Synthesis and biological evaluation of 1,1-difluoro-2-(tetrahydro-3-furanyl)ethylphosphonic acids possessing a N9-purinylmethyl functional group at the ring. a new class of inhibitors for purine nucleoside phosphorylases.
Bioorg Med Chem Lett
; 9(19): 2833-6, 1999 Oct 04.
Article
en En
| MEDLINE
| ID: mdl-10522701
1,1-Difluoro-2-(tetrahydro-3-furanyl)ethylphosphonic acids cis-3 and trans-3 possessing a N9-purinylmethyl functionality at the ring were synthesized and tested as "multi-substrate analogue" inhibitors for purine nucleoside phosphorylases. Radical cyclization of allyic alpha,alpha-difluorophosphonate (E)-7 was applied to construct the alpha,alpha-difluorophosphonate-functionalized tetrahydrofuranyl moiety. The IC50 values of cis-3 and trans-3 for human erythrocyte PNP-catalyzed phosphorylation of inosine were determined to be 88 and 320 nM, respectively. The stereochemistry of the inhibitors was found to affect significantly the inhibitory potency.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Purinas
/
Purina-Nucleósido Fosforilasa
/
Compuestos de Flúor
/
Organofosfonatos
/
Furanos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
1999
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido