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Pyrido[1,2‐ a ]benzimidazole‐Based Agents Active Against Tuberculosis (TB), Multidrug‐Resistant (MDR) TB and Extensively Drug‐Resistant (XDR) TB
Author(s) -
Pieroni Marco,
Tipparaju Suresh K.,
Lun Shichun,
Song Yang,
Sturm A. Willem,
Bishai William R.,
Kozikowski Alan P.
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000490
Subject(s) - tuberculosis , mycobacterium tuberculosis , benzimidazole , multiple drug resistance , virology , drug , human immunodeficiency virus (hiv) , extensively drug resistant tuberculosis , medicine , vero cell , potency , drug resistance , pharmacology , microbiology and biotechnology , biology , chemistry , in vitro , virus , organic chemistry , pathology , biochemistry
The struggle against tuberculosis (TB) is still far from over. TB, caused by Mycobacterium tuberculosis , is one of the deadliest infections worldwide. Co‐infection with human immunodeficiency virus (HIV) and the emergence of multidrug‐resistant tuberculosis (MDR‐TB) and extensively drug‐resistant tuberculosis (XDR‐TB) strains have further increased the burden for this disease. Herein, we report the discovery of 2‐(4‐chlorobenzyl)‐3‐methyl‐1‐oxo‐1 H ,5 H ‐pyrido[1,2‐ a ]benzimidazole‐4‐carbonitrile as an effective antitubercular agent and the structural modifications of this molecule that have led to analogues with improved potency and lower toxicity. A number of these derivatives were also active at sub‐micromolar concentrations against resistant TB strains and devoid of apparent toxicity to Vero cells, thereby underscoring their value as novel scaffolds for the development of new anti‐TB drugs.