Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 25, Issue 11, Pages 2326-2330Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2015.04.024
Keywords
TRPV1 antagonist; Analgesic; Capsaicin; Molecular modeling
Categories
Funding
- Grunenthal in Germany
- Korea Science and Engineering Foundation (KOSEF) [NRF-2014M3A9B5073755]
- National Leading Research Lab (NLRL) program in South Korea [2011-0028885]
- Intramural Research Program of NIH, Center for Cancer Research, NCI in USA [Z1A BC 005270]
- National Research Foundation of Korea [2011-0028885] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
A series of alpha-substituted acetamide derivatives of previously reported 2-(3-fluoro-4-methylsulfonamidophenyl) propanamide leads (1, 2) were investigated for antagonism of hTRPV1 activation by capsaicin. Compound 34, which possesses an alpha-m-tolyl substituent, showed highly potent and selective antagonism of capsaicin with K-i(CAP) = 0.1 nM. It thus reflected a 3-fold improvement in potency over parent 1. Docking analysis using our homology model indicated that the high potency of 34 might be attributed to a specific hydrophobic interaction of the m-tolyl group with the receptor. (C) 2015 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available
Share Paper
