Quantum and Classical Evaluations of Carboxylic Acid Bioisosteres: From Capped Moieties to a Drug Molecule.

ABSTRACT: Using the Quantum Theory of Atoms in Molecules, the average electron density (AED) tool was developed and employed to quantitatively evaluate the similarities between bioisosteric moieties in drug design. Bioisosteric replacements are valuable in drug molecules to fine-tune their pharmacokinetic and pharmacodynamic properties while maintaining their biological activity. This study was performed on non-classical bioisosteres of carboxylic acid. It was found that the AED of a given bioisostere is generally transferable, within less than 5% difference, irrespective of its environment. It was shown that the AED tool succeeds at depicting not only the similarities of bioisosteric groups but also at highlighting, as counter examples, the differences in non-bioisosteric groups. For the first time

SUBMITTER: Osman AMA 

PROVIDER: S-EPMC9835796 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature