Synthesis and biological evaluation of benzoisothiazole derivatives possessing N,N-dimethylformimidamide group as 5-HT₆ receptor antagonists.

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.