Microwave Synthesized Hydrophilic 4‐Oxo‐2‐phenylquinazoline‐3(4H)–carboximidamide and –Carboxamide as Privileged Small Molecule Scaffolds with Anti‐HIV‐1 Activities

Abstract

Opportunistic infections like tuberculosis (TB) are prevalent in HIV‐infected individuals. In an approach to introducing an industrial‐scale microwave‐assisted production of agents having both antiviral and antibacterial properties, a set of hydrophilic 2,3‐substituted quinazolinones, 4‐oxo‐2‐phenylquinazoline‐3(4H)‐carboximidamide (Qg) and 4‐oxo‐2‐phenylquinazoline‐3(4H)‐carboxamide (Qu), were afforded in encouraging yields. They were obtained by treating 2‐benzamidobenzoyl chloride with guanidine hydrochloride or urea in the presence of potassium carbonate in DMF. DFT calculations were employed for geometrical optimization and vibrational frequency analysis of the compounds. Free energies of solvation (ΔGsol) of Qg, and Qu calculated using DFT lend evidence in support of their hydrophilicity The anti‐HIV‐1 activities of the small‐molecule quinazolinone derivatives Qg and Qu were investigated. The synthons under in vitro conditions inhibit the entry of HIV in receptor cells with low cytotoxicity (EC50=50.53 nM for Qu and EC50=97.92 nM for Qg). The study identifies the antiviral properties of the two benzo‐fused pyrimidine derivatives, which were earlier reported to have antitubercular activity. Our findings indicate the scope for further synthetic explorations of these quinazolinone scaffolds that can lead to developing promising alternatives in drug design, pharmaceutics, and clinical research.