2g00
From Proteopedia
| Line 5: | Line 5: | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=4QC:3-[6-{2'-[(DIMETHYLAMINO)METHYL]BIPHENYL-4-YL}-7-OXO-3-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDRO-1H-PYRAZOLO[3,4-C]PYRIDIN-1-YL]BENZAMIDE'>4QC</scene> | |LIGAND= <scene name='pdbligand=4QC:3-[6-{2'-[(DIMETHYLAMINO)METHYL]BIPHENYL-4-YL}-7-OXO-3-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDRO-1H-PYRAZOLO[3,4-C]PYRIDIN-1-YL]BENZAMIDE'>4QC</scene> | ||
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2g00 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g00 OCA], [http://www.ebi.ac.uk/pdbsum/2g00 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2g00 RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
The bicyclic dihydropyrazolopyridinone scaffold allowed for incorporation of multiple P1 moieties with subnanomolar binding affinities for blood coagulation factor Xa. The compound 3-[6-(2'-dimethylaminomethyl-biphenyl-4-yl)-7-oxo-3-trifluoro-methyl-4,5,6 ,7-tetrahydro-pyrazolo[3,4-c]pyridine-l-yl]-benzamide 6d shows good fXa potency, selectivity, in vivo efficacy and oral bioavailability. Compound 6d was selected for further pre-clinical evaluations. | The bicyclic dihydropyrazolopyridinone scaffold allowed for incorporation of multiple P1 moieties with subnanomolar binding affinities for blood coagulation factor Xa. The compound 3-[6-(2'-dimethylaminomethyl-biphenyl-4-yl)-7-oxo-3-trifluoro-methyl-4,5,6 ,7-tetrahydro-pyrazolo[3,4-c]pyridine-l-yl]-benzamide 6d shows good fXa potency, selectivity, in vivo efficacy and oral bioavailability. Compound 6d was selected for further pre-clinical evaluations. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Factor X deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227600 227600]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 27: | Line 27: | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Alexander, R S.]] | [[Category: Alexander, R S.]] | ||
| - | [[Category: 4QC]] | ||
[[Category: blood coagulation factor]] | [[Category: blood coagulation factor]] | ||
[[Category: calcium-binding]] | [[Category: calcium-binding]] | ||
| Line 36: | Line 35: | ||
[[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 Mon Mar 31 03:09:58 2008'' |
Revision as of 00:10, 31 March 2008
| |||||||
| , resolution 2.100Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Coagulation factor Xa, with EC number 3.4.21.6 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Factor Xa in complex with the inhibitor 3-(6-(2'-((dimethylamino)methyl)-4-biphenylyl)-7-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl)benzamide
Overview
The bicyclic dihydropyrazolopyridinone scaffold allowed for incorporation of multiple P1 moieties with subnanomolar binding affinities for blood coagulation factor Xa. The compound 3-[6-(2'-dimethylaminomethyl-biphenyl-4-yl)-7-oxo-3-trifluoro-methyl-4,5,6 ,7-tetrahydro-pyrazolo[3,4-c]pyridine-l-yl]-benzamide 6d shows good fXa potency, selectivity, in vivo efficacy and oral bioavailability. Compound 6d was selected for further pre-clinical evaluations.
About this Structure
2G00 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Discovery of potent, efficacious, and orally bioavailable inhibitors of blood coagulation factor Xa with neutral P1 moieties., Pinto DJ, Galemmo RA Jr, Quan ML, Orwat MJ, Clark C, Li R, Wells B, Woerner F, Alexander RS, Rossi KA, Smallwood A, Wong PC, Luettgen JM, Rendina AR, Knabb RM, He K, Wexler RR, Lam PY, Bioorg Med Chem Lett. 2006 Nov 1;16(21):5584-9. Epub 2006 Sep 11. PMID:16963264
Page seeded by OCA on Mon Mar 31 03:09:58 2008
