Ligand-Based Design, Synthesis, and Pharmacological Evaluation of 3-Methoxyquinoxalin-2-carboxamides as Structurally Novel Serotonin Type-3 Receptor Antagonists

Abstract

Employing a ligand-based approach, 3-methoxyquinoxalin-2-carboxamides were designed as serotonin type-3 (5-HT3) 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-HT3 receptor antagonisms in longitudinal muscle myenteric plexus preparations from guinea-pig ileum against a standard 5-HT3 agonist, 2-methy-5-HT, and their antagonism activities are expressed as pA2 values. Compounds 6a (pA2: 7.2), 6e (pA2: 7.0), 6f (pA2: 7.5), 6g (pA2: 7.5), 6n (pA2: 7.0), and 6o (pA2: 7.2) exhibited antagonism greater than that of the standard 5-HT3 antagonist, ondansetron (pA2: 6.9).