Centrally Active 2-(Substituted phenyl)-γ-aminobutyric Acids

Abstract

Alkylation of several arylmalonates with chloroalkylcyanides gave cyanoalkylmalonates (4) which were hydrogenated to aminoalkylmalonates (5). The latter were hydrolyzed to a-aryl-7-aminobutyric acids (6) which in turn were converted to ethyl esters (7). Preliminary pharmacological data demonstrate that 5, 6, and 7 are weak central stimulants.The possibility that 7-amino butyric acid (GABA) may participate in the control of neurophysiological ac-tivity1 provided a biological rationale for the synthesis of a number of its homologs and analogs for biological evaluation.2-4 The program on the synthesis of GABA homologs in these laboratories encompassed the synthesis of a-aryl-/3-alanines (1), a-aryI-7-aminobutyric acids (2), and the related esters. Our findings on the R1-R2' CHCOOH CH2NH2R+C1~R 1 R2 2 CHCOOH CH(R3)CH2NH3+Cr