Boro-norleucine as a P1 residue for the design of selective and potent DPP7 inhibitors

被引：14

作者：

Shreder, KR ^{[1
]}

Wong, MS ^{[1
]}

Corral, S ^{[1
]}

Yu, ZZ ^{[1
]}

Winn, DT ^{[1
]}

Wu, M ^{[1
]}

Hu, Y ^{[1
]}

Nomanbhoy, T ^{[1
]}

Alemayehu, S ^{[1
]}

Fuller, SR ^{[1
]}

Rosenblum, JS ^{[1
]}

Kozarich, JW ^{[1
]}

机构：

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

来源：

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

关键词：

dipeptidyl peptidase; boro-norleucine; DPP4; FAP; DPP7; DPP8; DPP9;

D O I：

10.1016/j.bmcl.2005.06.076

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Dipeptide-based inhibitors with C-substituted (alkyl or aminoalkyl) alpha-amino acids in the P2 position and born-norleucine (boro-Nle) in the P1 position were synthesized. Relative to born-proline, boro-Nle as a P1 residue was shown able to significantly dial out DPP4, FAP, DPP8, and DPP9 activity. Dab-boro-Nle (4g) proved to be the most selective and potent DPP7 inhibitor with a DPP7 IC50 value of 480 pM. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：4256 / 4260

页数：5

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