Synthesis and in vitro antibacterial activities of 3-thiazol-4-yl-1-carba-1-dethiacephalosporins.
The synthesis and microbiological evaluation of a new series of 3-thiazol-4-yl-carba-1-dethiacephalosporins is described. Structure activity relationship was achieved by changing substitution at the 2-position of the thiazole moiety. The result was a marked variance of microbiological activity in the C7 side-chain derivatives. ATMO derivatives possess potent activity against both Gram-positive and Gram-negative bacteria. For example, MICs (microgram/ml) of LY215226 against representative organisms are as follows: S. aureus 0.25, S. pneumoniae 0.008, H. influenzae 0.008, E. coli 0.25, K. pneumoniae 0.008, E. cloacae 0.5, S. typhi 0.25, and M. morganii 0.25.
Hornback
W J
WJ
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Munroe
J E
JE
Counter
F T
FT
D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016972:Enterobacter cloacae / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006193:Haemophilus influenzae / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C089904:7-((2-aminothiazol--4-yl)methoximinoacetylamino)-1-carba(1-dethia)-3-(2-aminothiazol-4-yl)-3-cephem-4-carboxylic acid; C089901:7-((2-aminothiazol-4-yl)-4--methoximinoacetylamino)-1-carba(1-dethia)-3-(2-(5-nitrothiazol-2-yl)thiazol-4-yl)-3-cephem-4-carboxylic acid; C089903:7-((2-aminothiazol-4-yl)-methoximinoacetylamino)-1-carba(1-dethia)-3-(2-((phenyl)(2-pyridyl)methyl)thiazol-4-yl)-3-cephem-4-carboxylic acid; C089900:7-((2-aminothiazol-4-yl)methoximinoacetylamino)-1-carba(1-dethia)-3-(2-phenylthiazol-4-yl)-3-cephem-4-carboxylic acid; C089902:7--((2-aminothiazol-4-yl)methoximinoacetylamino)-1-carba(1-dethia)-3-(2-(1-methyl-3-pyridyl)thiazol-4-yl)-3-cephem-4-carboxylic acid; D002511:Cephalosporins; D013844:Thiazoles