Synthesis and biological evaluation of novel imidazolone derivatives as potential COX-2 inhibitors

Abstract

Three novel series of 2-(substituted phenyl)-4-(substituted arylidene)-imidazolone-5-(4H)-ones were derived from the corresponding oxazolones by condensation with different arylamines. Eleven of the synthesized compounds were selected and evaluated for their effect on carrageenan-induced rat paw edema. Compound 4b had the same efficacy as the reference standard (indomethacin), and compounds 3b, 3c, 4a, 4d and 9a showed good to excellent activities, with other compounds only weakly active. The potent compounds were evaluated for their inhibitory activities against COX-2-catalyzed PGE(2) production, with 4a, 4b and 3c showing strong inhibitory activity.

Synthesis, Antimicrobial, Anti-Virulence and Anticancer Evaluation of New 5(4H)-Oxazolone-Based Sulfonamides

“…The exocyclic double bond in position four of the oxazolone ring provides a new reactivity that allows the construction of interesting derivatives [10]. Moreover, 2-phenyloxazol-5(4H)-ones with an additional exocyclic double bond exhibits a wide range of biological activities such as antibacterial [11], immunomodulatory [10,12,13], antidiabetic [14], antiviral [15], antifungal [16], anticancer [17], anti-inflammatory [18], anti-HIV [19], anti-angiogenic [20], sedative [21], and tyrosinase inhibitory activities [22], among others (Figure 1). Notably, there are numerous drugs containing oxazolone motif in their structure such as the carbonate codrug, CB-NTXOL-BUPOH (I), consisting of 6-β-naltrexol (the major active metabolite of naltrexone, a potent µ-opioid receptor antagonist used in the treatment of alcohol dependence and opioid abuse) covalently linked by carbonate ester linkage to a modified form of hydroxybupropion (bupropion with oxazolone) [23].…”

Silica‐supported Solvent Approaches More Facile than the Conventional for Erlenmeyer Synthesis with Our Pyridinium Salts

“…Applications of oxazolone derivatives are extended owing to the presence of an exocyclic double bond at 4‐position, which gives some useful and interesting pharmaceutical drugs like immunomodulatory , anti‐inflammatory , antifungal , and antibacterial purpose. Greener approach is the construction of chemical compounds and processes that eliminate or minimize the generation and usage of environmental‐polluting substances .…”

2-Phenyl-4-bis(methylthio)methyleneoxazol-5-one: versatile template for diversity oriented synthesis of heterocycles

“…1d Thus, compounds containing the imidazol-5-(4H)one core are associated with antiviral (against both HSV and HIV), 1d anticonvulsant, 3 immunosupressant, 4 protein kinase C (CDK-4) inhibitor, 1a inflammation mediator, 1b fungicidal and herbicidal 1d and COX-2 inhibitor activity. 5 Some of these compounds act as antagonists against various receptors 6 such as angiotensin II receptor, dopamine CGRP, b 3 -adrenergic and GABAA receptors. 6 Similarly, aplysinopsin, a naturally occurring 4-(indolylmethylene)-5-imidazolone derivative and its analogs display specific cytotoxicity for cancer cells, 7a-c antileishmanial 7d and anti-infective 7e activity, and affect neurotransmission.…”