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Synthesis and In Vitro Antibacterial Activity of Novel 3‐Azabicyclo[3.3.0]octanyl Oxazolidinones
Author(s) -
Bhattarai Deepak,
Lee Sun H.,
Seo Seon H.,
Nam Ghilsoo,
Kang Soon B.,
Pae Ae N.,
Kim Eunice E.,
Oh Taegwon,
Cho SangNae,
Keum Gyochang
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01404.x
Subject(s) - linezolid , morpholine , in vitro , chemistry , acetamide , herg , antibacterial activity , mycobacterium tuberculosis , stereochemistry , bacteria , combinatorial chemistry , biochemistry , biology , tuberculosis , organic chemistry , vancomycin , medicine , potassium channel , biophysics , pathology , genetics , staphylococcus aureus
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.