SYNTHESIS AND ANTIAMNESIC ACTIVITY OF A SERIES OF N-ACYLPROLYL-CONTAINING DIPEPTIDES

Eaters and amides of a series of N-acylprolyl-containing dipeptides we re synthesized. It was established that these substances possess the a bility to prevent memory decline evoked by maximal electroshock (MES) in a passive avoidance step-through paradigm. These N-acylprolyl-conta ining dipeptides were designed as analogues of pyroglutamyl-containing dipeptides, which we previously demonstrated to be highly active noot ropics. Among the structure-activity relationships explored were the e ffect of N-acyl-substitution size, C-terminal substitution and the nat ure of the second amino acid. The optimal N-acyl moiety was the N-phen yl-acetyl group, while the optimal C-terminal substitution-eaters were those derived from low alkyl alcohols. The optimal second amino acids were Asp, Glu or their fragments, Gly, beta-Ala, GABA. Compound 1 (N- phenylacetylprolylglycine ethyl ester) was selected for further evalua tion in impaired cognitive functions. It was supposed that eaters and unsubstituted amides of N-acylprolylglycines are prodrugs,which conver t to the bioactive cyclo-(Pro-Gly) by virtue of enzymatic or chemical lability within the body.