New 1,3-Oxazole and 1,2,4-Oxadiazole Derivatives as Novel Agents Against Human Rhinovirus and Cytomegalovirus.

A library of 16 new five-functionalized derivatives of 2-undecyl- and 1,2,4-oxadiazole-containing 2-aryl-4-cyano-1,3-oxazoles was synthesized using α-acylamino-β,β-dichloroacrylonitriles as key building blocks, enabling efficient formation of diverse 1,3-oxazole, oxadiazole-oxazole, and sulfonamide-oxazole systems. The antiviral potential was evaluated in vitro against rhinovirus 8 (HRV8), cytomegalovirus (HCMV), parainfluenza virus type 3 (HPIV-3), and zoonotic encephalomyocarditis virus (EMCV). Screening revealed distinct activity profiles: none of the compounds inhibited EMCV or HPIV-3, while several demonstrated pronounced efficacy against HRV8 and HCMV. In concentration-dependent assays, compounds 1, 7, 10, 13, and 14 exhibited potent anti-HCMV effects (IC50 = 0.42-4.67 µM). Compound 7 showed remarkable selectivity (SI = 465), outperforming ganciclovir (GCV, SI = 326). Against HRV8, compound 2 was the most active (IC50 = 1.67 µM, SI = 11), whereas compound 13 displayed weak activity (IC50 = 21.0 µM, SI = 1). All molecules met drug-likeness criteria with favorable ADMET-predicted pharmacokinetic parameters. Molecular docking suggested that derivatives 7, 10, 13, and 14 may target viral DNA polymerase, with binding energies from -8.8 to -9.7 kcal mol-1. These findings demonstrate that 1,3-oxazoles represent a promising chemotype for new antiviral candidates active against HCMV and HRV8.