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Pyridine C-region analogs of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.

Authors :
Ryu H
Seo S
Lee JY
Ha TH
Lee S
Jung A
Ann J
Kim SE
Yoon S
Hong M
Blumberg PM
Frank-Foltyn R
Bahrenberg G
Schiene K
Stockhausen H
Christoph T
Frormann S
Lee J
Source :
European journal of medicinal chemistry [Eur J Med Chem] 2015 Mar 26; Vol. 93, pp. 101-8. Date of Electronic Publication: 2015 Feb 02.
Publication Year :
2015

Abstract

A series of pyridine derivatives in the C-region of N-((6-trifluoromethyl-pyridin-3-yl)methyl) 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. The SAR analysis indicated that 6-difluorochloromethyl pyridine derivatives were the best surrogates of the C-region for previous leads. Among them, compound 31 showed excellent antagonism to capsaicin as well as to multiple hTRPV1 activators. It demonstrated strong analgesic activity in the formalin test in mice with full efficacy and it blocked capsaicin-induced hypothermia in vivo.<br /> (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Details

Language :
English
ISSN :
1768-3254
Volume :
93
Database :
MEDLINE
Journal :
European journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
25659771
Full Text :
https://doi.org/10.1016/j.ejmech.2015.02.001