Heterocyclic pharmacochemistry of new rhinovirus antiviral agents: a combined computational and experimental study

Rhinovirus (RV)​, member of the Enterovirus genus, is known to be involved in more than half of the common colds. Through advances in mol. biol., rhinoviruses have also been assocd. with exacerbations of chronic pulmonary diseases (e.g., asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis)​. In the current investigation, the authors develop a novel series of 4,​5-​dimethoxybenzyl derivs. that potently inhibits rhinovirus replication. Compd. (S)​-​7f ((S)​-​1-​(4-​(1H-​pyrazol-​4-​yl)​phenyl)​-​2-​(4,​5-​dimethoxy-​2-​nitrophenyl)​ethanol) blocks RV-​B14 replication with an EC50 value of 0.25 μM and shows a low toxicity in HeLa cells (CC50 > 271 μM)​. Enantiosepn. followed by an abs. configuration detn. by a Mosher's method revealed the interest of enantiopure compds. Mol. docking studies permitted the identification of key biol. interactions within the drug-​binding pocket and an in silico drug-​like study revealed a good potential for the development of these derivs.