α-甲基化简化树脂毒素（sRTX）硫脲类似物作为有效的立体特异性瞬时受体电位香草酸亚型1（TRPV1）拮抗剂。
α-Methylated simplified resiniferatoxin (sRTX) thiourea analogues as potent and stereospecific TRPV1 antagonists.
作者信息
Kim Ho Shin, Jin Mi-Kyoung, Kang Sang-Uk, Lim Ju-Ok, Tran Phuong-Thao, Hoang Van-Hai, Ann Jihyae, Ha Tae-Hwan, Pearce Larry V, Pavlyukovets Vladimir A, Blumberg Peter M, Lee Jeewoo
机构信息
Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
出版信息
Bioorg Med Chem Lett. 2014 Jun 15;24(12):2685-8. doi: 10.1016/j.bmcl.2014.04.054. Epub 2014 Apr 23.
Abstract
A series of α-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of α-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.
摘要
为了研究α-甲基化对受体活性的影响，对一系列强效sRTX硫脲拮抗剂的α-甲基化类似物作为rTRPV1配体进行了研究。构效关系分析表明，活性具有立体特异性，新形成的手性中心的(R)-构型具有高结合亲和力和强效拮抗作用，而C区域的构型并不重要。
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