Synthesis and structure–activity relationship studies of novel [6, 6, 5] tricyclic oxazolidinone derivatives as potential antibacterial agents. Issue 10 (15th May 2015)

• Record Type: Journal Article
• Authors: Xue, Tao; Ding, Shi; Guo, Bin; Chu, Wenjing; Wang, Hui; Yang, Yushe
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 10(2015)
• Page Start: 2203
• Page End: 2210
• Publication Date: 2015-05-15
• Subjects: [6, 6, 5] tricyclic core structure -- Structure–activity relationship -- Antibacterial activity -- Liver microsomal stability; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.03.053
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: In our previous Letter, we reported the discovery of a novel benzoxazinyl-oxazolidinone antibacterial candidate2 . In order to identify a potential backup compound, extensive modifications on the B/C ring and C3 side chain were undertaken. A series of novel [6, 6, 5] tricyclic analogues were synthesized and their in vitro antibacterial activities were tested against a panel of susceptible and resistant Gram-positive pathogens. Among of them, benzothiazinyl-oxazolidinones with acetamide or thioamide as C3 side chains exhibited moderate to good antibacterial activity, such as compounds54, 58, 59 and63 . In vitro liver microsomal stability was further evaluated and the results manifested that compounds54 and58 were both metabolically stable in rat and human liver microsomes. Additionally, insights gained from this investigation should provide directions for the further research of new oxazolidinone antibiotics.