Pyrimidine derivatives with antitubercular activity

  • Eur J Med Chem. 2023 Jan 15:246:114946. doi: 10.1016/j.ejmech.2022.114946.
Vladimir Finger  1 ,  Martin Kufa  1 ,  Ondrej Soukup  2 ,  Daniele Castagnolo  3 ,  Jaroslav Roh  4 ,  Jan Korabecny  5
Affiliations
  • 1. Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 50005 Hradec Kralove, Czech Republic; Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec, Kralove, Czech Republic.
  • 2. Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec, Kralove, Czech Republic.
  • 3. Department of Chemistry, University College London, 20 Gordon Street, WC1H 0AJ, London, United Kingdom.
  • 4. Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 50005 Hradec Kralove, Czech Republic. Electronic address: [email protected].
  • 5. Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec, Kralove, Czech Republic. Electronic address: [email protected].
PMID: 36459759 DOI: 10.1016/j.ejmech.2022.114946
Abstract

Small molecules with antitubercular activity containing the pyrimidine motif in their structure have gained more attention after three drugs, namely GSK 2556286 (GSK-286), TBA-7371 and SPR720, have entered clinical trials. This review provides an overview of recent advances in the hit-to-lead drug discovery studies of antitubercular pyrimidine-containing compounds with the aim to highlight their structural diversity. In the first part, the review discusses the pyrimidine compounds according to their targets, pinpointing the structure-activity relationships of each pyrimidine family. The second part of this review is concentrated on antitubercular pyrimidine derivatives with a yet unexplored or speculative target, dividing the compounds according to their structural types.

Keywords
Drug development; Mycobacterium tuberculosis; Pyrimidine; Structure-activity relationships; Tuberculosis.
Products