Novel Mps1 kinase inhibitors: From purine to pyrrolopyrimidine and quinazoline leads

被引：15

作者：

Bursavich, Matthew G. ^{[1
]}

Dastrup, David ^{[1
]}

Shenderovich, Mark ^{[1
]}

Yager, Kraig M. ^{[1
]}

Cimbora, Daniel M. ^{[2
]}

Williams, Brandi ^{[2
]}

Kumar, D. Vijay ^{[1
]}

机构：

[1] Myrexis Inc, Med Chem, Salt Lake City, UT 84108 USA

[2] Myrexis Inc, Vitro Pharmacol, Salt Lake City, UT 84108 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 24期

关键词：

Mps1; TTK; Protein kinase inhibitors; Scaffold hopping; Conformational restriction; Structure-based design; Cancer; Purines; Pyrrolopyrimidines; Quinazoline; POTENT;

D O I：

10.1016/j.bmcl.2013.10.008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Mps1, also known as TTK, is a mitotic checkpoint protein kinase that has become a promising new target of cancer research. In an effort to improve the lead-likeness of our recent Mps1 purine lead compounds, a scaffold hopping exercise has been undertaken. Structure-based design, principles of conformational restriction, and subsequent scaffold hopping has led to novel pyrrolopyrimidine and quinazoline Mps1 inhibitors. These new single-digit nanomolar leads provide the basis for developing potent, novel Mps1 inhibitors with improved drug-like properties. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：6829 / 6833

页数：5

共 17 条

[1] Ligand efficiency indices as guideposts for drug discovery
Abad-Zapatero, C
Metz, JT
[J]. DRUG DISCOVERY TODAY, 2005, 10 (07) : 464 - 469
[2] [Anonymous], ALL NEWL PREP COMP W
[3] [Anonymous], 2011, IM WER MAD ACC DISC
[4] [Anonymous], 2008, J MED CHEM
[5] Expedient parallel synthesis of 2-amino-4-heteroarylpyrimidines
Bursavich, MG
Lombardi, S
Gilbert, AM
[J]. ORGANIC LETTERS, 2005, 7 (19) : 4113 - 4116
[6] Synthesis and SAR of new pyrazolo[4,3-h]quinazoline-3-carboxamide derivatives as potent and selective MPS1 kinase inhibitors
Caldarelli, Marina
Angiolini, Mauro
Disingrini, Teresa
Donati, Daniele
Guanci, Marco
Nuvoloni, Stefano
Posteri, Helena
Quartieri, Francesca
Silvagni, Marco
Colombo, Riccardo
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (15) : 4507 - 4511
[7] Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex
Hewitt, Laura
Tighe, Anthony
Santaguida, Stefano
White, Anne M.
Jones, Clifford D.
Musacchio, Andrea
Green, Stephen
Taylor, Stephen S.
[J]. JOURNAL OF CELL BIOLOGY, 2010, 190 (01) : 25 - 34
[8] Phosphorylation sites in BubR1 that regulate kinetochore attachment, tension, and mitotic exit
Huang, Haomin
Hittle, James
Zappacosta, Francesca
Annan, Roland S.
Hershko, Avram
Yen, Timothy J.
[J]. JOURNAL OF CELL BIOLOGY, 2008, 183 (04) : 667 - 680
[9] Mps1 phosphorylates borealin to control aurora B activity and chromosome alignment
Jelluma, Nannette
Brenkman, Arjan B.
van den Broek, Niels J. F.
Cruijsen, Carin W. A.
van Osch, Maria H. J.
Lens, Susanne M. A.
Medema, Rene H.
Kops, Geert J. P. L.
[J]. CELL, 2008, 132 (02) : 233 - 246
[10] Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors
Kumar, D. Vijay
Hoarau, Christophe
Bursavich, Matthew
Slattum, Paul
Gerrish, David
Yager, Kraig
Saunders, Michael
Shenderovich, Mark
Roth, Bruce L.
McKinnon, Rena
Chan, Ashley
Cimbora, Daniel M.
Bradford, Chad
Reeves, Leslie
Patton, Scott
Papac, Damon I.
Williams, Brandi L.
Carlson, Robert O.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (13) : 4377 - 4385

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