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

Article abstract of 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.