Boron-containing phenoxyacetanilide derivatives as hypoxia-inducible factor (HIF)-1alpha inhibitors.

Abstract

A series of boron-containing phenoxyacetanilide derivatives 8a-f, 9a-f, 15, and 16 were synthesized as hypoxia-inducible factor (HIF)-1alpha inhibitors. Among the compounds synthesized, carboranylphenoxyacetanilide 16 (GN26361) was found to be a potent inhibitor against HIF-1alpha accumulation under hypoxic conditions and inhibited the hypoxia-induced HIF-1 transcriptional activity in HeLa cells (IC50=0.74 microM). Compound 16 suppressed hypoxia-induced HIF-1alpha accumulation and vascular endothelial growth factor mRNA expression in a concentration-dependent manner without affecting the expression of HIF-1alpha mRNA.

• Authors: Kazuki Shimizu, Minako Maruyama, Yuka Yasui, Hidemitsu Minegishi, Hyun Seung Ban, Hiroyuki Nakamura
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 4 Pg. 1453-6 (Feb 15 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20083404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Acetanilides
• Boron Compounds
• Boronic Acids
• GN 26361
• Hypoxia-Inducible Factor 1, alpha Subunit
• Phenols
• RNA, Messenger
• Boron

Topics

• Acetanilides (chemical synthesis, chemistry, pharmacology)
• Boron (chemistry)
• Boron Compounds (chemical synthesis, chemistry, pharmacology)
• Boronic Acids
• Gene Expression Regulation (drug effects)
• HeLa Cells
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, genetics)
• Inhibitory Concentration 50
• Phenols (chemistry)
• RNA, Messenger (biosynthesis, genetics)
• Transcription, Genetic