2a2x: Difference between revisions

Revision as of 18:32, 3 May 2008

Orally Active Thrombin Inhibitors in Complex with Thrombin Inh12

OverviewOverview

Synthesis and SAR of orally active thrombin inhibitors of the d-Phe-Pro-Arg type with focus on the P2-moiety are described. The unexpected increase in in vitro potency, oral bioavailability, and in vivo activity of inhibitors with dehydroproline as P2-isostere is discussed. Over a period of 24h the antithrombin activity of the most active inhibitors with IC(50)s in the nanomolar range was determined in dogs demonstrating high thrombin inhibitory activity in plasma and an appropriate duration of action after oral administration.

About this StructureAbout this Structure

2A2X is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Orally active thrombin inhibitors. Part 2: optimization of the P2-moiety., Lange UE, Baucke D, Hornberger W, Mack H, Seitz W, Hoffken HW, Bioorg Med Chem Lett. 2006 May 15;16(10):2648-53. Epub 2006 Feb 3. PMID:16460939 Page seeded by OCA on Sat May 3 18:32:07 2008

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

OCA

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 [[Image:2a2x.jpg|left|200px]]
- {{Structure
+<!--
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+The line below this paragraph, containing "STRUCTURE_2a2x", 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=ALC:2-AMINO-3-CYCLOHEXYL-PROPIONIC+ACID'>ALC</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=NA9:N-(CARBOXYMETHYL)-3-CYCLOHEXYL-D-ALANYL-N-({6-[AMINO(IMINO)METHYL]PYRIDIN-3-YL}METHYL)-N~2~-METHYL-L-ALANINAMIDE'>NA9</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=SMF:4-SULFOMETHYL-L-PHENYLALANINE'>SMF</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/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2a2x|  PDB=2a2x  |  SCENE=  }}
-|RELATEDENTRY=[[2ank|2ANK]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a2x OCA], [http://www.ebi.ac.uk/pdbsum/2a2x PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a2x RCSB]</span>
-}}
 '''Orally Active Thrombin Inhibitors in Complex with Thrombin Inh12'''
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 [[Category: Mack, H.]]
 [[Category: Seitz, W.]]
-[[Category: blood clotting]]
+[[Category: Blood clotting]]
-[[Category: serine protease,]]
+[[Category: Serine protease]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:32:07 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:47:05 2008''