Isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives as potent alpha(4)beta(1) integrin antagonists

Authors
Duplantier, AJ Beckius, GE Chambers, RJ Chupak, LS Jenkinson, TH Klein, AS Kraus, KG Kudlacz, EM McKechney, MW Pettersson, M Whitney, CA Milici, AJ
Citation
Aj. Duplantier et al., Isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives as potent alpha(4)beta(1) integrin antagonists, BIOORG MED, 11(19), 2001, pp. 2593-2596
Citations number
21
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
19
Year of publication
2001
Pages
2593 - 2596
Database
ISI
SICI code
0960-894X(20011008)11:19<2593:IOATAD>2.0.ZU;2-K
Abstract
A series of isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives d erived from LDV was found to be a potent antagonist of the alpha (4)beta (1 ) integrin. The synthesis and SAR leading up to 3-[3-(1-{2-[3-methoxy-4-(3- o-tolyl-ureido)-phenyl]-acetylamino}-3-methyl-butyl)-isoxazol-5-yl]-propion ic acid (22) are reported, In an allergic mouse model, compound 22 was effi cacious delivered systemically (58% inhib ((a) over bar; 10 mg/kg, sc) as w ell as by intra-tracheal instillation (ED50 = 2 mug/kg). (C) 2001 Elsevier Science Ltd. All rights reserved.