Microwave assisted synthesis of 2-(4-substituted piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile as a new class of serotonin 5-HT3 receptor antagonists.
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.
Mahesh
Radhakrishnan
R
Pharmacy Group, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India. rmahesh@bits-pilani.ac.in
Perumal
Ramachandran Venkatesha
RV
Pandi
Pandi Vijaya
PV
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008872:Microwaves; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000294:innervation; D009197:Myenteric Plexus / Q000502:physiology; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
C498374:2-(4-allylpiperazin-1-yl)-1,8-naphthyridine-3-carbonitrile; D009287:Naphthyridines; D009570:Nitriles; D010879:Piperazines; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists