Discovery of N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea as a potent TRPV1 antagonistic template

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• 作者：Jihyae Ann^a ; ^&dagger ; ; Wei Sun^b ; ^&dagger ; ; Xing Zhou^c ; Aeran Jung^a ; Jisoo Baek^a ; Sunho Lee^a ; Changhoon Kim^a ; Suyoung Yoon^a ; Sunhye Hong^d ; Sun Choi^d ; Noe A. Turcios^e ; Brienna K.A. Herold^e ; Timothy E. Esch^e ; Nancy E. Lewin^e ; Adelle Abramovitz^e ; Larry V. Pearce^e ; Peter M. Blumberg^e ; 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 Letters
• 出版年：2016
• 出版时间：1 August 2016
• 年：2016
• 卷：26
• 期：15
• 页码：3603-3607
• 全文大小：1326 K

文摘

A series of homologous analogues of prototype antagonist 1 and its urea surrogate were investigated as hTRPV1 ligands. Through one-carbon elongation in the respective pharmacophoric regions, N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea was identified as a novel and potent TRPV1 antagonistic template. Its representative compound 27 showed a potency comparable to that of lead compound 1. Docking analysis of compound 27 in our hTRPV1 homology model indicated that its binding mode was similar with that of 1S.