Document Report Card

ID: ALA1126159

Journal: J Med Chem

Title: A novel class of enkephalinase inhibitors containing a C-terminal sulfo group.

Authors: Mimura T, Nakamura Y, Nishino J, Sawayama T, Komiya T, Deguchi T, Kita A, Nakamura H, Matsumoto J.

Abstract: 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.

CiteXplore: 1738153

DOI: 10.1021/jm00081a024