Synthesis and oral activity of pivaloyloxymethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3(Z)- (4-methylthiazol-5-yl)vinyl-3-cephem-4-carboxylate (ME1207) and its related compound.
7-[2-(2-Aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3(Z)- (4-methylthiazol-5-yl)vinyl-3-cephem-4-carboxylic acid (11, ME1206) and its 3-trans isomer (13) were prepared to test antibacterial activity. These compounds exhibited excellent antibacterial activity against both gram-positive and gram-negative bacteria, including beta-lactamase producing strains. The pivaloyloxymethyl esters (12 and 14) of the compounds (11 and 13) were prepared by esterification with pivaloyloxymethyl iodide. Among them, pivaloyloxymethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]- 3(Z)-(4-methylthiazol-5-yl)vinyl-3-cephem-4-carboxylate (12, ME1207) showed good urinary recovery after oral administration in mice.
Sakagami
K
K
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Atsumi
K
K
Yamamoto
Y
Y
Tamura
A
A
Yoshida
T
T
Nishihata
K
K
Fukatsu
S
S
D000284:Administration, Oral; D000818:Animals; D002511:Cephalosporins / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests
D002511:Cephalosporins; C057710:cefditoren pivoxil