Discovery of imidazole vinyl pyrimidines as a novel class of kinase inhibitors which inhibit Tie-2 and are orally bioavailable

被引：7

作者：

Buttar, David ^{[1
]}

Edge, Mike ^{[1
]}

Emery, Steve C. ^{[1
]}

Fitzek, Martina ^{[1
]}

Forder, Cheryl ^{[1
]}

Griffen, Alison ^{[1
]}

Hayter, Barry ^{[1
]}

Hayward, Chris F. ^{[1
]}

Hopcroft, Philip J. ^{[1
]}

Luke, Richard W. A. ^{[1
]}

Page, Ken ^{[1
]}

Stawpert, John ^{[1
]}

Wright, Andy ^{[1
]}

机构：

[1] AstraZeneca, Canc & Infect Res Area, Mereside, Macclesfield SK10 4TG, Cheshire, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 16期

关键词：

angiogenesis; kinase; Tie-2; inhibitor; pyrimidine; imidazole; alkene;

D O I：

10.1016/j.bmcl.2008.06.106

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Tie-2 is a receptor tyrosine kinase which is involved in angiogenesis and thereby growth of human tumours. The discovery and SAR of a novel class of imidazole-vinyl-pyrimidine kinase inhibitors, which inhibit Tie-2 in vitro is reported. Their synthesis was carried out by condensation of imidazole aldehydes with methyl pyrimidines. These compounds are lead-like, with low molecular weight, good physical properties and oral bioavailability. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4723 / 4726

