Studies on condensed-heterocyclic azolium cephalosporins. III. Synthesis and antibacterial activity of 7 beta-[2-(2-amino-5-substituted-thiazol-4-yl)-2 (Z)-alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl-3-cephem-4- carboxylates.
As a part of our research on the synthesis of cephalosporins bearing condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus, we describe herein the synthesis of 7 beta-[2-(2-amino-5-halogeno-, methylthio-, methylsulfinyl-, methylsulfonyl- and sulfothiazol-4-yl)-2(Z)-alkoxyiminoacetamido] cephalosporins and their antibacterial activity. Among the compounds prepared, 7 beta-[2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido]-3-(imidazo[1,5-a]-pyridinium-1-yl)methyl-3-cephem -4-carboxylate (14) showed good antibacterial activity against both Staphylococcus aureus including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, whereas the antibacterial activity against other Gram-negative bacteria was a slightly lower than that of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(im ida zo [1,2-a]pyridinium (I-1) and imidazo[1,5-a]pyridinium (I-4)-1-yl)methyl-3-cephem-4-carboxylates.
Nishimura
T
T
Chemistry Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Yoshimura
Y
Y
Miyake
A
A
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D015281:Cefmenoxime / Q000494:pharmacology; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D000097572:Cefpirome
D000900:Anti-Bacterial Agents; D015281:Cefmenoxime; D002511:Cephalosporins; D000097572:Cefpirome; C074827:7-(2-(2-amino-5-chlorothiazole-4-yl)-2-methoxyiminoacetamido)-3-azolium-3-cephem-4-carboxylate; C074826:7-(2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido)-3-(imidazo(1,5-a)pyridinium-2-yl)methyl-3-cephem-4-carboxylate; C074824:7-(2-(2-aminothiazolyl)-2-methoxyiminoacetamido)-3-(imidazo(1,2-a)pyridinium-1-yl)methyl-3-cephem-4-carboxylate; C074825:7-(2-(2-amino-5-chlorothiazol-4-yl)-2-methoxyiminoacetamido)-3-(imidazo(1,5-a)-pyridinium-1-yl)methyl-3-cephem-4-carboxylate