Design, Synthesis, and Biological Evaluation of Pyrazolo[1,5-a]pyridine-3-carboxamides as Novel Antitubercular Agents

  • ACS Med Chem Lett. 2015 Jun 11;6(7):814-8. doi: 10.1021/acsmedchemlett.5b00176.
Jian Tang  1 ,  Bangxing Wang  2 ,  Tian Wu  3 ,  Junting Wan  3 ,  Zhengchao Tu  3 ,  Moses Njire  1 ,  Baojie Wan  4 ,  Scott G Franzblauc  4 ,  Tianyu Zhang  3 ,  Xiaoyun Lu  3 ,  Ke Ding  3
Affiliations
  • 1. State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science , #190 Kai Yuan Avenue, Guangzhou 510530, China ; University of Chinese Academy of Sciences , #19 Yuquan Road, Beijing 100049, China.
  • 2. State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science , #190 Kai Yuan Avenue, Guangzhou 510530, China ; College of Life Science, Anhui University , 111 Jiulong Road, Hefei 230601, China.
  • 3. State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science , #190 Kai Yuan Avenue, Guangzhou 510530, China.
  • 4. Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago , 833 South Wood Street, Chicago, Illinois 60612, United States.
PMID: 26191372 DOI: 10.1021/acsmedchemlett.5b00176
Abstract

A series of pyrazolo[1,5-a]pyridine-3-carboxamide derivatives were designed and synthesized as new anti-Mycobacterium tuberculosis (Mtb) agents. The compounds exhibit promising in vitro potency with nanomolar MIC values against the drug susceptive H37Rv strain and a panel of clinically isolated multidrug-resistant Mtb (MDR-TB) strains. One of the representative compounds (5k) significantly reduces the Bacterial burden in an autoluminescent H37Ra infected mouse model, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.

Keywords
Antitubercular agent; H37Rv; pyrazolo[1,5-a]pyridine; structure−activity relationship; tuberculosis.