Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7

被引：32

作者：

Hu, Y ^{[1
]}

Ma, LF ^{[1
]}

Wu, M ^{[1
]}

Wong, MS ^{[1
]}

Li, B ^{[1
]}

Corral, S ^{[1
]}

Yu, ZZ ^{[1
]}

Nomanbhoy, T ^{[1
]}

Alemayehu, S ^{[1
]}

Fuller, SR ^{[1
]}

Rosenblum, JS ^{[1
]}

Rozenkrants, N ^{[1
]}

Minimo, LC ^{[1
]}

Ripka, WC ^{[1
]}

Szardenings, AK ^{[1
]}

Kozarich, JW ^{[1
]}

Shreder, KR ^{[1
]}

机构：

[1] ActivX Biosci Inc, La Jolla, CA 92037 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 19期

关键词：

dipeptidyl peptidase; boro-Pro; DPP4; FAP; DPP7;

D O I：

10.1016/j.bmcl.2005.06.075

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPPs) was studied. In a series of N'-cycloalkyl analogs, DPP4 and fibroblast activation protein-alpha (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs. (c) 2005 Elsevier Ltd. All rights reserved.

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收藏

页码：4239 / 4242

页数：4

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