Studies on analgesic oligopeptides. II. Structure-activity relationship among thirty analogs of a cyclic dipeptide, cyclo(-Tyr-Arg-)

Publisher Website
Google Scholar
Abstract
Thirty diketopiperazines were synthesized as analogs of cyclo(-Tyr-Arg-). The analgesic activities of these analogs were evaluated after intracerebral administration in mice. In the cyclo(-X-Arg-) series of analogs, cyclo[-Tyr(Et)-Arg-] showed the most potent activity. In the cyclo(-Tyr-Y-) series of analogs, the activity decreased in the order Y = homoarginine, p-guanidinophenylalanine, 2-amino-4-guanidinobutyric acid, Lys, Orn, His, .alpha.,.gamma.-diaminobutyric acid and Pro. Among the analogs synthesized, cyclo[-Tyr(Et)-Har-], which was designed on the basis of the above results, exhibited remarkably potent analgesic activity, being 17 times more potent than cyclo(-Tyr-Arg-) and nearly as potent as morphine on a mol basis. The structure-activity relation of cyclo(-Tyr-Arg-) is discussed in the light of these results.

This publication has 0 references indexed in Scilit: