The SAR analysis of TRPV1 agonists with the α-methylated B-region

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Cho, Yongsung¹  Kim, Myeong Seop¹  Kim, Ho Shin¹  Ann, Jihyae¹  Lee, Jiyoun²  Pearce, Larry V.³  Pavlyukovets, Vladimir A.³  Morgan, Matthew A.³  Blumberg, Peter M.³  Lee, Jeewoo¹ 

[1] Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea

[2] Sungshin Womens Univ, Dept Global Med Sci, Seoul 142732, South Korea

[3] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

关键词: Vanilloid receptor 1;    TRPV1 agonist;    Capsaicin;   

DOI  :  10.1016/j.bmcl.2012.06.059

来源: Elsevier

【 摘 要 】

A series of TRPV1 agonists with amide, reverse amide, and thiourea groups in the B-region and their corresponding alpha-methylated analogues were investigated. Whereas the alpha-methylation of the amide B-region enhanced the binding affinities and potencies as agonists, that of the reverse amide and thiourea led to a reduction in receptor affinity. The analysis indicated that proper hydrogen bonding as well as steric effects in the B-region are critical for receptor binding. (c) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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