Synthesis and SAR of novel oxazolidinones: Discovery of ranbezolid

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 19, 2005, Pages 4261-4267

  Das, Biswajit ^a   Rudra, Sonali ^a   Yadav, Ajay ^a   Ray, Abhijit ^a   Raja Rao, A V S ^a   Srinivas, A S S V ^a   Soni, Ajay ^a   Saini, Suman ^a   Shukla, Shalini ^a   Pandya, Manisha ^a   Bhateja, Pragya ^a   Malhotra, Sunita ^a   Mathur, Tarun ^a   Arora, S K ^a   Rattan, Ashok ^a   Mehta, Anita ^a  

^a Ranbaxy Reseach Laboratory   (India)

Author keywords

Antibacterial; Nitro furan derivative; Oxazolidinone; Ranbezolid; RBx 7644

Indexed keywords

OXAZOLIDINONE DERIVATIVE; RANBEZOLID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBIOTIC SENSITIVITY; ARTICLE; BACTERIAL INFECTION; CHEMICAL MODIFICATION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG RESEARCH; DRUG STRUCTURE; DRUG SYNTHESIS; GRAM POSITIVE BACTERIUM; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTI-BACTERIAL AGENTS; DRUG RESISTANCE, MICROBIAL; FURANS; GRAM-POSITIVE BACTERIA; HETEROCYCLIC COMPOUNDS; MICE; MICROBIAL SENSITIVITY TESTS; OXAZOLES; OXAZOLIDINONES; STAPHYLOCOCCAL INFECTIONS; STRUCTURE-ACTIVITY RELATIONSHIP;

POSIBACTERIA;

EID: 23944467541     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.06.063     Document Type: Article

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12. 2O: C, 50.76; H, 5.48; N, 14.09. Anal. Found: C, 50.83; H, 5.17; N, 13.83.
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17. The effect of RBx 7644 on whole cell macromolecular synthesis in anaerobes was examined recently. In each case a specific inhibitor with a known mechanism of action was included as a positive control (Trovafloxacin and Metronidazole for DNA and linezolid for protein). The results indicate that the compound is inhibitory towards protein synthesis but no effect was observed towards DNA synthesis with 1X and 4XMIC upto 6 h. However, the effect of RBx 7644 on SOS response and ability to act as a substrate for nitroreductase enzymes from Gram-negative bacteria was not investigated.
18. RBx 7644 (7) had MIC of 2 μg/mL when tested against Acr AB pump deficient and Tol C pump deficient strains, but the MIC was ≥16 μg/mL when tested against wild type Escherichia coli strains. It is possible that the excellent activity of RBx 7644 against anaerobes is because it is not effluxed out.
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