α-Methylated simplified resiniferatoxin (sRTX) thiourea analogues as potent and stereospecific TRPV1 antagonists

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:24

Article

Kim, Ho Shin¹  Jin, Mi-Kyoung¹  Kang, Sang-Uk¹  Lim, Ju-Ok¹  Phuong-Thao Tran¹  Van-Hai Hoang¹  Ann, Jihyae¹  Ha, Tae-Hwan¹  Pearce, Larry V.²  Pavlyukovets, Vladimir A.²  Blumberg, Peter M.²  Lee, Jeewoo¹ 

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

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

关键词: Vanilloid receptor 1;    TRPV1 antagonist;    Capsaicin;    Resiniferatoxin;   

DOI  :  10.1016/j.bmcl.2014.04.054

来源: Elsevier

【 摘 要 】

A series of alpha-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of alpha-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high binding affinity and potent antagonism while the configuration of the C-region was not significant. (C) 2014 Elsevier Ltd. All rights reserved.

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