Synthesis and SAR of novel oxazolidinones: discovery of ranbezolid.
Novel oxazolidinones were synthesized containing a number of substituted five-membered heterocycles attached to the 'piperazinyl-phenyl-oxazolidinone' core of eperezolid. Further, the piperazine ring of the core was replaced by other diamino-heterocycles. These modifications led to several compounds with potent activity against a spectrum of resistant and susceptible gram-positive organisms, along with the identification of ranbezolid (RBx 7644) as a clinical candidate.
Das
Biswajit
B
Department of Medicinal Chemistry, Ranbaxy Research Laboratory, Plot-20, Sector-18, Udyog Vihar, Gurgaon 122001, India. biswajit.das@ranbaxy.com
Rudra
Sonali
S
Yadav
Ajay
A
Ray
Abhijit
A
Rao
A V S Raja
AV
Srinivas
A S S V
AS
Soni
Ajay
A
Saini
Suman
S
Shukla
Shalini
S
Pandya
Manisha
M
Bhateja
Pragya
P
Malhotra
Sunita
S
Mathur
Tarun
T
Arora
S K
SK
Rattan
Ashok
A
Mehta
Anita
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006571:Heterocyclic Compounds; D051379:Mice; D008826:Microbial Sensitivity Tests; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D005663:Furans; D006571:Heterocyclic Compounds; D010080:Oxazoles; D023303:Oxazolidinones; C476340:ranbezolid