Chemoenzymatic synthesis and binding affinity of novel ( R)- and ( S)-3-aminomethyl-1-tetralones, potential atypical antipsychotics

A series of ( R)- and ( S)-3-aminomethyl-1-tetralones, conformationally constrained analogues of haloperidol, have been obtained by enzymatic resolution of the corresponding racemic 3-hydroxymethyl-1-tetralones using Pseudomonas fluorescens lipase. Their binding affinities at dopamine D 2 and serotonin 5-HT 2A and 5-HT 2C receptors were determined showing in some cases an atypical antipsychotic profile with Meltzer's ratio higher than 1.30. The chemoenzymatic preparation and the binding affinities of new ( R)- and ( S)-3-aminomethyl-1-tetralones is described. Some of these compounds [e.g., ( S)-(+)- 8d] showed potential atypical antipsychotic profiles with Meltzer's ratio higher than 1:30.