Synthesis and Central Nervous System Depressant Activity of Amino Acid Derivatives of 2- Aryl- 3- Substituted Indolizines

Gladsy Joy and Amit Kumar Das*

Department of Pharmaceutical Chemistry, Krupanidhi College of Pharmacy, Bangalore - 560 034 (India)

A series of derivatives of N-substituted-3- (2-phenylindolizinyl) propanamides (3a-j) were synthesized by condensation of methyl-3- (2-phenylindolizinyl) propanoates with various amino acids like glycine, isoleucine, glutamic acid, phenylalanine, valine and leucine using Schotten-Baumann reaction. The intermediate, methyl-3- (2-phenylindolizinyl) propanoates were prepared by condensation of methylacrylate with 2-phenylindolizines, prepared from a-picoline and a-bromoacetophenones by Tschischibabin reaction. All these derivatives were evaluated for their CNS depressant activity by Rotarod method. Out of all, compounds, 3a, 3c, 3d, 3g & 3h have shown significant and comparable CNS depressant activity to standard drug, diazepam and 3e & 3j were moderately active and remaining compounds were found inactive.

Indolizine; CNS depressant activity; amino acids