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Discovery of indane propanamides as potent and selective TRPV1 antagonists.

Authors :
Ahn S
Kim YS
Kim MS
Ann J
Ha H
Yoo YD
Kim YH
Blumberg PM
Frank-Foltyn R
Bahrenberg G
Stockhausen H
Christoph T
Lee J
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Feb 01; Vol. 30 (3), pp. 126838. Date of Electronic Publication: 2019 Dec 03.
Publication Year :
2020

Abstract

A series of indane-type acetamide and propanamide analogues were investigated as TRPV1 antagonists. The analysis of structure-activity relationship indicated that indane A-region analogues exhibited better antagonism than did the corresponding 2,3-dihydrobenzofuran and 1,3-benzodioxole surrogates. Among them, antagonist 36 exhibited potent and selective antagonism toward capsaicin for hTRPV1 and mTRPV1. Further, in vivo studies indicated that antagonist 36 showed excellent analgesic activity in both phases of the formalin mouse pain model and inhibited the pain behavior completely at a dose of 1 mg/kg in the 2nd phase.<br /> (Copyright © 2019. Published by Elsevier Ltd.)

Details

Language :
English
ISSN :
1464-3405
Volume :
30
Issue :
3
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
31864799
Full Text :
https://doi.org/10.1016/j.bmcl.2019.126838