Synthesis and biological activity of novel 3-(2-propenyl)-cephalosporins. II. Preparation of prodrugs.
Three prodrug esters (2a approximately 2c) of 3-(2-propenyl)cephem (1a) have been prepared and their oral absorption was determined in rats and mice. While pivaloyloxymethyl ester (2a) did not improve the oral absorption of the parent cephem 1a, [(1-methyl)ethoxycarbonyloxy]ethyl ester (2b) and (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester (2c) improved oral absorption by a factor of five.
Kim
W J
WJ
Korea Research Institute of Chemical Technology, Daedeog-Danji, Daejeon.
Ko
K Y
KY
Jung
M H
MH
Kim
M
M
Lee
K I
KI
Kim
J H
JH
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002511:Cephalosporins / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*
D002511:Cephalosporins; D011355:Prodrugs; D013844:Thiazoles; C071796:pivaloyloxymethyl 7-(2-(2-amino-4-thiazole)-2-methoxyiminoacetamido)-3-(2-propenyl)-3-cephem-4-carboxylate; C071797:((1-methyl)ethoxycarbonyloxy)-ethyl 7-(2-(2-amino-4-thiazole)-2-methoxyaminoacetamido)-3-(2-propenyl)-3-cephem-4-carboxylate; C071798:(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 7-(2-(2-amino-4-thiazole)-2-methoxyiminoacetamido)-3-(2-propenyl)-3-cephem-4-carboxylate