Pyrimidine and cumene derivatives functionalized by hydroxy and methoxy: Computational insights in drug-likeness, ADM, and toxicity studies

[Display omitted] •OH and –OCH3 functionalized isopropyl cumene and pyrimidine derivatives were designed.•The molecular properties and physical parameters were ChemOffice 17.0 suite.•The structural confirmation, NBO, FMO, and MEP analyses were performed by G09W.•Water solubility, lipophilicity, drug-likeness, and bioavailability were determined by SwissADME.•ADME, medicinal and environmental toxicity scores were estimated by ADMELab. The –OH and –OCH3 functionalized isopropyl cumene and isopropyl pyrimidine derivatives were designed and, explored in terms of the ADM, and possible toxic effects in view of the medicinal and environmental. For this goal, the geometry optimizations and structural confirmations were conducted by the G09W package at B3LYP/6-311G** level of theory. The verified geometries were used for further computations and analyses. The bioavailability features such as lipophilicity, water solubility, and drug-likeness, pharmacokinetics were determined by SwissADME tools. Also, ADMETLab computations were used to predict the absorption, distribution, metabolism, and toxicity of the data set. The FMO and NBO analyses were performed to determine the –OH and –OCH3 function effect on the cumene and pyridine structures and then the electronic properties underlying the bioavailability and toxicity properties. Accordingly, the –OCH3 function on the structure l seems to be important to rise the inhibitory or substrate potency in the enzyme metabolism for both series. For the pyrimidine series, the anomeric interactions (n → σ*) in addition to the resonance interactions (n → π* and π → π*) also would have a role in molecular stability and affect the charge distribution on the molecular surface, which could play of remarkable role in the bioavailability and ADM. In terms of electronic structure and physicochemical properties, and possible bioactivity or toxicity relationship, the results obtained in the study will be an important reference source for the research on exploring/developing/improving future biocompatible molecular structures.