Enkephalinase inhibitors. 1. 2,4-Dibenzylglutaric acid derivatives.
The synthesis of two new series of dicarboxylic acid dipeptides and two sulfhydryl-containing inhibitors are described. The in vitro enkephalinase inhibition data and some in vivo analgesic data are presented for these compounds. For the dibenzylglutaric acid series structure-activity relationships and in vivo analgesic activity are discussed. The reverse amides, i.e., 4-amino-2,4-dibenzylbutyric acid derivatives, are also discussed. Two sulfhydryl-containing inhibitors showed good in vivo potency in the mouse jump-latency hot-plate test after peripheral administration at moderate low doses.
Ksander
G M
GM
Research Department, CIBA-GEIGY Corporation, Summit, New Jersey 07901.
Diefenbacher
C G
CG
Yuan
A M
AM
Clark
F
F
Sakane
Y
Y
Ghai
R D
RD
D000700:Analgesics / Q000138:chemical synthesis; D000818:Animals; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D001812:Blood-Brain Barrier; D055598:Chemical Phenomena; D002621:Chemistry; D003461:Crystallography; D005977:Glutarates / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000700:Analgesics; D001593:Benzyl Compounds; D005977:Glutarates; D015260:Neprilysin