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Pyrimidine derivatives with antitubercular activity.

Vladimir Finger1, Martin Kufa1, Ondrej Soukup2

  • 1Faculty 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.

European Journal of Medicinal Chemistry
|December 2, 2022
PubMed
Summary

Pyrimidine compounds show promise for treating tuberculosis (TB). This review highlights structural diversity and target-based structure-activity relationships for these antitubercular small molecules, aiding drug discovery.

Keywords:
Drug developmentMycobacterium tuberculosisPyrimidineStructure-activity relationshipsTuberculosis

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Area of Science:

  • Medicinal Chemistry
  • Drug Discovery
  • Tuberculosis Research

Background:

  • Small molecules featuring the pyrimidine motif are gaining traction for antitubercular applications.
  • Three pyrimidine-based compounds (GSK 2556286, TBA-7371, SPR720) have advanced into clinical trials for tuberculosis treatment.

Purpose of the Study:

  • To review recent advancements in hit-to-lead drug discovery for antitubercular pyrimidine-containing compounds.
  • To emphasize the structural diversity of these promising therapeutic agents.
  • To correlate structural features with biological activity against Mycobacterium tuberculosis.

Main Methods:

  • Literature review of recent studies on pyrimidine derivatives with antitubercular activity.
  • Classification of compounds based on their molecular targets.
  • Analysis of structure-activity relationships (SAR) within different pyrimidine chemical families.
  • Categorization of compounds with unexplored or speculative targets by structural type.

Main Results:

  • Detailed overview of pyrimidine compounds targeting known pathways in tuberculosis.
  • Exploration of novel pyrimidine derivatives with potential activity against unexplored or speculative targets.
  • Identification of key structural features contributing to antitubercular efficacy.
  • Highlighting of structural diversity across various pyrimidine-based scaffolds.

Conclusions:

  • Pyrimidine-containing small molecules represent a significant and diverse class of compounds for tuberculosis drug discovery.
  • Understanding structure-activity relationships is crucial for optimizing antitubercular pyrimidine derivatives.
  • Further research into compounds with novel targets holds potential for developing next-generation TB therapies.