1zgi
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | Thrombin-inhibitor X-ray crystal structures, in combination with the | + | Thrombin-inhibitor X-ray crystal structures, in combination with the installation of binding elements optimized within the pyrazinone series of thrombin inhibitors, were utilized to transform a weak triazolopyrimidine lead into a series of potent oxazolopyridines. A modification intended to attenuate plasma protein binding (i.e., conversion of the P3 pyridine to a piperidine) conferred significant factor Xa activity to this series. Ultimately, these dual thrombin/factor Xa inhibitors demonstrated excellent in vitro and in vivo anticoagulant efficacy. |
==Disease== | ==Disease== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
| - | [[Category: Burgey, C | + | [[Category: Burgey, C S.]] |
| - | [[Category: Coburn, C | + | [[Category: Coburn, C A.]] |
| - | [[Category: Deng, J | + | [[Category: Deng, J Z.]] |
| - | [[Category: Krueger, J | + | [[Category: Krueger, J A.]] |
| - | [[Category: Kuo, L | + | [[Category: Kuo, L C.]] |
| - | [[Category: Lewis, S | + | [[Category: Lewis, S D.]] |
| - | [[Category: Lucas, B | + | [[Category: Lucas, B J.]] |
| - | [[Category: Lyle, T | + | [[Category: Lyle, T A.]] |
| - | [[Category: McMasters, D | + | [[Category: McMasters, D R.]] |
| - | [[Category: Rabbat, P | + | [[Category: Rabbat, P M.]] |
[[Category: Strulovici, B.]] | [[Category: Strulovici, B.]] | ||
| - | [[Category: Vacca, J | + | [[Category: Vacca, J P.]] |
| - | [[Category: Williams, P | + | [[Category: Williams, P D.]] |
[[Category: Yan, Y.]] | [[Category: Yan, Y.]] | ||
[[Category: 382]] | [[Category: 382]] | ||
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[[Category: thrombin inhibitor complex]] | [[Category: thrombin inhibitor complex]] | ||
| - | ''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 16:15:18 2008'' |
Revision as of 14:15, 21 February 2008
|
thrombin in complex with an oxazolopyridine inhibitor 21
Contents |
Overview
Thrombin-inhibitor X-ray crystal structures, in combination with the installation of binding elements optimized within the pyrazinone series of thrombin inhibitors, were utilized to transform a weak triazolopyrimidine lead into a series of potent oxazolopyridines. A modification intended to attenuate plasma protein binding (i.e., conversion of the P3 pyridine to a piperidine) conferred significant factor Xa activity to this series. Ultimately, these dual thrombin/factor Xa inhibitors demonstrated excellent in vitro and in vivo anticoagulant efficacy.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1ZGI 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.
Reference
Development of an oxazolopyridine series of dual thrombin/factor Xa inhibitors via structure-guided lead optimization., Deng JZ, McMasters DR, Rabbat PM, Williams PD, Coburn CA, Yan Y, Kuo LC, Lewis SD, Lucas BJ, Krueger JA, Strulovici B, Vacca JP, Lyle TA, Burgey CS, Bioorg Med Chem Lett. 2005 Oct 15;15(20):4411-6. PMID:16137886
Page seeded by OCA on Thu Feb 21 16:15:18 2008
