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.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010714:Phosphatidylethanolamines / Q000096:biosynthesis; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009419:Nerve Tissue Proteins; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011760:Pyrrolidinones