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The SAR analysis of TRPV1 agonists with the α-methylated B-region.

Authors :
Cho Y
Kim MS
Kim HS
Ann J
Lee J
Pearce LV
Pavlyukovets VA
Morgan MA
Blumberg PM
Lee J
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2012 Aug 15; Vol. 22 (16), pp. 5227-31. Date of Electronic Publication: 2012 Jun 23.
Publication Year :
2012

Abstract

A series of TRPV1 agonists with amide, reverse amide, and thiourea groups in the B-region and their corresponding α-methylated analogues were investigated. Whereas the α-methylation of the amide B-region enhanced the binding affinities and potencies as agonists, that of the reverse amide and thiourea led to a reduction in receptor affinity. The analysis indicated that proper hydrogen bonding as well as steric effects in the B-region are critical for receptor binding.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
22
Issue :
16
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
22796184
Full Text :
https://doi.org/10.1016/j.bmcl.2012.06.059