title: A novel class of enkephalinase inhibitors containing a C-terminal sulfo group.
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.
authors.affiliation: Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mimura
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: J
authors.initials: J
authors.lastname: Nishino
authors.forename: T
authors.initials: T
authors.lastname: Sawayama
authors.forename: T
authors.initials: T
authors.lastname: Komiya
authors.forename: T
authors.initials: T
authors.lastname: Deguchi
authors.forename: A
authors.initials: A
authors.lastname: Kita
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: J
authors.initials: J
authors.lastname: Matsumoto
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D051379:Mice; D008968:Molecular Conformation; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011817:Rabbits; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000700:Analgesics; D004791:Enzyme Inhibitors; D013451:Sulfonic Acids; D015260:Neprilysin