title: Synthesis, SAR, and antibacterial activity of novel oxazolidinone analogues possessing urea functionality.
abstract: The syntheses of a number of novel oxazolidinone analogues possessing an urea functionality are reported. While the urea derivatives possessing aliphatic and aromatic groups were prepared by the more conventional isocyanate method, the derivatives possessing heterocyclic rings were synthesized by a relatively uncommon but otherwise efficient carbamate chemistry. Though the SAR resulted in novel compounds possessing in vitro activity equivalent to Linezolid, the compounds possess a range of substituents that are amenable for altering physicochemical properties of the resultant drug. The antibacterial activity was found to be not sensitive to the functional groups attached to the urea site regardless of the size and electronic characteristics. Based on in vivo results, one molecule has been identified as a candidate and additional work such as salt selection, scale-up, etc., are currently underway to take the molecule further through development.
authors.affiliation: Anti-infectives Discovery Group, Discovery Research, Dr. Reddy's Laboratories Ltd, Miyapur, Hyderabad 500 049, India. selvakumarn@drreddys.com
authors.forename: N
authors.initials: N
authors.lastname: Selvakumar
authors.forename: G Govinda
authors.initials: GG
authors.lastname: Rajulu
authors.forename: K Chandra Shekar
authors.initials: KC
authors.lastname: Reddy
authors.forename: B Chandra
authors.initials: BC
authors.lastname: Chary
authors.forename: P Kalyan
authors.initials: PK
authors.lastname: Kumar
authors.forename: T
authors.initials: T
authors.lastname: Madhavi
authors.forename: K
authors.initials: K
authors.lastname: Praveena
authors.forename: K Hari Prasada
authors.initials: KH
authors.lastname: Reddy
authors.forename: Mohammed
authors.initials: M
authors.lastname: Takhi
authors.forename: Arundhuti
authors.initials: A
authors.lastname: Mallick
authors.forename: P V S
authors.initials: PV
authors.lastname: Amarnath
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Kandepu
authors.forename: Javed
authors.initials: J
authors.lastname: Iqbal
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016984:Enterococcus faecium / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023303:Oxazolidinones