Work

Incorporation of an Isohexide Subunit Improves the Drug-like Properties of Bioactive Compounds

Year: 2023

Type: article

Abstract: An enhanced ability to pre-engineer favorable drug-likeness qualities into bioactive molecules would focus and streamline the drug development process. We find that phenols, carboxylic acids, and a purine react with isosorbide ("GRAS" designated) under Mitsunobu coupling conditions to deliver the isoidide conjugates selectively and efficiently. Such conjugates show improved solubility and permeability properties compared with the bare scaffold compounds themselves, and the purine adduct may have applications as a 2'-deoxyadenosine isostere. We anticipate additional benefits, implied by their structures, in metabolic stability and reduced toxicity of the isoidide conjugates as well.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.2c00476

Authors: Achyutharao Sidduri, Mark J. Dresel, Spencer Knapp

Institution: Rutgers, The State University of New Jersey

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

Open Access status: green

Funders: Rutgers, The State University of New Jersey, National Institutes of Health, National Heart, Lung, and Blood Institute

Award: Rutgers Optimizes Innovation (ROI) Program