Navas F, Tang F L, Schaller L T, Norman M H
Division of Chemistry, Glaxo Wellcome Inc., North Carolina 27709, USA.
Bioorg Med Chem. 1998 Jun;6(6):811-23. doi: 10.1016/s0968-0896(98)00041-8.
Analogues of 2-amino-N-(4-(4-(1,2-benzisothiazol-3-yl)-l-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.
