title: Synthesis of novel tricyclic oxazolidinones by a tandem SN2 and SNAr reaction: SAR studies on conformationally constrained analogues of Linezolid.
abstract: A series of conformationally constrained analogues of Linezolid were synthesised by employing a tandem SN(2) and SNAr reaction as the key step and tested for antibacterial activity. While the hexahydroazolo-quinoxaline compounds were inactive, the tetrahydroazolo-benzothiazine compounds exhibited interesting antibacterial activity. The introduction of fluorine in the aromatic ring further made the compounds more potent in acetamide compounds resulting in an interesting analogue 32. However, the introduction of fluorine (analogue 34) on the already potent non-fluorine thiocarbamate 21 did not have any influence on the activity.
authors.affiliation: Anti-infectives Discovery Group, Discovery Research, Dr. Reddy's Laboratories Ltd, Miyapur, Hyderabad, India. selvakumarn@drreddys.com
authors.forename: N
authors.initials: N
authors.lastname: Selvakumar
authors.forename: B
authors.initials: B
authors.lastname: Yadi Reddy
authors.forename: G
authors.initials: G
authors.lastname: Sunil Kumar
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Khera
authors.forename: D
authors.initials: D
authors.lastname: Srinivas
authors.forename: M
authors.initials: M
authors.lastname: Sitaram Kumar
authors.forename: Jagattaran
authors.initials: J
authors.lastname: Das
authors.forename: Javed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Sanjay
authors.initials: S
authors.lastname: Trehan
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D004352:Drug Resistance, Microbial; D005461:Fluorine / Q000737:chemistry; D000069349:Linezolid; D008826:Microbial Sensitivity Tests / Q000379:methods; D008956:Models, Chemical; D008968:Molecular Conformation; D010080:Oxazoles / Q000737:chemistry; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010080:Oxazoles; D023303:Oxazolidinones; D005461:Fluorine; D000069349:Linezolid