2p93: Difference between revisions
New page: left|200px<br /> <applet load="2p93" size="450" color="white" frame="true" align="right" spinBox="true" caption="2p93, resolution 1.90Å" /> '''Factor xa in comple... |
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[[Image:2p93. | [[Image:2p93.jpg|left|200px]]<br /><applet load="2p93" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2p93, resolution 1.90Å" /> | caption="2p93, resolution 1.90Å" /> | ||
'''Factor xa in complex with the inhibitor 5-chloro-N-(2-(4-(2-oxopyridin-1(2H)-yl)benzamido)ethyl)thiophene-2-carboxamide'''<br /> | '''Factor xa in complex with the inhibitor 5-chloro-N-(2-(4-(2-oxopyridin-1(2H)-yl)benzamido)ethyl)thiophene-2-carboxamide'''<br /> | ||
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==Overview== | ==Overview== | ||
In the search of Factor Xa (FXa) inhibitors structurally different from, the pyrazole-based series, we identified a viable series of enantiopure, cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective, inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide, 9 were the most potent neutral compounds, and had good anticoagulant, activity comparable to the pyrazole-based analogs. Crystal structures of, 7-FXa and 9-FXa illustrate binding similarities and differences between, the five- and the six-membered core systems, and provide rationales for, the observed SAR of P1 and linker moieties. | In the search of Factor Xa (FXa) inhibitors structurally different from, the pyrazole-based series, we identified a viable series of enantiopure, cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective, inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide, 9 were the most potent neutral compounds, and had good anticoagulant, activity comparable to the pyrazole-based analogs. Crystal structures of, 7-FXa and 9-FXa illustrate binding similarities and differences between, the five- and the six-membered core systems, and provide rationales for, the observed SAR of P1 and linker moieties. | ||
==About this Structure== | ==About this Structure== | ||
2P93 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ME1 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Full crystallographic information is available from [http:// | 2P93 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ME1:'>ME1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P93 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:26:10 2008'' | ||
Revision as of 15:26, 23 January 2008
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Factor xa in complex with the inhibitor 5-chloro-N-(2-(4-(2-oxopyridin-1(2H)-yl)benzamido)ethyl)thiophene-2-carboxamide
OverviewOverview
In the search of Factor Xa (FXa) inhibitors structurally different from, the pyrazole-based series, we identified a viable series of enantiopure, cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective, inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide, 9 were the most potent neutral compounds, and had good anticoagulant, activity comparable to the pyrazole-based analogs. Crystal structures of, 7-FXa and 9-FXa illustrate binding similarities and differences between, the five- and the six-membered core systems, and provide rationales for, the observed SAR of P1 and linker moieties.
About this StructureAbout this Structure
2P93 is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Coagulation factor Xa, with EC number 3.4.21.6 Full crystallographic information is available from OCA.
ReferenceReference
SAR and X-ray structures of enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and cyclohexyldiamine derivatives as inhibitors of coagulation Factor Xa., Qiao JX, Chang CH, Cheney DL, Morin PE, Wang GZ, King SR, Wang TC, Rendina AR, Luettgen JM, Knabb RM, Wexler RR, Lam PY, Bioorg Med Chem Lett. 2007 Aug 15;17(16):4419-27. Epub 2007 Jun 10. PMID:17588746
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