Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors.
Bioorg Med Chem Lett
; 18(16): 4521-4, 2008 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-18662877
ABSTRACT
Three new types of aryl diketo acid (ADK) isosteres were designed by conversion of the biologically labile 1,3-diketo unit into heteroaromatic motif such as isoxazole, isothiazole, or 1H-pyrazole to improve the physicochemical property of ADK-based HIV-1 integrase (IN) inhibitors. The synthesis of the heteroaromatic carboxylic acids was established by employing phenyl beta-diketoester or benzaldehyde as the starting material and 1,3-dipolar cycloaddition as the key reaction. Of the compounds tested, the 3-benzyloxyphenyl-substituted isoxazole carboxylic acid displayed the best IN inhibitory and antiviral activities, with N-hydroxylamidation enhancing the in vitro and in vivo potency. These findings are important for further optimization of ADK-based IN inhibitors.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ácidos Carboxílicos
/
Infecciones por VIH
/
Química Farmacéutica
/
VIH-1
/
Inhibidores de Integrasa VIH
/
Fármacos Anti-VIH
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2008
Tipo del documento:
Article
País de afiliación:
China