Discovery of potent and selective β-homophenylalanine based dipeptidyl peptidase IV inhibitors

被引：50

作者：

Xu, JY

Ok, HO

Gonzalez, EJ

Colwell, LF

Habulihaz, B

He, HB

Leiting, B

Lyons, KA

Marsilio, F

Patel, RA

Wu, JK

Thornberry, NA

Weber, AE

Parmee, ER

机构：

[1] Merck & Co Inc, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Dept Metab Dis, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 18期

关键词：

DP-IV;

D O I：

10.1016/j.bmcl.2004.06.099

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Modification of in-house screening lead beta-aminoacyl proline 8 gave an equipotent thiazolidide 9. Extensive SAR studies on the phenyl ring of 9 led to the discovery of a novel series of potent and selective DP-IV inhibitors. Introduction of a fluorine at the 2-position proved to be crucial for the potency of this series. The 2,5-difluoro (22q) and 2,4,5-trifluoro (22t) analogues were potent inhibitors of DP-IV (IC50=270, 119nM, respectively). (C) 2004 Elsevier Ltd. All rights reserved.

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收藏

页码：4759 / 4762

页数：4

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