Recent contributions of pyridazine as a privileged scaffold of anticancer agents in medicinal chemistry: An updated review

Bioorg Med Chem. 2024 Sep 1:111:117847. doi: 10.1016/j.bmc.2024.117847. Epub 2024 Jul 28.

Abstract

Pyridazine, as a privileged scaffold, has been extensively utilized in drug development due to its multiple biological activities. Especially around its distinctive anticancer property, a massive number of pyridazine-containing compounds have been synthesized and evaluated that target a diverse array of biological processes involved in cancer onset and progression. These include glutaminase 1 (GLS1) inhibitors, tropomyosin receptor kinase (TRK) inhibitors, and bromodomain containing protein (BRD) inhibitors, targeting aberrant tumor metabolism, cell signal transduction and epigenetic modifications, respectively. Pyridazine moieties functioned as either core frameworks or warheads in the above agents, exhibiting promising potential in cancer treatment. Therefore, the review aims to summarize the recent contributions of pyridazine derivatives as potent anticancer agents between 2020 and 2024, focusing mainly on their structure-activity relationships (SARs) and development strategies, with a view to show that the application of the pyridazine scaffold by different medicinal chemists provides new insights into the rational design of anticancer drugs.

Keywords: Anticancer; Drug design; Pyridazine; Structure-activity relationships.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Proliferation / drug effects
  • Chemistry, Pharmaceutical
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Neoplasms / drug therapy
  • Pyridazines* / chemical synthesis
  • Pyridazines* / chemistry
  • Pyridazines* / pharmacology
  • Structure-Activity Relationship

Substances

  • Pyridazines
  • Antineoplastic Agents
  • pyridazine