Dicationic 2-fluorenonylcarbapenems: potent anti-MRS agents with improved solubility and pharmacokinetic properties.
The synthesis and biological evaluation of a series of dicationic-substituted 2-fluorenonylcarbapenems is described. This class of compounds showed enhanced water solubility while maintaining potent activity against MRS. Introduction of a 1-beta-methyl substituent was found to improve pharmacokinetics.
Greenlee
M L
ML
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Laub
J B
JB
Rouen
G P
GP
DiNinno
F
F
Hammond
M L
ML
Huber
J L
JL
Sundelof
J G
JG
Hammond
G G
GG
D000818:Animals; D015780:Carbapenems / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002412:Cations; D006207:Half-Life; D008253:Macaca mulatta; D016106:Methicillin Resistance; D051379:Mice; D008826:Microbial Sensitivity Tests; D012995:Solubility; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects*
D015780:Carbapenems; D002412:Cations