Studies on orally active cephalosporins. I. Synthesis and structure-activity relationships of new 3-substituted carbamoyloxymethyl cephalosporins.
The synthesis and antibacterial activities of 7 beta-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-N,N - dimethylcarbamoyloxymethyl-3-cephem-4-carboxylic acid (E1100) and its analogs are described, as well as oral absorbability and in vivo activities of the 1-(isopropoxycarbonyloxy)ethyl ester (E1101) and its analogous esters. The introduction of acyclic and cyclic lower alkyl groups at the N-position of 3-carbamoyloxymethyl cephems influences antibacterial activities, especially against H. influenzae, and oral absorbability of their prodrug esters. The structure-activity relationships are also discussed.
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
S
S
Negi
M
M
Yamanaka
I
I
Sugiyama
Y
Y
Komatsu
M
M
Sasho
A
A
Tsuruoka
A
A
Kamada
I
I
Tsukada
R
R
Hiruma
K
K
Katsu
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002511:Cephalosporins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D002511:Cephalosporins