title: Synthesis and in vitro antibacterial activity of novel 3-azabicyclo[3.3.0]octanyl oxazolidinones.
abstract: We synthesized a series of oxazolidinone-type antibacterials in which morpholine C-ring of linezolid has been modified by substituted 3-azabicyclo[3.3.0]octanyl rings. Acetamide or 1,2,3-triazole heterocycle was used as C-5 side chain of oxazolidinone. The resulting series of compounds was then screened in vitro against panel of susceptible and resistant Gram-positive, Gram-negative bacteria, and Mycobacterium tuberculosis (Mtb). Several analogs in this series exhibited potent in vitro antibacterial activity comparable or superior to linezolid against the tested bacteria. Compounds 10a, 10b, 11a, and 15a displayed highly potent activity against M. tuberculosis. Selected compound 10b showed good human microsomal stability and CYP-profile, and showed low activity against hERG channel.
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhattarai
authors.forename: Sun H
authors.initials: SH
authors.lastname: Lee
authors.forename: Seon H
authors.initials: SH
authors.lastname: Seo
authors.forename: Ghilsoo
authors.initials: G
authors.lastname: Nam
authors.forename: Soon B
authors.initials: SB
authors.lastname: Kang
authors.forename: Ae N
authors.initials: AN
authors.lastname: Pae
authors.forename: Eunice E
authors.initials: EE
authors.lastname: Kim
authors.forename: Taegwon
authors.initials: T
authors.lastname: Oh
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
authors.forename: Gyochang
authors.initials: G
authors.lastname: Keum
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015195:Drug Design; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D008862:Microsomes, Liver / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D051638:Ether-A-Go-Go Potassium Channels; D023303:Oxazolidinones; D014230:Triazoles; C030686:acetamide; D003577:Cytochrome P-450 Enzyme System