Synthesis and biological activity of novel cephalosporins containing a (Z)-vinyl dimethylphosphonate group.
A series of cephalosporins containing a novel 7-[2-(Z)-(2-amino-thiazol-4- yl)-3-(dimethoxy-phosphoryl)-acryloylamino] group were prepared and their antibacterial activity measured against a range of pathogens. In general the compounds displayed a broad spectrum of activity against both Gram positive and Gram negative organisms, except Pseudomonas aeruginosa. Activity against the latter could be achieved by introducing a catechol moiety at the 3 position of the cephalosporin. The methyl phosphonates in general were stable to a wide range of beta-lactamases, including the TEM enzymes and the Enterobacter cloacae P99 chromosomal enzyme. In addition, they showed the advantage of being highly water soluble.
Smith
P W
PW
Department of Medicinal Chemistry, Glaxo Research & Development Limited, Greenford, Middlesex, UK.
Chamiec
A J
AJ
Chung
G
G
Cobley
K N
KN
Duncan
K
K
Howes
P D
PD
Whittington
A R
AR
Wood
M R
MR
D000818:Animals; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008826:Microbial Sensitivity Tests; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy; D014753:Vinyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology
D002511:Cephalosporins; D063065:Organophosphonates; D014753:Vinyl Compounds