Design, Synthesis and Evaluation of Antidepressant Activity of Novel 2‐Methoxy 1, 8 Naphthyridine 3‐Carboxamides as 5‐HT₃ Receptor Antagonists

Abstract

A series of novel 1,8-naphthyridine-3-carboxamides as 5-HT3 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-HT3 receptor antagonists. The compounds were synthesized using appropriate synthetic route from the starting material nicotinamide. 5-HT3 receptor antagonism of all the compounds, which was denoted in the form of pA2 value, was determined in longitudinal muscle myenteric plexus preparation from guinea-pig ileum against 5-HT3 agonist, 2-methyl-5-HT. Compound 8g (2-methoxy-1, 8-naphthyridin-3-yl) (2-methoxy phenyl piperazine-1-yl) methanone was identified as the most active compound, which expressed a pA2 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 pA2 value exhibited promising antidepressant-like activity, whereas compounds with lower pA2 value did not show antidepressant-like activity as compared to the control group.

Practical Synthesis, Antidepressant, and Anticonvulsant Activity of 3‐Phenyliminoindolin‐2‐one Derivatives

“…A metabolic disorder of monoamine neurotransmitters is believed to be the main biochemical cause of depression in the CNS. Depression can be alleviated by increasing the levels of monoamine neurotransmitters in the CNS (29)(30)(31)(32). Compound 3r significantly increased 5-HT and NE levels in mouse brain in the FST, similar to the positive control drug FLU.…”

Design, Synthesis, and Potential Antidepressant‐like Activity of 7‐prenyloxy‐2,3‐dihydroflavanone Derivatives

“…The intermediates 2a – 2n were synthesized by the Claisen–Schmidt condensation of compound 1 protected as methoxymethyl ether with substituted aromatic aldehydes . Then, the intermediates 2a – 2n were treated with 3M HCl in methanol to yield the hydroxychalcones 3a – 3n . The latter compounds subsequently underwent a substitution reaction with prenyl bromide in acetone under reflux to give compounds 4a – 4n .…”

“…The target compounds synthesized in this study were screened for their antidepressant‐like activities using Porsolt's behavioral despair (forced swimming test) . Compounds 5j and 5k were also evaluated using the tail suspension test and the open‐field test to further confirm its antidepressant activity. The tested compounds in the pharmacology experiments were dissolved in DMSO, and administrated intraperitoneally ( i.p .)…”

Synthesis and Antibacterial Activity of Novel 5-Arylidene-2-Imino-3-(2- Phenyl- 1,8-Naphthyridin-3-Yl)thiazolidin-4-Ones

“…Among the different classes of heterocyclic units, the 1,8-naphthyridine unit is a privileged scaffold and widely distributed in many biologically active synthetic compounds [2]. 1,8-naphthyridine and its derivatives possess valuable pharmacological applications including antibacterial [3], antidepressant [4], antitubercular [5], anticancer [6], antihypertensive [7], and antiplatelet [8] activities. Similarly, thiazolidin-4-one and its 5-arylidene derivatives are represented as an interesting class of molecules showing a broad-spectrum of medical applications such as antimicrobial [9], anti-inflammatory [10], DPPH radical scavenger [11], antifungal [12], anticancer [13], and anticonvulsant [14] activities.…”