Ligand-based design, synthesis, and pharmacological evaluation of 3-Methoxyquinoxalin-2-carboxamides as structurally novel serotonin type-3 receptor antagonists.

Employing a ligand-based approach, 3-methoxyquinoxalin-2-carboxamides were designed as serotonin type-3 (5-HT(3) ) receptor antagonists and synthesized from the starting material o-phenylenediamine in a sequence of reactions. The structures of the synthesized compounds were confirmed by spectral data. These carboxamides were investigated for their 5-HT(3) receptor antagonisms in longitudinal muscle myenteric plexus preparations from guinea-pig ileum against a standard 5-HT(3) agonist, 2-methy-5-HT, and their antagonism activities are expressed as pA(2) values. Compounds 6a (pA(2) : 7.2), 6e (pA(2) : 7.0), 6f (pA(2) : 7.5), 6g (pA(2) : 7.5), 6n (pA(2) : 7.0), and 6o (pA(2) : 7.2) exhibited antagonism greater than that of the standard 5-HT(3) antagonist, ondansetron (pA(2) : 6.9).