Dibasic inhibitors of human mast cell tryptase. Part 2: Structure-activity relationships and requirements for potent activity

被引：35

作者：

Rice, KD

Wang, VR

Gangloff, AR

Kuo, EYL

Dener, JM

Newcomb, WS

Young, WB

Putnam, D

Cregar, L

Wong, M

Simpson, PJ

机构：

[1] Axys Pharmaceut Inc, Dept Med Chem, S San Francisco, CA 94080 USA

[2] Axys Pharmaceut Inc, Dept Enzymol, S San Francisco, CA 94080 USA

[3] Exelixis Pharmaceut Inc, S San Francisco, CA 94080 USA

[4] ChemRx Adv Technol, S San Francisco, CA 94080 USA

[5] Argonaut Technol Inc, San Carlos, CA 94070 USA

[6] Genesoft Inc, S San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(00)00485-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Detailed structure-activity relationships (SARs) for a series of dibasic human tryptase inhibitors are presented. The structural requirements for potent inhibitory activity are remarkably broad with a range of core template modifications being well tolerated. Optimized inhibitors demonstrate potent anti-asthmatic activity in a sheep model of allergic asthma. APC-2059, a dibasic tryptase inhibitor with subnanomolar activity, has been advanced to phase II clinical trials for the treatment of both psoriasis and ulcerative colitis. (C) 2000 Published by Elsevier Science Ltd.

引用

页码：2361 / 2366

页数：6

共 10 条

[1] TRYPTASE INHIBITORS BLOCK ALLERGEN-INDUCED AIRWAY AND INFLAMMATORY RESPONSES IN ALLERGIC SHEEP [J].