Structure-activity relationships within a series of C(7)-substitutedoxyiminocephalosporins containing the C(3)-methylaminopyridiniumthiomethyl substituent. Synthesis and biological properties of BRL 57342 and some close analogues.
(6R,7R)-7-[2-(2-Amino-4-thiazolyl)-2-[(Z)-[(S)-carboxy(3,4- dihydroxyphenyl)methyl]oxyimino]acetamido]-3-(1-methylaminopyri dinium-4-thiomethyl)ceph-3-em-4-carboxylate sodium salt (BRL 57342, 1f) combines excellent in vitro antibacterial potency against Gram-positive and Gram-negative bacteria, including P. aeruginosa and Acinetobacter spp., with excellent stability to extended spectrum beta-lactamases. This potency is reflected in in vivo efficacy studies.
Adams
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RG
SmithKline Beecham Pharmaceuticals, Research Division, Betchworth, Surrey, U.K.
Brain
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EG
Branch
C L
CL
Guest
A W
AW
Harrington
F P
FP
Mizen
L
L
Neale
J E
JE
Pearson
M J
MJ
Simpson
I N
IN
Smulders
H
H
D000818:Animals; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D012453:Saimiri; D013329:Structure-Activity Relationship
C094358:BRL 57342; D002511:Cephalosporins