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PreprintCC BYbioRxiv

Discovery and Optimization of Imidazothiazole Carboxamides as Novel Anti-Tuberculosis Agents

  • L. Meng
  • D. Grant
  • H. Xie
  • R. Ford
  • J. Webb
  • C. W. McNamara
  • P. Sukheja
  • B. Yang1
  • A. K. Chatterjee
  1. 1Calibr-Skaggs Institute for Innovative Medicines, a division of Scripps Research
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Abstract

Screening of the open-access CRESTdb small-molecule library identified the imidazothiazole carboxamide sCQG200 (1) as an initial hit, with activity against H37Rv and Erdman Mycobacterium tuberculosis strains in cholesterol-containing medium (MIC90= 6.88 uM and 4.48 uM, respectively) and against intracellular Mtb (EC50= 3.80 uM). sCQG200 retained activity against drug-resistant Mtb strains, including clinical MDR/XDR isolates. SAR optimization led to analogs 21 and 24 with substantially improved antimycobacterial potency. Mouse pharmacokinetic studies following oral and intravenous administration showed 62.1% and 29.5% oral bioavailability for 21 and 24, respectively. This structurally differentiated chemotype provides a promising starting point for further optimization as antitubercular agent.

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Cite

BibTeXRIS
BibTeX
@misc{meng2026discovery,
  title = {{Discovery and Optimization of Imidazothiazole Carboxamides as Novel Anti-Tuberculosis Agents}},
  author = {L. Meng and D. Grant and H. Xie and R. Ford and J. Webb and C. W. McNamara and P. Sukheja and B. Yang and A. K. Chatterjee},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.21.753226},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.21.753226v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Discovery and Optimization of Imidazothiazole Carboxamides as Novel Anti-Tuberculosis Agents
AU  - L. Meng
AU  - D. Grant
AU  - H. Xie
AU  - R. Ford
AU  - J. Webb
AU  - C. W. McNamara
AU  - P. Sukheja
AU  - B. Yang
AU  - A. K. Chatterjee
PY  - 2026
DA  - 2026/09/21
PB  - bioRxiv
DO  - 10.64898/2026.09.21.753226
UR  - https://www.biorxiv.org/content/10.64898/2026.09.21.753226v1
AB  - Screening of the open-access CRESTdb small-molecule library identified the imidazothiazole carboxamide sCQG200 (1) as an initial hit, with activity against H37Rv and Erdman Mycobacterium tuberculosis strains in cholesterol-containing medium (MIC90= 6.88 uM and 4.48 uM, respectively) and against intracellular Mtb (EC50= 3.80 uM). sCQG200 retained activity against drug-resistant Mtb strains, including clinical MDR/XDR isolates. SAR optimization led to analogs 21 and 24 with substantially improved antimycobacterial potency. Mouse pharmacokinetic studies following oral and intravenous administration showed 62.1% and 29.5% oral bioavailability for 21 and 24, respectively. This structurally differentiated chemotype provides a promising starting point for further optimization as antitubercular agent.
ER  -