Design, syntheses, and structure-activity relationships of indan derivatives as endothelin antagonists; New lead generation of non-peptidic antagonist from peptidic leads

Citation
H. Morimoto et al., Design, syntheses, and structure-activity relationships of indan derivatives as endothelin antagonists; New lead generation of non-peptidic antagonist from peptidic leads, BIO MED CH, 9(2), 2001, pp. 255-268
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY
ISSN journal
0968-0896 → ACNP
Volume
9
Issue
2
Year of publication
2001
Pages
255 - 268
Database
ISI
SICI code
0968-0896(200102)9:2<255:DSASRO>2.0.ZU;2-J
Abstract
A new lead generation of non-peptidic ETA antagonists from two peptidic ETA -selective ones. BQ-123 and FR139317, was performed. Using computer assiste d molecular modeling, a putative pharmacophore was constructed from the sup erposition of the reported three-dimensional structure of the cyclic peptid e BQ-123 and a presumable beta -turn active conformation of the linear pept ide FR139317 formed by an intramolecular hydrogen bond. According to this m odel, a new series of indan derivatives were designed and synthesized. Amon g these, 5-isobutyrylamino-6-(1-naphthylmethyloxy)-3-(2-thienyl)-3-indancar boxylic acid (1b) showed a moderate ETA antagonistic activity (IC50=28 muM) . (C) 2001 Elsevier Science Ltd. All rights reserved.