Structure-activity relationships of dermorphin analogues containing chiral piperazin-2-one and piperazine derivatives.
The amide and ester carbonyl groups of four piperazin-2-one derivatives (N,N'-ethylene-bridged dipeptide ethyl esters) constructed from (R)- or (S)-phenylalanine and glycine were reduced with borane-tetrahydrofuran complex to produce the corresponding piperazine derivatives in 70-80% yields. These piperazin-2-one or piperazine derivatives were used as the carboxyl-terminal residues of eight dermorphin analogues (H-tyrosyl-D-alanyl-piperazine derivatives were used as the carboxyl-terminal residues of eight dermorphin analogues (H-tyrosyl-D-alanyl-piperazin-2-one or piperazine derivatives) whose opiate activities were examined in vitro by use of the guinea pig ileum and the mouse vas deferens assays. It was found in the guinea pig ileum assay that the configuration of pheylalanine and the replacement of the piperazin-2-one ring with a piperazine ring are important for enhancing or reducing the opiate activities of these analogues.
Yamashita
T
T
Department of Chemistry, Faculty of Science, Osaka City University, Japan.
Hatamoto
E
E
Takenaka
H
H
Kojima
Y
Y
Inoue
Y
Y
Gemba
M
M
Yasuda
M
M
D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects
D000701:Analgesics, Opioid; D009842:Oligopeptides; D010879:Piperazines