Rational design of 4-amino-5,6-diaryl-furo[2,3-d]pyrimidines as potent glycogen synthase kinase-3 inhibitors

被引：41

作者：

Miyazaki, Yasushi ^{[1
,3
]}

Maeda, Yutaka ^{[1
,3
]}

Sato, Hideyuki ^{[1
,3
]}

Nakano, Masato ^{[1
,3
]}

Mellor, Geoffrey W. ^{[2
]}

机构：

[1] GlaxoSmithKline Inc, Dev Affairs Dev, Shibuya Ku, Tokyo 1518586, Japan

[2] GlaxoSmithKline Inc, Mol Discovery Res Screening & Compound Profiling, New Frontiers Sci Pk, Harlow CM19 5AW, Essex, England

[3] GlaxoSmithKline Inc, Tsukuba Res Labs, Dept Chem, Tsukuba, Ibaraki 3004247, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 06期

关键词：

glycogen synthase kinase-3;

D O I：

10.1016/j.bmcl.2008.01.113

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

4-Amino-5,6-diaryl-furo[2,3-d] pyrimidines have been identified as inhibitors of glycogen synthase kinase-3b (GSK-3 beta). One representative derivative, 4-amino-5-(4-(benzenesulfonylamino)-phenyl)-6-(3-pyridyl)-furo[2,3-d] pyrimidine (12) exhibited potent GSK-3b inhibitory activity in low nanomolar level of IC50. The binding mode was proposed from a docking study. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1967 / 1971

页数：5

共 15 条

[1] Oncogenic kinase signalling [J].

Blume-Jensen, P ;

Hunter, T .

NATURE, 2001, 411 (6835) :355-365

[2]

Bullock William H., 2002, Current Topics in Medicinal Chemistry, V2, P915, DOI 10.2174/1568026023393255

[3] Protein kinases - the major drug targets of the twenty-first century? [J].

Cohen, P .

NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (04) :309-315

[4] Specificity and mechanism of action of some commonly used protein kinase inhibitors [J].

Davies, SP ;

Reddy, H ;

Caivano, M ;

Cohen, P .

BIOCHEMICAL JOURNAL, 2000, 351 (351) :95-105

[5] Inhibitors of glycogen synthase kinase-3: future therapy for unmet medical needs? [J].

Dorronsoro, I ;

Castro, A ;

Martinez, A .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2002, 12 (10) :1527-1536

[6] Glycogen synthase kinase 3: an emerging therapeutic target [J].

Eldar-Finkelman, H .

TRENDS IN MOLECULAR MEDICINE, 2002, 8 (03) :126-132

[7] PROTEIN-KINASES AND PHOSPHATASES - THE YIN AND YANG OF PROTEIN-PHOSPHORYLATION AND SIGNALING [J].

HUNTER, T .

CELL, 1995, 80 (02) :225-236

[8] Structural basis for control by phosphorylation [J].

Johnson, LN ;

Lewis, RJ .

CHEMICAL REVIEWS, 2001, 101 (08) :2209-2242

[9]

Kaidanovich Oksana, 2002, Expert Opin Ther Targets, V6, P555

[10] 4-Acylamino-6-arylfuro[2,3-d]pyrimidines:: potent and selective glycogen synthase kinase-3 inhibitors [J].

Maeda, Y ;

Nakano, M ;

Sato, H ;

Miyazaki, Y ;

Schweiker, SL ;

Smith, JL ;

Truesdale, AT .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (15) :3907-3911

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