Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Bioorg Med Chem. 2012 Jan 1;20(1):215-24. doi: 10.1016/j.bmc.2011.11.008. Epub 2011 Nov 22.
Structure-activity relationships for the A-region in a series of N-4-t-butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamides as TRPV1 antagonists have been investigated. Among them, the 3-fluoro analogue 54 showed high binding affinity and potent antagonism for both rTRPV1 and hTRPV1 in CHO cells. Its stereospecific activity was demonstrated with marked selectivity for the (S)-configuration (54S versus 54R). A docking study of 54S with our hTRPV1 homology model highlighted crucial hydrogen bonds between the ligand and the receptor contributing to its potency.
我们研究了一系列 N-4-叔丁基苄基 2-(4-甲磺酰氨基苯基)丙酰胺中 A 区域的构效关系，作为 TRPV1 拮抗剂。其中，3-氟类似物 54 对 rTRPV1 和 hTRPV1 在 CHO 细胞中的结合亲和力和拮抗作用都很强。其立体特异性活性表现为对（S）构型（54S 对 54R）具有显著的选择性。54S 与我们的 hTRPV1 同源模型的对接研究强调了配体与受体之间的氢键对其活性的重要性。
