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

Authors
Rice, KD Wang, VR Gangloff, AR Kuo, EYL Dener, JM Newcomb, WS Young, WB Putnam, D Cregar, L Wong, M Simpson, PJ
Citation
Kd. Rice et al., Dibasic inhibitors of human mast cell tryptase. Part 2: Structure-activityrelationships and requirements for potent activity, BIOORG MED, 10(20), 2000, pp. 2361-2366
Citations number
10
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
10
Issue
20
Year of publication
2000
Pages
2361 - 2366
Database
ISI
SICI code
0960-894X(20001016)10:20<2361:DIOHMC>2.0.ZU;2-U
Abstract
Detailed structure-activity relationships (SARs) for a series of dibasic hu man tryptase inhibitors are presented. The structural requirements for pote nt inhibitory activity are remarkably broad with a range of core template m odifications being well tolerated. Optimized inhibitors demonstrate potent anti-asthmatic activity in a sheep model of allergic asthma. APC-2059, a di basic tryptase inhibitor with subnanomolar activity, has been advanced to p hase II clinical trials for the treatment of both psoriasis and ulcerative colitis. (C) 2000 Published by Elsevier Science Ltd.