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Summary Esters and amides of a series of N -acylprolyl-containing dipeptides were synthesized. It was established that these substances possess the ability to prevent memory decline evoked by maximal electroshock (MES) in a passive avoidance step-through paradigm. These N -acylprolyl-containing dipeptides were designed as analogues of pyroglutamyl-containing dipeptides, which we previously demonstrated to be highly active nootropics. Among the structure—activity relationships explored were the effect of N -acyl-substitution size, C-terminal substitution and the nature of the second amino acid. The optimal N -acyl moiety was the N -phenyl-acetyl group, while the optimal C-terminal substitution-esters were those derived from low alkyl alcohols. The optimal second amino acids were Asp, Glu or their fragments, Gly, β-Ala, GABA. Compound 1 ( N -phenylacetylprolylglycine ethyl ester) was selected for further evalution in impaired cognitive functions. It was supposed that esters and unsubstituted amides of N -acylprolylglycines are prodrugs, which convert to the bioactive cyclo-(Pro-Gly) by virtue of enzymatic or chemical lability within the body. |
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