Cyclic GABA-GABOB analogues. III - Synthesis and biochemical activity of new alkyl and acyl derivatives of 4-hydroxy-2-pyrrolidinone.

The synthesis of new N-substituted 4-hydroxy (III) and 4-acyloxy- or 4-alkoxy-2-pyrrolidinones (IV), as analogues of oxiracetam (III c), is reported. For this purpose, a convenient procedure for N-alkylation of the base-labile 4-hydroxy-2-pyrrolidinones (II a, c, d) was developed. Compounds (III) and (IV) were examined on phospholipid synthesis in brain microsomal membranes of rats, both in vivo and in vivo-in vitro, and on protein synthesis in brain slices. Results showed that only oxiracetam (III c), and to a lesser extent piracetam, are active both on phospholipid and brain protein synthesis.