Incorporation of an Isohexide Subunit Improves the Drug-like Properties of Bioactive Compounds.
ACS Med Chem Lett
; 14(2): 176-182, 2023 Feb 09.
Article
em En
| MEDLINE
| ID: mdl-36793427
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.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos