ABSTRACT
A series of novel 2-(4-substituted piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile 6 were prepared by microwave irradiation and conventional heating. The intermediate, 2-oxo-1,2-dihydro-1,8-naphthyridine-3-carbonitrile 3, was prepared from 2-aminonicotinaldehyde 1 and ethyl cyanoacetate 2 in the presence of piperidine under solvent free condition. The synthesized compounds were evaluated for 5-HT3 antagonisms in longitudinal muscle-myenteric plexus (LMMP) preparation from Guinea pig ileum against 5-HT3 agonist, 2-methyl-5-HT. Among the compounds tested, 2-(4-allylpiperazin-1-yl)-1,8-naphthyridine-3-carbonitrile 6d showed most favorable 5-HT3 receptor antagonism in the Guinea pig ileum.
Subject(s)
Naphthyridines/chemical synthesis , Nitriles/chemical synthesis , Piperazines/chemical synthesis , Serotonin 5-HT3 Receptor Antagonists , Serotonin Antagonists/chemical synthesis , Animals , Guinea Pigs , Ileum/drug effects , Ileum/innervation , Ileum/physiology , In Vitro Techniques , Male , Microwaves , Muscle Contraction/drug effects , Muscle, Smooth/innervation , Myenteric Plexus/physiology , Naphthyridines/chemistry , Naphthyridines/pharmacology , Neuromuscular Junction/drug effects , Neuromuscular Junction/physiology , Nitriles/chemistry , Nitriles/pharmacology , Piperazines/chemistry , Piperazines/pharmacology , Receptors, Serotonin, 5-HT3/physiology , Serotonin Antagonists/chemistry , Serotonin Antagonists/pharmacology , Structure-Activity RelationshipABSTRACT
A series of 3-chloroquinoxaline-2-carboxamides were designed and prepared by the condensation of 3-chloro-2-quinoxaloylchloride with appropriate Mannich bases of the p-aminophenol in the microwave environment. The synthesized compounds were evaluated for serotonin(3) (5-HT(3)) receptor antagonistic activities in longitudinal muscle-myenteric plexus (LMMP) preparation from guinea pig ileum against the 5-HT(3) agonist, 2-methyl-5-HT. Compound 3g exhibited comparable 5-HT(3) antagonistic activity (pA(2) 6.4) to that of standard antagonist Ondansetron (pA(2) 6.9), while the other compounds exhibited mild to moderate 5-HT(3) antagonistic activities.