Determining the necessity of phenyl ring π-character in warfarin.
Bioorg Med Chem Lett
; 29(15): 1954-1956, 2019 08 01.
Article
em En
| MEDLINE
| ID: mdl-31147103
ABSTRACT
Despite the difficulty in administering a safe dose regimen and reports of emerging resistance, warfarin (1) remains the most widely-used oral anticoagulant for the prevention and treatment of thrombosis in humans globally. Systematic substitution of the warfarin phenyl ring with either 1,3,5,7-cyclooctatetraene (COT) (2), cubane (3), cyclohexane (4) or cyclooctane (5) and subsequent evaluation against the target enzyme, vitamin K epoxide reductase (VKOR), facilitated interrogation of both steric and electronic properties of the phenyl pharmacophore. The tolerance of VKOR to further functional group modification (carboxylate 14, PTAD adduct 15) was also investigated. The results demonstrate the importance of both annulene conferred π-interactions and ring size in the activity of warfarin.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Varfarina
/
Anticoagulantes
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article