2-(Halogenated Phenyl) acetamides and propanamides as potent TRPV1 antagonists
- 주제(키워드) Analgesic , TRPV1 Antagonist , Vanilloid Receptor 1
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier Ltd
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000182154
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bmcl.2021.128266
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
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. © 2021 Elsevier Ltd
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