GABA-uptake inhibitors: construction of a general pharmacophore model and successful prediction of a new representative

V N'Goka, G Schlewer, JM Linget…

Index: N'Goka; Schlewer; Linget; Chambon; Wermuth Journal of Medicinal Chemistry, 1991 , vol. 34, # 8 p. 2547 - 2557

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Citation Number: 68

Abstract

A model fcir the pharmacophore of GABA-uptake inhibitors was established using published structureactivity data and molecular modeling. The model accounted for the activities of different classes of GABA-uptake inhibitors. Analogues of guvacine substituted at position 6 were synthesized in order to confirm the model. 6-(3, 3-Diphenylpropy1) guvacine (300, which fit well with the pharmacophore, had an in vitro ICm of 0.1 pM. This value is as good ...