Synthesis and biological evaluation of benzoisothiazole derivatives possessing N,N-dimethylformimidamide group as 5-HT 6 receptor antagonists

Abstract

A series of novel N,N-dimethyl-N′-(5-(Ar-sulfonamido) benzo[d]isothiazol-3-yl)formimidamides was designed and synthesized as 5-HT 6 ligands. Here N,N-dimethyl formimidamides was used as a replacement for an aminoethyl moiety. In vitro functional assays demonstrated compounds 9b and 9i significantly inhibited the 5-HT-induced Ca 2+ increases (9b; IC 50 = 0.36 μM and 9i; IC 50 = 0.44 μM), indicating that 9b and 9i were potent 5-HT 6 receptor antagonists. Compounds 9i also showed good selectivity on the 5-HT 6 over 5-HT 4 and 5-HT 7 receptors. © 2012 Published by Elsevier Ltd. All rights reserved.