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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Huang, Wenwei¹  Huang, Ruili¹  Attene-Ramos, Matias S.¹  Sakamuru, Srilatha¹  Englund, Erika E.¹  Inglese, James¹  Austin, Christopher P.¹  Xia, Menghang¹ 

[1] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA

关键词: Hypoxia-inducible factor-1 alpha;    Quinazolin-4-ones;    Parallel synthesis;   

DOI  :  10.1016/j.bmcl.2011.07.043

来源: Elsevier

【 摘 要 】

Quinazolin-4-one 1 was identified as an inhibitor of the HIF-1 alpha transcriptional factor from a high-throughput screen. HIF-1 alpha 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. Published by Elsevier Ltd.

【 授权许可】

Free