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 e!ciently. Such conjugates show improved solubility and permeability properties compared with the bare sca"old 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.

READ FULL ARTICLE HERE: https://pubs.acs.org/doi/10.1021/acsmedchemlett.2c00476

PUBLICATION: Achyutharao Sidduri, Mark J. Dresel, and Spencer Knapp, ACS Med. Chem. Lett. 2023, 14, 2, 176–182