- MULTI-CYCLIC COMPOUNDS AND METHODS OF USE
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The present invention relates to compounds of Formulas I and II, wherein B1, B2, B3, B4, C1, C2, ring D, L1, L2 and R1-4 are defined herein, synthetic inter
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Page/Page column 34-35
(2008/12/05)
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- Alkynylpyrimidine amide derivatives as potent, selective, and orally active inhibitors of Tie-2 kinase
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The recognition that aberrant angiogenesis contributes to the pathology of inflammatory diseases, cancer, and myocardial ischemia has generated considerable interest in the molecular mechanisms that regulate blood vessel growth. The receptor tyrosine kinase Tie-2 is expressed primarily by vascular endothelial cells and is critical for embryonic vasculogenesis. Interference with the Tie-2 pathway by diverse blocking agents such as soluble Tie-2 receptors, anti-Tie-2 intrabodies, anti-Ang-2 antibodies, and peptide-F c conjugates has been shown to suppress tumor growth in xenograft studies. An alternative strategy for interfering with the Tie-2 signaling pathway involves direct inhibition of the kinase functions of the Tie-2 receptor. Herein we describe the development of alkynylpyrimidine amide derivatives as potent, selective, and orally available ATP-competitive inhibitors of Tie-2 autophosphorylation.
- 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
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p. 627 - 640
(2007/10/03)
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- Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine Tie-2 kinase inhibitor
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Inhibition of angiogenesis is a promising and clinically validated approach for limiting tumor growth and survival. The receptor tyrosine kinase Tie-2 is expressed almost exclusively in the vascular endothelium and is required for developmental angiogenes
- Hodous, Brian L.,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,Hoffman, Doug,Johnson, Rebecca E.,Kendall, Richard,Kim, Joseph L.,Long, Alexander M.,Morrison, Michael,Olivieri, Philip R.,Patel, Vinod F.,Polverino, Anthony,Rose, Paul,Tempest, Paul,Wang, Ling,Whittington, Douglas A.,Zhao, Huilin
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p. 611 - 626
(2007/10/03)
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