STRUCTURE-ACTIVITY-RELATIONSHIPS OF DERMORPHIN ANALOGS CONTAINING CHIRAL PIPERAZIN-2-ONE AND PIPERAZINE DERIVATIVES

The amide and ester carbonyl groups of four piperazin-2-one derivative s (N,N'-ethylene-bridged dipeptide ethyl esters) constructed from (R)- or (S)-phenylalanine and glycine were reduced with borane-tetrahydrof uran 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-ty rosyl-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 as say that the configuration of phenylalanine and the replacement of the piperazin-2-one ring with a piperazine ring are important for enhanci ng or reducing tile opiate activities of these analogues.