Orally active cephalosporins. Part 2: synthesis, structure-activity relationships and oral absorption of cephalosporins having a C-3 pyridyl side chain.
A series of 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamid o]cephalosporins having a pyridine ring connected through various spacer moieties at the C-3 position was designed and synthesized and evaluated for antibacterial activity and oral absorption in rats. All compounds showed potent antibacterial activity against Staphylococcus aureus, whereas antibacterial activity against gram-negative bacteria was markedly influenced by the spacer moiety between the pyridine and cephem nucleus. Oral absorption was influenced by the position of the pyridine nitrogen as well as by the spacer moiety. Among these compounds, FR86830 (14), having a 4-pyridylmethylthio moiety at the C-3 position, showed the most well balanced activity and moderate oral absorption.
Yamamoto
H
H
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, Osaka, Japan.
Terasawa
T
T
Nakamura
A
A
Kawabata
K
K
Sakane
K
K
Matsumoto
S
S
Matsumoto
Y
Y
Tawara
S
S
D000284:Administration, Oral; D000818:Animals; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D051381:Rats; D013329:Structure-Activity Relationship
D002511:Cephalosporins