On the bioactive conformation of the gaba uptake inhibitor SK&F 89976-A

SK&F 89976-A (3) is a potent GABA uptake inhibitor, with a flexible diphenylbutenyl side chain. Conformationally restrained analogues of this compound, 14, 16, 18 and 20 were designed and synthesized to study the conformational preferences for binding to cloned GABA transporters. We conclude from this study that SK&F 89976-A probably binds to the GABA transporter in its fully extended conformation.