Synthesis and biological evaluation of 5-arylamino-6-chloro-1H-indazole-4,7-diones as inhibitors of protein kinase B/Akt

被引：30

作者：

Ko, Jong Hee

Yeon, Seung Woo

Ryu, Jung Su

Kim, Tae-Yong

Song, Eun-Ha

You, Hea-Jung

Park, Rae-Eun

Ryu, Chung-Kyu ^{[1
]}

机构：

[1] Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea

[2] ILDONG Pharmaceut Co Ltd, ILDONG Res Labs, Kyonggi Do 449910, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 23期

关键词：

akt; inhibitor; 1H-indazole-4,7-dione; antitumor;

D O I：

10.1016/j.bmcl.2006.08.120

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 5-arylamino-6-chloro-1H-indazole-4,7-diones were synthesized and evaluated for their inhibitory activity on protein kinase B/Akt. The compounds exhibited a potent Akt1 inhibitory activity. Further mechanistic study revealed that they might have dual inhibitory effects on both activity and phosphorylation of Akt1 in PC-3 tumor cell line. (c) 2006 Elsevier Ltd. All rights reserved.

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收藏

页码：6001 / 6005

页数：5

相关论文

共 11 条

[1] Glycogen synthase kinase-3: Properties, functions, and regulation [J].

Ali, A ;

Hoeflich, KP ;

Woodgett, JR .

CHEMICAL REVIEWS, 2001, 101 (08) :2527-2540

[2] The Akt/PKB pathway: molecular target for cancer drug discovery [J].

Cheng, JQ ;

Lindsley, CW ;

Cheng, GZ ;

Yang, H ;

Nicosia, SV .

ONCOGENE, 2005, 24 (50) :7482-7492

[3] The phosphoinositide 3-kinase/Akt1/Par-4 axis: A cancer-selective therapeutic target [J].

Goswami, A ;

Ranganathan, P ;

Rangnekar, VM .

CANCER RESEARCH, 2006, 66 (06) :2889-2892

[4]

KO JH, 2004, YAKHAK HOEJI, V48, P105

[5]

McMenamin ME, 1999, CANCER RES, V59, P4291

[6] Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines [J].

Nakatani, K ;

Thompson, DA ;

Barthel, A ;

Sakaue, H ;

Liu, W ;

Weigel, RJ ;

Roth, RA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (31) :21528-21532

[7] The protein kinase B/Akt signalling pathway in human malignancy [J].

Nicholson, KM ;

Anderson, NG .

CELLULAR SIGNALLING, 2002, 14 (05) :381-395

[8] Unravelling the activation mechanisms of protein kinase B/Akt [J].

Scheid, MP ;

Woodgett, JR .

FEBS LETTERS, 2003, 546 (01) :108-112

[9] NEW COLORIMETRIC CYTOTOXICITY ASSAY FOR ANTICANCER-DRUG SCREENING [J].

SKEHAN, P ;

STORENG, R ;

SCUDIERO, D ;

MONKS, A ;

MCMAHON, J ;

VISTICA, D ;

WARREN, JT ;

BOKESCH, H ;

KENNEY, S ;

BOYD, MR .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1990, 82 (13) :1107-1112

[10] MOLECULAR-CLONING OF THE AKT ONCOGENE AND ITS HUMAN HOMOLOGS AKT1 AND AKT2 - AMPLIFICATION OF AKT1 IN A PRIMARY HUMAN GASTRIC ADENOCARCINOMA [J].

STAAL, SP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (14) :5034-5037