Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase

Jialin Mao, Hyungjin Eoh, Rong He, Yuehong Wang, Baojie Wan, Scott G. Franzblau, Dean C. Crick, Alan P. Kozikowski

Research output: Contribution to journalArticlepeer-review

Abstract

We report on a target-based approach to identify possible Mycobacterium tuberculosis DXS inhibitors from the structure of a known transketolase inhibitor. A small focused library of analogs was assembled in order to begin elucidating some meaningful structure-activity relationships of 3-(4-chloro-phenyl)-5-benzyl-4H-pyrazolo[1,5-a]pyrimidin-7-one. Ultimately we found that 2-methyl-3- (4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one, although still weak, was able to inhibit M. tuberculosis DXS with an IC50 of 10.6 μM.

Original languageEnglish (US)
Pages (from-to)5320-5323
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number19
DOIs
StatePublished - Oct 1 2008

Keywords

  • DXS
  • Drug design
  • Enzyme
  • SAR
  • Tuberculosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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