PDB 2G00 deposited: 2006-02-10 modified: 2009-02-24
Title 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
Authors Alexander, R.S., Clark, C., Galemmo, R.A., He, K., Knabb, R.M., Lam, P.Y., Li, R., Luettgen, J.M., Orwat, M.J., Pinto, D.J., Quan, M.L., Rendina, A.R., Rossi, K.A., Smallwood, A., Wells, B., Wexler, R.R., Woerner, F., Wong, P.C.
Structure factors resolution 2.1 rfactor 0.269 rfree 0.284
DPI 0.58 theoretical min: 0.26

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.

Bioorg.Med.Chem.Lett. 2006 Nov; 16(21):5584-5589 doi:10.1016/j.bmcl.2006.08.027

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1139730
PubMed 16963264 BMCLE8
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
2G00/1 2G00 1 dimer 0 2 1 2076