页数：4

共 50 条

[1] Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase
Cee, Victor J.
Cheng, Alan C.
Romero, Karina
Bellon, Steve
Mohr, Christopher
Whittington, Douglas A.
Bak, Annette
Bready, James
Caenepeel, Sean
Coxon, Angela
Deak, Holly L.
Fretland, Jenne
Gu, Yan
Hodous, Brian L.
Huang, Xin
Kim, Joseph L.
Lin, Jasmine
Long, Alexander M.
Nguyen, Hanh
Olivieri, Philip R.
Patel, Vinod F.
Wang, Ling
Zhou, Yihong
Hughes, Paul
Geuns-Meyer, Stephanie
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (02) : 424 - 427
[2] MEDI 370-Evolution of selective, potent, and orally bioavailable small molecule Tie-2 kinase inhibitors
Olivieri, Philip R., II
Geuns-Meyer, Stephanie D.
Hughes, Paul E.
Albrecht, Brian K.
Bellon, Steve
Bready, James
Caenepeel, Sean
Cee, Victor J.
Chaffee, Stuart C.
Coxon, Angela
Emery, Maurice
Fretland, Jenne
Gallant, Paul
Gu, Yan
Hodous, Brian L.
Hoffman, Doug
Johnson, Rebecca E.
Kendall, Richard
Kim, Joseph L.
Long, Alexander M.
Morrison, Michael
Patel, Vinod F.
Polverino, Anthony
Rose, Paul
Tempest, Paul
Wang, Ling
Whittington, Douglas A.
Zhao, Huilin
[J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2007, 234
[3] Discovery of a novel, selective, and orally bioavailable class of aggrecanase inhibitors.
Yao, WQ
Chao, M
Reddy, G
Shi, E
Arner, EC
Pratta, MA
Covington, MB
Tortorella, MD
Magolda, RL
Wasserman, ZR
Wexler, RR
Decicco, CP
[J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2000, 220 : U566 - U566
[4] Discovery of novel Benzimidazoles as potent inhibitors of TIE-2 and VEGFR-2 tyrosine kinase receptors
Hasegawa, Masaichi
Nishigaki, Naohiko
Washio, Yoshiaki
Kano, Kazuya
Harris, Philip A.
Sato, Hideyuki
Mori, Ichiro
West, Rob I.
Shibahara, Megumi
Toyoda, Hiroko
Wang, Liping
Nolte, Robert T.
Veal, James M.
Cheung, Mui
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (18) : 4453 - 4470
[5] Alkynylpyrimidine amide derivatives as potent, selective, and orally active inhibitors of tie-2 kinase
Cee, Victor J.
Albrecht, Brian K.
Geuns-Meyer, Stephanie
Hughes, Paul
Bellon, Steve
Bready, James
Caenepeel, Sean
Chaffee, Stuart C.
Coxon, Angela
Emery, Maurice
Fretland, Jenne
Gallant, Paul
Gu, Yan
Hodous, Brian L.
Hoffman, Doug
Johnson, Rebecca E.
Kendall, Richard
Kim, Joseph L.
Long, Alexander M.
McGowan, David
Morrison, Michael
Olivieri, Philip R.
Patel, Vinod F.
Polverino, Anthony
Powers, David
Rose, Paul
Wang, Ling
Zhao, Huilin
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (04) : 627 - 640
[6] Discovery and synthesis of novel 4-aminopyrrolopyrimidine Tie-2 kinase inhibitors for the treatment of solid tumors
Arcari, Joel T.
Beebe, Jean S.
Berliner, Martin A.
Bernardo, Vincent
Boehm, Merin
Borzillo, Gary V.
Clark, Tracey
Cohen, Bruce D.
Connell, Richard D.
Frost, Heather N.
Gordon, Deborah A.
Hungerford, William M.
Kakar, Shefali M.
Kanter, Aaron
Keene, Nandell F.
Knauth, Elizabeth A.
LaGreca, Susan D.
Lu, Yong
Martinez-Alsina, Louis
Marx, Matthew A.
Morris, Joel
Patel, Nandini C.
Savage, Doug
Soderstrom, Cathy I.
Thompson, Carl
Tkalcevic, George
Tom, Norma J.
Vajdos, Felix F.
Valentine, James J.
Vincent, Patrick W.
Wessel, Matthew D.
Chen, Jinshan M.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (10) : 3059 - 3063
[7] Discovery of a Novel Series of Potent and Orally Bioavailable Phosphoinositide 3-Kinase γ Inhibitors
Leahy, James W.
Buhr, Chris A.
Johnson, Henry W. B.
Kim, Byung Gyu
Baik, TaeGon
Cannoy, Jonah
Forsyth, Timothy P.
Jeong, Joon Won
Lee, Matthew S.
Ma, Sunghoon
Noson, Kevin
Wang, Longcheng
Williams, Matthew
Nuss, John M.
Brooks, Eric
Foster, Paul
Goon, Leanne
Heald, Nathan
Holst, Charles
Jaeger, Christopher
Lam, Scott
Lougheed, Julie
Lam Nguyen
Plonowski, Arthur
Song, Joanne
Stout, Thomas
Wu, Xiang
Yakes, Michael F.
Yu, Peiwen
Zhang, Wentao
Lamb, Peter
Raeber, Olivia
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (11) : 5467 - 5482
[8] CEP-11981: Identification of an orally bioavailable TIE-2/VEGF-R2 inhibitor with broad kinase inhibitory activity
Underiner, Theodore L.
Aimone, Lisa
Albom, Mark
Angeles, Thelma
Ator, Mark
Bacon, Ed
Becknell, Nadine
Hudkins, Robert L.
Jacobs, Marty
Learn, Keith S.
Mallamo, John
Meyer, Sherri
Park, Chung Ho
Pauletti, Dan
Reddy, Dandu
Rolon-Steele, Damaris
Ruggeri, Bruce A.
Spais, Chrysanthe
Tao, Ming
Wagner, Jason
Weinberg, Linda
Yang, Shi
Zulli, Allison
McCort, Gary
[J]. MOLECULAR CANCER THERAPEUTICS, 2007, 6 (12) : 3593S - 3593S
[9] The Discovery and Optimization of a Novel Class of Potent, Selective, and Orally Bioavailable Anaplastic Lymphoma Kinase (ALK) Inhibitors with Potential Utility for the Treatment of Cancer
Lewis, Richard T.
Bode, Christiane M.
Choquette, Deborah M.
Potashman, Michele
Romero, Karina
Stellwagen, John C.
Teffera, Yohannes
Moore, Earl
Whittington, Douglas A.
Chen, Hao
Epstein, Linda F.
Emkey, Renee
Andrews, Paul S.
Yu, Violeta L.
Saffran, Douglas C.
Xu, Man
Drew, Allison
Merkel, Patricia
Szilvassy, Steven
Brake, Rachael L.
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (14) : 6523 - 6540
[10] MEDI 102-Synthetic approaches to novel analogs of Tie-2 kinase inhibitors
Arcari, Joel T.
Chen, Michael J.
Hungerford, William
Patel, Nandini
Marx, Matthew A.
LaGreca, Susan
Martinez-Alsina, Luis
Wessel, Matthew
Anderson, Stephen
Bordner, Jon
Borzillo, Gary
Clark, Tracey
Cohen, Bruce
Ewing, Marcus
Soderstrom, Catherine
Kakar, Shefali
Kanter, Aaron
Knauth, Lissie
Thompson, Carl
Tom, Norma
Samardjiev, Ivan
Vincent, Patrick W.
[J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2006, 232

← 1 2 3 4 5 →