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

被引：39

作者：

Maeda, Y

Nakano, M

Sato, H

Miyazaki, Y

Schweiker, SL

Smith, JL

Truesdale, AT

机构：

[1] GlaxoSmithKline KK, Tsukuba Res Labs, Dept Chem, Tsukuba, Ibaraki 3004247, Japan

[2] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 15期

关键词：

glycogen synthase kinase-3 inhibitors;

D O I：

10.1016/j.bmcl.2004.05.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Modeling studies of a furo[2,3-d]pyrimidine GSK-3 hit compound 1 superimposed onto the X-ray crystal structure of a legacy pyrazolo[3,4-c]pyridazine GSK-3 inhibitor 2 led to the identification of 4-acylamino-6-arylfuro[2,3-d]pyrimidine template 3. Synthesis of analogues based on template 3 has resulted in a number of potent and selective GSK-3beta inhibitors. The most potent and selective compound was the m-pyridyl analogue 24. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：3907 / 3911

页数：5

共 19 条

[1]

ADAMS JJ, 2003, Patent No. 022852

[2] Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription [J].

Coghlan, MP ;

Culbert, AA ;

Cross, DAE ;

Corcoran, SL ;

Yates, JW ;

Pearce, NJ ;

Rausch, OL ;

Murphy, GJ ;

Carter, PS ;

Cox, LR ;

Mills, D ;

Brown, MJ ;

Haigh, D ;

Ward, RW ;

Smith, DG ;

Murray, KJ ;

Reith, AD ;

Holder, JC .

CHEMISTRY & BIOLOGY, 2000, 7 (10) :793-803

[3] SEPARATION AND CHARACTERIZATION OF GLYCOGEN-SYNTHASE KINASE-3, GLYCOGEN-SYNTHASE KINASE-4 AND GLYCOGEN-SYNTHASE KINASE-5 FROM RABBIT SKELETAL-MUSCLE [J].

COHEN, P ;

YELLOWLEES, D ;

AITKEN, A ;

DONELLADEANA, A ;

HEMMINGS, BA ;

PARKER, PJ .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1982, 124 (01) :21-35

[4] The renaissance of GSK3 [J].

Cohen, P ;

Frame, S .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2001, 2 (10) :769-776

[5] 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

[6] Synthesis and discovery of macrocyclic polyoxygenated bis-7-azaindolylmaleimides as a novel series of potent and highly selective glycogen synthase kinase-3β inhibitors [J].

Kuo, GH ;

Prouty, C ;

DeAngelis, A ;

Shen, L ;

O'Neill, DJ ;

Shah, C ;

Connolly, PJ ;

Murray, WV ;

Conway, BR ;

Cheung, P ;

Westover, L ;

Xu, JZ ;

Look, RA ;

Demarest, KT ;

Emanuel, S ;

Middleton, SA ;

Jolliffe, L ;

Beavers, MP ;

Chen, X .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (19) :4021-4031

[7] Indirubins inhibit glycogen synthase kinase-3β and CDK5/P25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease -: A property common to most cycline-dependent kinase inhibitors? [J].

Leclerc, S ;

Garnier, M ;

Hoessel, R ;

Marko, D ;

Bibb, JA ;

Snyder, GL ;

Greengard, P ;

Biernat, J ;

Wu, YZ ;

Mandelkow, EM ;

Eisenbrand, G ;

Meijer, L .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (01) :251-260

[8] Paullones are potent inhibitors of glycogen synthase kinase-3β and cyclin-dependent kinase 5/p25 [J].

Leost, M ;

Schultz, C ;

Link, A ;

Wu, YZ ;

Biernat, J ;

Mandelkow, EM ;

Bibb, JA ;

Snyder, GL ;

Greengard, P ;

Zaharevitz, DW ;

Gussio, R ;

Senderowicz, AM ;

Sausville, EA ;

Kunick, C ;

Meijer, L .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 2000, 267 (19) :5983-5994

[9] ALZHEIMER'S DISEASE-LIKE PHOSPHORYLATION OF THE MICROTUBULE-ASSOCIATED PROTEIN TAU BY GLYCOGEN SYNTHASE KINASE-3 IN TRANSFECTED MAMMALIAN CELLS [J].

LOVESTONE, S ;

REYNOLDS, CH ;

LATIMER, D ;

DAVIS, DR ;

ANDERTON, BH ;

GALLO, JM ;

HANGER, D ;

MULOT, S ;

MARQUARDT, B ;

STABEL, S ;

WOODGETT, JR ;

MILLER, CCJ .

CURRENT BIOLOGY, 1994, 4 (12) :1077-1086

[10] First non-ATP competitive glycogen synthase kinase 3 β (GSK-3β) inhibitors:: Thiadiazolidinones (TDZD) as potential drugs for the treatment of Alzheimer's disease [J].

Martinez, A ;

Alonso, M ;

Castro, A ;

Pérez, C ;

Moreno, FJ .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (06) :1292-1299

← 1 2 →