Kang Dong Wook, Ryu Hyungchul, Lee Jeewoo, Lang Krystle A, Pavlyukovets Vladimir A, Pearce Larry V, Ikeda Tetsurou, Lazar Jozsef, Blumberg Peter M
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Bioorg Med Chem Lett. 2007 Jan 1;17(1):214-9. doi: 10.1016/j.bmcl.2006.09.059. Epub 2006 Oct 10.
Selected potent TRPV1 agonists (1-6) have been modified by 5- or 6-halogenation on the aromatic A-region to analyze their effects on potency and efficacy (agonism versus antagonism). The halogenation caused enhanced functional antagonism at TRPV1 compared to the corresponding prototype agonists. The analysis of SAR indicated that the antagonism was enhanced as the size of the halogen increased (I>Br>Cl) and when the 6-position was halogenated. Compounds 23c and 31b were found to be potent full antagonists with K(i) (as functional antagonist)=23.1 and 30.3 nM in rTRPV1/CHO system, respectively.
已通过对芳香A区域进行5-或6-卤代修饰选定的强效TRPV1激动剂（1-6），以分析其对效力和功效（激动与拮抗）的影响。与相应的原型激动剂相比，卤代导致TRPV1的功能性拮抗作用增强。构效关系分析表明，随着卤素尺寸的增加（I>Br>Cl）以及当6-位被卤代时，拮抗作用增强。在rTRPV1/CHO系统中，发现化合物23c和31b分别是强效的完全拮抗剂，其K(i)（作为功能性拮抗剂）=23.1和30.3 nM。
