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

…, MS Attene-Ramos, S Sakamuru, EE Englund…

Index: Huang, Wenwei; Huang, Ruili; Attene-Ramos, Matias S.; Sakamuru, Srilatha; Englund, Erika E.; Inglese, James; Austin, Christopher P.; Xia, Menghang Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 18 p. 5239 - 5243

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Citation Number: 7

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.