Analogues of the potential antipsychotic agent 1192U90: amide modifications Original Research Article

Analogues of 2-amino-N-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)-butyl)benzamide hydrochloride (1192U90) were prepared and evaluated in receptor binding assays for the dopamine D2, serotonin 5-HT1a, and serotonin 5-HT2 receptors. Eight compounds have been synthesized in which the amide group of 1192U90 has been replaced with a variety of functional groups (i.e. ester, ketone, thioamide, butyramide, butyranilide, sulfonamide, alkoxyamide and hydrazide). These compounds exhibited moderate to potent affinities (0.55–200 nM) for all three receptors. Several analogues exhibited improved selectivity for the 5-HT2 receptor with D2/5-HT2 binding ratios greater than 1192U90.