2G00

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

Summary for 2G00

• Entry DOI: 10.2210/pdb2g00/pdb
• Descriptor: Coagulation factor X, 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 (3 entities in total)
• Functional Keywords: glycoprotein, hydrolase, serine protease, plasma, blood coagulation factor, protein inhibitor complex, calcium-binding
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P00742 P00742
• Total number of polymer chains: 2
• Total formula weight: 32569.88

Authors

Alexander, R.S. (deposition date: 2006-02-10, release date: 2006-10-03, Last modification date: 2024-10-30)

Primary citation

Pinto, D.J.,Galemmo, R.A.,Quan, M.L.,Orwat, M.J.,Clark, C.,Li, R.,Wells, B.,Woerner, F.,Alexander, R.S.,Rossi, K.A.,Smallwood, A.,Wong, P.C.,Luettgen, J.M.,Rendina, A.R.,Knabb, R.M.,He, K.,Wexler, R.R.,Lam, P.Y.
Discovery of potent, efficacious, and orally bioavailable inhibitors of blood coagulation factor Xa with neutral P1 moieties.
Bioorg.Med.Chem.Lett., 16:5584-5589, 2006

PubMed Abstract: 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.

PubMed: 16963264
DOI: 10.1016/j.bmcl.2006.08.027

Experimental method

X-RAY DIFFRACTION (2.1 Å)