2oo8: Difference between revisions

Revision as of 11:18, 4 May 2008

Synthesis, Structural Analysis, and SAR Studies of Triazine Derivatives as Potent, Selective Tie-2 Inhibitors

OverviewOverview

A novel class of selective Tie-2 inhibitors was derived from a multi-kinase inhibitor 1. By reversing the amide connectivity and incorporating aminotriazine or aminopyridine hinge-binding moieties, excellent Tie-2 potency and KDR selectivity could be achieved with 3-substituted terminal aryl rings. X-ray co-crystal structure analysis aided inhibitor design. This series was evaluated on the basis of potency, selectivity, and rat pharmacokinetic parameters.

About this StructureAbout this Structure

2OO8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors., Hodous BL, Geuns-Meyer SD, Hughes PE, Albrecht BK, Bellon S, Caenepeel S, Cee VJ, Chaffee SC, Emery M, Fretland J, Gallant P, Gu Y, Johnson RE, Kim JL, Long AM, Morrison M, Olivieri PR, Patel VF, Polverino A, Rose P, Wang L, Zhao H, Bioorg Med Chem Lett. 2007 May 15;17(10):2886-9. Epub 2007 Feb 25. PMID:17350837 Page seeded by OCA on Sun May 4 11:18:56 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2oo8.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2oo8 |SIZE=350|CAPTION= <scene name='initialview01'>2oo8</scene>, resolution 2.20&Aring;
+The line below this paragraph, containing "STRUCTURE_2oo8", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=RAJ:N-{3-[3-(DIMETHYLAMINO)PROPYL]-5-(TRIFLUOROMETHYL)PHENYL}-4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]BENZAMIDE'>RAJ</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= TEK, TIE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2oo8|  PDB=2oo8  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oo8 OCA], [http://www.ebi.ac.uk/pdbsum/2oo8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2oo8 RCSB]</span>
-}}
 '''Synthesis, Structural Analysis, and SAR Studies of Triazine Derivatives as Potent, Selective Tie-2 Inhibitors'''
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 [[Category: Bellon, S F.]]
 [[Category: Kim, J.]]
-[[Category: kinase]]
+[[Category: Kinase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 11:18:56 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:20:43 2008''