，跟踪和评价在整合素αvβ3拮抗 剂存在下，血管生成和新血管生成的抑制。此模型是被普遍承认的，它 是基于从边缘开始进入兔眼角膜的血管的生长(Proc.Natl.Acad. Sci.USA.1994，91，4082-4085；Science1976，193，70-72)。操作与现 有技术相似。