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

被引：56

作者：

Shimizu, Kazuki ^{[1
]}

Maruyama, Minako ^{[1
]}

Yasui, Yuka ^{[1
]}

Minegishi, Hidemitsu ^{[1
]}

Ban, Hyun Seung ^{[1
]}

Nakamura, Hiroyuki ^{[1
]}

机构：

[1] Gakushuin Univ, Dept Chem, Fac Sci, Tokyo 1718588, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 04期

关键词：

Hypoxia inducible factor (HIF)-1 alpha; Inhibitor; Carborane; Boronic acid; Angiogenesis; HeLa cells; FACTOR; 1-ALPHA; BIOLOGICAL EVALUATION; ANGIOGENESIS; EXPRESSION; PROTEASOME; PROGNOSIS; CARBORANE; CANCER; TUMORS; FACTOR-1-ALPHA;

D O I：

10.1016/j.bmcl.2009.12.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of boron-containing phenoxyacetanilide derivatives 8a-f, 9a-f, 15, and 16 were synthesized as hypoxia-inducible factor (HIF)-1 alpha inhibitors. Among the compounds synthesized, carboranylphenoxy-acetanilide 16 (GN26361) was found to be a potent inhibitor against HIF-1 alpha accumulation under hypoxic conditions and inhibited the hypoxia-induced HIF-1 transcriptional activity in HeLa cells (IC50 = 0.74 mu M). Compound 16 suppressed hypoxia-induced HIF-1 alpha accumulation and vascular endothelial growth factor mRNA expression in a concentration-dependent manner without affecting the expression of HIF-1 alpha mRNA. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1453 / 1456

页数：4

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