Synthesis and structure activity relationship studies of 2-amino-4-arylysulfonyl-5,6,7,8-tetrahydroquinazolines as 5-HT6 receptor antagonists

Abstract

A novel series of 4-arylthio- or 4-arylsulfonyl-substituted 2-amino-5,6,7,8-tetrahydroquiazolines was synthesized and evaluated for serotonin receptor subtype 6 (5-HT6R) antagonistic effects in vitro. The structure activity relationships (SAR) of this series were discussed on the basis of in vitro activity. Among the derivatives synthesized in the present study, the lead compound, 7a, having sulfonyl functionality at the 4-position and N-methylpiperazine at the 2-position of the core structure showed the most potent 5-HT6 receptor inhibitory activity in vitro and good metabolic stability without CYP liability.