Orally active cephalosporins: synthesis, structure-activity relationships and oral absorption of 3-[(E) and (Z)-2-substituted vinyl]-cephalosporins.
Bioorg Med Chem
; 8(1): 43-54, 2000 Jan.
Article
en En
| MEDLINE
| ID: mdl-10968263
ABSTRACT
A series of 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamid o]-3-[(E)- and (Z)-2-substituted vinyl]-3-cephem-4-carboxylic acids was designed and synthesized using palladium-catalyzed coupling reactions of a 3-methanesulfonyloxy-3-cephem and an E substituted vinyl stannane or Wittig reaction of a 3-triphenylphosphoniummethyl cephem and an aldehyde as a key step. These compounds were evaluated for in vitro antibacterial activity and oral absorption in rats. A number of them exhibited excellent antibacterial activity against both gram-positive and gram-negative bacteria including Haemophilus influenzae. Among them, FR86524 (2j). having a (Z)-2-(3-pyridyl)vinyl moiety at the C-3 position, had the most well balanced activity. Although FR86254 exhibited low oral absorption, the pivaloyloxymethyl ester (23) of FR86524 showed improved oral absorption.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cefalosporinas
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2000
Tipo del documento:
Article
País de afiliación:
Japón