The discovery of tetrahydro-β-carbolines as inhibitors of the kinesin Eg5

被引：95

作者：

Barsanti, Paul A. ^{[1
]}

Wang, Weibo ^{[1
]}

Ni, Zhi-Jie ^{[1
]}

Duhl, David ^{[1
]}

Brammeier, Nathan ^{[1
]}

Martin, Eric ^{[1
]}

Bussiere, Dirksen ^{[1
]}

Walter, Annette O. ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, Emeryville, CA 94608 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 01期

关键词：

Eg5; KSP; Kinesin; SPINDLE PROTEIN KSP; POTENT;

D O I：

10.1016/j.bmcl.2009.11.012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of tetrahydro-beta-carbolines were identified by HTS as inhibitors of the kinesin Eg5. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus of removing potential metabolic liabilities and improving cellular potency. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：157 / 160

页数：4

共 11 条

[1]

CHU QS, 2004, 40 ASCO ANN M NEW OR, V22

[2] Kinesin spindle protein (KSP) inhibitors. Part 4: Structure-based design of 5-alkylamino-3,5-diaryl-4,5-dihydropyrazoles as potent, water-soluble inhibitors of the mitotic kinesin KSP [J].

Cox, CD ;

Torrent, M ;

Breslin, MJ ;

Mariano, BJ ;

Whitman, DB ;

Coleman, PJ ;

Buser, CA ;

Walsh, ES ;

Hamilton, K ;

Schaber, MD ;

Lobell, RB ;

Tao, WK ;

South, VJ ;

Kohl, NE ;

Yan, YW ;

Kuo, LC ;

Prueksaritanont, T ;

Slaughter, DE ;

Li, CZ ;

Mahan, E ;

Lu, B ;

Hartman, GD .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (12) :3175-3179

[3] Kinesin spindle protein (KSP) inhibitors. Part 1: The discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of the mitotic kinesin KSP [J].

Cox, CD ;

Breslin, MJ ;

Brenda, JM ;

Coleman, PJ ;

Buser, CA ;

Walsh, ES ;

Hamilton, K ;

Huber, HE ;

Kohl, NE ;

Torrent, M ;

Yan, YW ;

Kuo, LC ;

Hartman, GD .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (08) :2041-2045

[4] Kinesin motors as molecular machines [J].

Endow, SA .

BIOESSAYS, 2003, 25 (12) :1212-1219

[5] Inhibitors of human mitotic kinesin Eg5: Characterization of the 4-phenyl-tetrahydrolsoquinoline lead series [J].

Tarby, CM ;

Kaltenbach, RF ;

Huynh, T ;

Pudzianowski, A ;

Shen, H ;

Ortega-Nanos, M ;

Sheriff, S ;

Newitt, JA ;

McDonnell, PA ;

Burford, N ;

Fairchild, CR ;

Vaccaro, W ;

Chen, Z ;

Borzilleri, RM ;

Naglich, J ;

Lombardo, LJ ;

Gottardis, M ;

Trainor, GL ;

Roussell, DL .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (08) :2095-2100

[6]

WANG W, 2004, Patent No. 04113335

[7]

WANG W, 2004, Patent No. 04111058

[8]

WANG W, 2005, Patent No. 05070930

[9]

WANG W, 2005, Patent No. 05228002

[10] Inhibition of a mitotic motor protein: Where, how, and conformational consequences [J].

Yan, YW ;

Sardana, V ;

Xu, B ;

Homnick, C ;

Halczenko, W ;

Buser, CA ;

Schaber, M ;

Hartman, GD ;

Huber, HE ;

Kuo, LC .

JOURNAL OF MOLECULAR BIOLOGY, 2004, 335 (02) :547-554

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