A chiral benzoquinolizine-2-carboxylic acid arginine salt active against vancomycin-resistant Staphylococcus aureus.
There is an urgent medical need for novel antibacterial agents to treat hospital infections, specially those caused by multidrug-resistant Gram-positive pathogens. The need may also be fulfilled by either exploring antibacterial agents having new mechanism of action or expanding known classes of antibacterial drugs. The paper describes a new chemical entity, compound 21, derived from hitherto little known "floxacin". The choice of the entity was made from a series of synthesized prodrugs and salts of the active chiral benzoquinolizine carboxylic acid, S-(-)-nadifloxacin. The chemistry, physicochemical characteristics, and essential bioprofile of 21 qualifies it for serious consideration as a novel drug entity against hospital infections of multi-drug-resistant Staphylococcus aureus, and its progress up to clinical phase I trials in humans is described.
de Souza
Noel J
NJ
Wockhardt Limited, Wockhardt Research Centre, D-4, MIDC, Chikalthana, Aurangabad-431 210, India.
Gupte
Shrikant V
SV
Deshpande
Prasad K
PK
Desai
Vijaya N
VN
Bhawsar
Satish B
SB
Yeole
Ravindra D
RD
Shukla
Milind C
MC
Strahilevitz
Jacob
J
Hooper
David C
DC
Bozdogan
Bülent
B
Appelbaum
Peter C
PC
Jacobs
Michael R
MR
Shetty
Nitin
N
Patel
Mahesh V
MV
Jha
Rasendrakumar
R
Khorakiwala
Habil F
HF
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D019540:Area Under Curve; D017321:Clinical Trials, Phase I as Topic; D004285:Dogs; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D024841:Fluoroquinolones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D011807:Quinolizines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D011355:Prodrugs; D011807:Quinolizines; C062127:nadifloxacin