2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists

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• 作者：Jihyae Ann^a ; Yooran Ki^a ; Suyoung Yoon^a ; Myeong Seop Kim^a ; Jung-Un Lee^a ; Changhoon Kim^a ; Sunho Lee^a ; Aeran Jung^a ; Jisoo Baek^a ; Sunhye Hong^b ; Sun Choi^b ; Larry V. Pearce^c ; Timothy E. Esch^c ; Noe A. Turcios^c ; Nancy E. Lewin^c ; Adebowale E. Ogunjirin^c ; Brienna K.A. Herold^c ; Anna K. McCall^c ; Peter M. Blumberg^c ; Jeewoo Lee^a ; ^{jeewoo@snu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Vanilloid receptor 1 ; TRPV1 antagonists ; Analgesic
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 March 2016
• 年：2016
• 卷：24
• 期：6
• 页码：1231-1240
• 全文大小：2805 K

文摘

A series of 2-sulfonamidopyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide were investigated as hTRPV1 ligands. Systematic modification on the 2-sulfonamido group provided highly potent TRPV1 antagonists. The N-benzyl phenylsulfonamide derivatives 12 and 23 in particular showed higher affinities than that of lead compound 1. Compound 12 exhibited strong analgesic activity in the formalin pain model. Docking analysis of its chiral S-form 12S in our hTRPV1 homology model indicated that its high affinity might arise from additional hydrophobic interactions not present in lead compound 1S.