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

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5239-43. doi: 10.1016/j.bmcl.2011.07.043. Epub 2011 Jul 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Quinazolinones