Arylpiperazine-containing pyrimidine 4-carboxamide derivatives targeting serotonin 5-HT2A, 5-HT2C, and the serotonin transporter as a potential antidepressant

Abstract

Pyrimidine usually has good pharmacokinetic properties as a drug substance and considerable efforts have been devoted to develop pyrimidine derivatives into drug candidates. Arylpiperazine-containing pyrimidine 4-carboxamide derivatives were synthesized and evaluated for binding to serotonin receptors and transporter. Pyrimidine derivatives showed good antidepressant activity in FST (forced swimming test) animal model and also displayed no appreciable inhibitory activity against hERG channel blocking assay. Herein SAR studies of pyrimidine derivatives targeting serotonin receptors and transporter will be disclosed.

Antidepressant-like activity of a new piperazine derivative of xanthone in the forced swim test in mice: The involvement of serotonergic system

“…Many research show that piperazine derivatives produce antidepressant-like activity in many behavioral tests such as FST in mice [18,19], tail suspension test in mice [20,21], and models, e.g., olfactory bulbectomised rats [22]. Similarly, some xanthone derivatives show antidepressant-like activity in various animal tests and models [5][6][7].…”

Synthesis and Evaluation of Antidepressant‐like Activity of Some 4‐Substituted 1‐(2‐methoxyphenyl)Piperazine Derivatives

“…None of the compounds affected locomotor activity in mice at the doses active in TST, and this fact suggests that the observed antidepressant-like effect was specific. It has been shown that arylpiperazines produce antidepressant-like activity in many behavioral tests and models of depression (17)(18)(19)(20)(21). The research results are convergent with our findings.…”

Piperazine scaffold: A remarkable tool in generation of diverse pharmacological agents

“…Amongst several piperazine analogues developed by Paluchowska et al, compound 103 displayed maximum antidepressant activity, higher than the reference, imipramine [184]. Amongst the various compounds synthesized by Kim et al, compound 104 emerged as a lead antidepressant agent [185]. In a series of compounds synthesized by Leslie et al, compound 105 emerged as the most potential candidate for antidepressant activity [186].…”