Mimura T, Nakamura Y, Nishino J, Sawayama T, Komiya T, Deguchi T, Kita A, Nakamura H, Matsumoto J
Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
J Med Chem. 1992 Feb 7;35(3):602-8. doi: 10.1021/jm00081a024.
A new series of sulfonic acids were synthesized and tested for their enkephalinase inhibitory activity. Among them, the most potent was N-(2-benzyl-3-mercaptopropionyl)metanilic acid 10i with an IC50 value of 0.27 nM. Several other analogues (10a,b,j,n,o,gg,hh) showed the inhibitory activity comparable to or greater than thiorphan (IC50 = 2.6 nM), a C-terminal carboxyl-containing inhibitor of enkephalinase. Thus compounds containing a C-terminal sulfo group, instead of the C-terminal carboxyl group, were found to show a remarkably high level of inhibition of enkephalinase. The analgesic activity of 10b, (S)-10b, and (R)-10b was also evaluated by the phenylbenzoquinone writhing test.
合成了一系列新的磺酸，并对其脑啡肽酶抑制活性进行了测试。其中，活性最强的是N-(2-苄基-3-巯基丙酰)间氨基苯磺酸10i，其IC50值为0.27 nM。其他几种类似物(10a、b、j、n、o、gg、hh)的抑制活性与脑啡肽酶的C末端含羧基抑制剂硫磷酰胺(IC50 = 2.6 nM)相当或更高。因此，发现含有C末端磺酸基而非C末端羧基的化合物对脑啡肽酶具有显著的高抑制水平。还通过苯醌扭体试验评估了10b、(S)-10b和(R)-10b的镇痛活性。
