Synthesis and structure-activity relationship of imidazo(1,2-a)thieno(3,2-e)pyrazines as IKK-β inhibitors

被引：34

作者：

Belema, Makonen ^{[1
]}

Bunker, Amy

Nguyen, Van N.

Beaulieu, Francis

Ouellet, Carl

Qu, Yuping

Zhang, Yunhui

Martel, Alain

Burke, James R.

Mclntyre, Kim W.

Pattoli, Mark A.

Daloisio, Connie

Gillooly, Kathleen M.

Clarke, Wendy J.

Brassil, Patrick J.

Zusi, F. Chris

Vyasa, Dolatrai M.

机构：

[1] Bristol Myers Squibb Pharmaceut Res Inst, Wallingford, CT 06492 USA

[2] Bristol Myers Squibb Pharmaceut Res Inst, Quebec City, PQ J5R 1J1, Canada

[3] Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 15期

关键词：

IKK; NF-KB; TNF-alpha; imidazothienopyrazine;

D O I：

10.1016/j.bmcl.2007.05.031

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The identification of a potent series of IKK-beta selective inhibitors based on an imidazothienopyrazine template and the oral efficacy of one such analog (22j) in the LPS-induced TNF-alpha release mouse model are described. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：4284 / 4289

页数：6

共 25 条

[1]

ADAMS JL, 2004, PROTEIN CRYSTALLOGRA, pCH2

[2]

Ames D. E., 1980, J CHEM SOC P, P1384

[3]

AMES DE, 1985, J CHEM RES MINIPRINT, V5, P1683

[4] NF-κB regulation by IκB kinase-2 in rheumatoid arthritis synoviocytes [J].

Aupperle, KR ;

Bennett, BL ;

Han, ZN ;

Boyle, DL ;

Manning, AM ;

Firestein, GS .

JOURNAL OF IMMUNOLOGY, 2001, 166 (04) :2705-2711

[5] Synthesis and biological evaluation of 4-amino derivatives of benzimidazoquinoxaline, benzimidazoquinoline, and benzopyrazoloquinazoline as potent IKK inhibitors [J].

Beaulieu, Francis ;

Ouellet, Carl ;

Ruediger, Edward H. ;

Belema, Makonen ;

Qiu, Yuping ;

Yang, Xuejie ;

Banville, Jacques ;

Burke, James R. ;

Gregor, Kurt R. ;

MacMaster, John F. ;

Martel, Alain ;

McIntyre, Kim W. ;

Pattoli, Mark A. ;

Zusi, F. Christopher ;

Vyas, Dolatrai .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (05) :1233-1237

[6]

BELEMA M, Patent No. 6933294

[7] Inhibition of IKK-2 by 2-[(aminocarbonyl)amino]-5-acetylenyl-3-thiophenecarboxamides [J].

Bonafoux, D ;

Bonar, S ;

Christine, L ;

Clare, M ;

Donnelly, A ;

Guzova, J ;

Kishore, N ;

Lennon, P ;

Libby, A ;

Mathialagan, S ;

McGhee, W ;

Rouw, S ;

Sommers, C ;

Tollefson, M ;

Tripp, C ;

Weier, R ;

Wolfson, S ;

Min, Y .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (11) :2870-2875

[8] HETEROCYCLES .167. TELE-SUBSTITUTION AND OTHER TRANSFORMATIONS OF IMIDAZO[1,2-A]-AND S-TRIAZOLO[4,3-A]PYRAZINES [J].

BRADAC, J ;

FUREK, Z ;

JANEZIC, D ;

MOLAN, S ;

SMERKOLJ, I ;

STANOVNIK, B ;

TISLER, M ;

VERCEK, B .

JOURNAL OF ORGANIC CHEMISTRY, 1977, 42 (26) :4197-4201

[9] Peptides corresponding to the N and C termini of IκB-α, -β, and -ε as probes of the two catalytic subunits of IκB kinase, IKK-1 and IKK-2 [J].

Burke, JR ;

Wood, MK ;

Ryseck, RP ;

Walther, S ;

Meyers, CA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (51) :36146-36152

[10] BMS-345541 is a highly selective inhibitor of IκB kinase that binds at an allosteric site of the enzyme and blocks NF-κB-dependent transcription in mice [J].

Burke, JR ;

Pattoli, MA ;

Gregor, KR ;

Brassil, PJ ;

MacMaster, JF ;

McIntyre, KW ;

Yang, XX ;

Iotzova, VS ;

Clarke, W ;

Strnad, J ;

Qiu, YP ;

Zusi, FC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1450-1456

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