Synthesis and evaluation of quinazolin-4-ones as hypoxia-inducible factor-1α inhibitors.

Medicinal Chemistry


Quinazolin-4-one 1 was identified as an inhibitor of the HIF-1α transcriptional factor from a high-throughput screen. HIF-1α up-regulation is common in many cancer cells. In this Letter, we describe an efficient one-pot sequential reaction for the synthesis of quinazolin-4-one 1 analogues. The structure-activity relationship (SAR) study led to the 5-fold more potent analogue, 16.


Huang, Wenwei; Huang, Ruili; Attene-Ramos, Matias S; Sakamuru, Srilatha; Englund, Erika E; Inglese, James; Austin, Christopher; Xia, Menghang;


  • Chemistry Techniques, Synthetic
  • High-Throughput Screening Assays
  • Hypoxia-Inducible Factor 1, alpha Subunit/ antagonists & inhibitors
  • Hypoxia-Inducible Factor 1, alpha Subunit/ metabolism
  • Molecular Structure
  • Quinazolinones/ chemical synthesis
  • Quinazolinones/ chemistry
  • Quinazolinones/ pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

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