Basic Information
ID: ALA4808213
Journal: Bioorg Med Chem Lett
Title: 2-(Halogenated Phenyl) acetamides and propanamides as potent TRPV1 antagonists.
Authors: Kang JM, Kwon SO, Ann J, Lee S, Kim C, Do N, Jeong JJ, Blumberg PM, Ha H, Vu TNL, Yoon S, Choi S, Frank-Foltyn R, Lesch B, Bahrenberg G, Stockhausen H, Christoph T, Lee J.
Abstract: A series consisting of 117 2-(halogenated phenyl) acetamide and propanamide analogs were investigated as TRPV1 antagonists. The structure-activity analysis targeting their three pharmacophoric regions indicated that halogenated phenyl A-region analogs exhibited a broad functional profile ranging from agonism to antagonism. Among the compounds, antagonists 28 and 92 exhibited potent antagonism toward capsaicin for hTRPV1 with Ki[CAP] = 2.6 and 6.9 nM, respectively. Further, antagonist 92 displayed promising analgesic activity in vivo in both phases of the formalin mouse pain model. A molecular modeling study of 92 indicated that the two fluoro groups in the A-region made hydrophobic interactions with the receptor.
CiteXplore: 34273488
DOI: 10.1016/j.bmcl.2021.128266
Patent ID: ┄
Associated Items: Associated Bioactivities Associated Assays Associated Compounds Associated Targets