ANALOGS OF THE POTENTIAL ANTIPSYCHOTIC AGENT 1192U90 - AMIDE MODIFICATIONS

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 D-2, serotonin 5-HT1a, and serotonin 5-HT2 receptors. Eight compounds have been synthesized in w hich the amide group of 1192U90 has been replaced with a variety of fu nctional groups (i.e, ester, ketone, thioamide, butyramide, butyranili de, 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 recepto r with D-2/5-HT2 binding ratios greater than 1192U90. (C) 1998 Elsevie r Science Ltd. All rights reserved.