Synthesis and structure-activity relationships of potent and orally activesulfonamide ETB selective antagonists

Citation
Y. Kanda et al., Synthesis and structure-activity relationships of potent and orally activesulfonamide ETB selective antagonists, BIO MED CH, 9(4), 2001, pp. 897-907
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY
ISSN journal
0968-0896 → ACNP
Volume
9
Issue
4
Year of publication
2001
Pages
897 - 907
Database
ISI
SICI code
0968-0896(200104)9:4<897:SASROP>2.0.ZU;2-J
Abstract
The synthesis and structure-activity relationships of a series of N-pyrimid inyl benzenesulfonamides as ETB selective antagonists are described. N-Isox azolyl benzenesulfonamide 1a. previously reported,(1) was selected as a lea d compound, and isosteric replacement of the isoxazole ring of la with a py rimidine ring led to the discovery of the highly potent ETB selective antag onist 6e with oral bioavailability. Modification of the terminal aldehyde g roup at the 6-position of the pyrimidine ring was investigated, and malonat e 15b and acylhydrazone 16f were found to be equipotent to aldehyde 6e. Com pound 6e showed ETB antagonistic activity on in vivo evaluation. (C) 2001 E lsevier Science Ltd. All rights reserved.