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

Design, synthesis, and preliminaryin vitroandin vivopharmacological evaluation of 2-{4-[4-(2,5-disubstituted thiazol-4-yl)phenylethyl]piperazin-1-yl}-1,8-naphthyridine-3-carbonitriles as atypical antipsychotic agents

“…22 2-(Piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile was also prepared as defined using microwave irradiation technique. 21 Equimolar amounts of 2-(piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile (9) and 2-and 5-substituted chloroethylphenylthiazoles (17) along with 2.125 equivalents of anhydrous Na 2 CO 3 and catalytic amount of KI (2 mg) in DMF as solvent when refluxed for 48 h afforded the title compounds. All the synthesized compounds were characterized by spectral (IR, 1 H NMR, and MS) and elemental analysis data.…”

“…21,22 All other starting materials and solvents were obtained from commercially available sources and used without additional purification.…”

“…Using this strategy, the current marketed drug ziprasidone was developed. 19 We adopted this strategy and employed 2-(piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile, which has affinity towards serotonin receptors 21 as one portion of the molecule and chloroethylphenylthiazoles was selected as other portion as Pfizer group has come up with potent atypical antipsychotics using this heterocyclic system. 22 We synthesized compounds in which 2-and 5-substituted chloroethylphenylthiazoles (1-7) have been incorporated at the piperazinyl nitrogen atom of 2-(piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile looking for 5-HT 2A and D 2 antagonism.…”

“…21,23 During the experimentation, mice were placed individually in separate aluminium cages, measuring 20 × 15 × 15 cm 3 , with walls lined with 1 cm 2 aluminium wire mesh (diameter 2 mm). They were placed in the above cages 30 min for adaptation before the experiment.…”

Quinoxalin-2-carboxamides: synthesis and pharmacological evaluation as serotonin type-3 (5-HT3) receptor antagonists

“…For the study, first N-phenylpiperazine was coupled with quinoxalin-2-carboxylic acid; the obtained carboxamide 4a showed antagonism (pA 2 : 7.3) greater than standard drug, ondansetron (pA 2 : 6.9) 19 . In order to find out more potent carboxamides, an electron releasing group, a methoxy group was introduced on the phenyl group at second position; the resultant carboxamide 4b drastically lost its potency compared to compound 4a (with no substituent on the phenyl ring) and the observed pA 2 value was 4.5.…”