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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 ophenylenediamine 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), and6o(pA2: 7.2) exhibited antagonism greater than that of the standard 5-HT3 antagonist, ondansetron (pA2: 6.9).

The condensation of o-phenylenediamines with 1,2-dicarbonyl compounds in the presence of citric acid afforded the corresponding quinoxaline derivatives in higher yields at room temperature in ethanol, and most of the reactions were completed in less than 1 min.

A series of novel 3-substituted quinoxalin-2-carboxamides were designed as per the pharmacophoric requirement for 5-HT(3) receptor antagonists and prepared by microwave irradiation and also by conventional method. The compounds were characterized by spectral data (IR, (1)H NMR, and MS) and the purity was ascertained by microanalysis. The synthesized compounds were evaluated for 5-HT(3) antagonisms in longitudinal muscle-myenteric plexus preparation from guinea pig ileum against 5-HT(3) agonist, 2-methyl-5-HT. Among the test compounds, N-{3-[(4-methylpiperazin-1-yl)methyl]-4-hydroxyphenyl}-3-methoxyquinoxalin-2-carboxamide 4e showed most favorable 5-HT(3) receptor antagonism.

Mono and bis substituted dialkylamino alkyl-p-aminophenol 3 are prepared by treating paracetamol 1 with formaldehyde and appropriate secondary amines followed by deacetylation using 6 M HCI in unmodified domestic microwave oven in unsealed borosil vessels. The compounds are obtained within a short duration of time (3 min). The rate of the reaction is found to be accelerated by about 60 fold when compared to conventional heating.