2a2x: Difference between revisions
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==Overview== | ==Overview== | ||
Synthesis and SAR of orally active thrombin inhibitors of the | 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. | ||
==Disease== | ==Disease== | ||
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[[Category: Thrombin]] | [[Category: Thrombin]] | ||
[[Category: Baucke, D.]] | [[Category: Baucke, D.]] | ||
[[Category: Hoeffken, H | [[Category: Hoeffken, H W.]] | ||
[[Category: Hornberger, W.]] | [[Category: Hornberger, W.]] | ||
[[Category: Lange, U | [[Category: Lange, U E.W.]] | ||
[[Category: Mack, H.]] | [[Category: Mack, H.]] | ||
[[Category: Seitz, W.]] | [[Category: Seitz, W.]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:23:03 2008'' | ||
Revision as of 17:23, 21 February 2008
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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.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
2A2X is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Thrombin, with EC number 3.4.21.5 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 Thu Feb 21 16:23:03 2008