Design, Synthesis and Evaluation of Antidepressant Activity of Novel 2‐Methoxy 1, 8 Naphthyridine 3‐Carboxamides as 5‐HT3 Receptor Antagonists. (14th March 2014)

• Record Type: Journal Article
• Authors: Mahesh, Radhakrishnan; Dhar, Arghya Kusum; Jindal, Ankur; Bhatt, Shvetank
• Is Part Of: Chemical biology & drug design. Volume 83:Number 5(2014:May)
• Page Start: 583
• Page End: 591
• Publication Date: 2014-03-14
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12271
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12271-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A series of novel 1, 8‐naphthyridine‐3‐carboxamides as 5‐HT<sub>3</sub> receptor antagonists were synthesized with an intention to explore the antidepressant activity of these compounds. The title carboxamides were designed using ligand‐based approach keeping in consideration the structural requirement of the pharmacophore of 5‐HT<sub>3</sub> receptor antagonists. The compounds were synthesized using appropriate synthetic route from the starting material nicotinamide. 5‐HT<sub>3</sub> receptor antagonism of all the compounds, which was denoted in the form of p<italic>A</italic><sub>2</sub> value, was determined in longitudinal muscle myenteric plexus preparation from guinea‐pig ileum against 5‐HT<sub>3</sub> agonist, 2‐methyl‐5‐HT. Compound <bold>8g</bold> (2‐methoxy‐1, 8‐naphthyridin‐3‐yl) (2‐methoxy phenyl piperazine‐1‐yl) methanone was identified as the most active compound, which expressed a p<italic>A</italic><sub>2</sub> value of 7.67. The antidepressant activity of all the compounds was examined in mice model of forced swim test (FST); importantly, none of the compounds was found to cause any significant changes in the locomotor activity of mice at the tested dose levels. In FST, the compounds with considerably higher p<italic>A</italic><sub>2</sub> value exhibited promising antidepressant‐like activity, whereas compounds with lower p<italic>A</italic><sub>2</sub> value did not show antidepressant‐like activity as compared to the control group.</p> </abstract>