Summary
PDB 2J94 deposited: 2006-11-02 modified: 2009-02-24
Title CRYSTAL STRUCTURE OF A HUMAN FACTOR XA INHIBITOR COMPLEX
Authors Borthwick, A.D., Brown, D., Burns-Kurtis, C.L., Campbell, M., Chan, C., Chaudry, L., Chung, C.W., Convery, M.A., Hamblin, J.N., Johnstone, L., Kelly, H.A., Kleanthous, S., Patel, C., Pateman, A.J., Patikis, A., Senger, S., Shah, G.P., Toomey, J.R., Watson, N.S., Weston, H.E., Whitworth, C., Young, R.J., Zhou, P.
Method X-RAY DIFFRACTION
Structure factors resolution 2.1 rfactor 0.181 rfree 0.233
DPI 0.51 theoretical min: 0.21
Related PDB Entries 2J34 2J38 2J95 4Y71 4Y76 4Y79 4Y7A 4Y7B
Citations

Factor Xa inhibitory activities for a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides with different P1 groups are described. These data provide insight into binding interactions within the S1 primary specificity pocket; rationales are presented for the derived SAR on the basis of electronic interactions through crystal structures of fXa-ligand complexes and molecular modeling studies. A good correlation between in vitro anticoagulant activities with lipophilicity and the extent of human serum albumin binding is observed within this series of potent fXa inhibitors. Pharmacokinetic profiles in rat and dog, together with selectivity over other trypsin-like serine proteases, identified 1f as a candidate for further evaluation.

J. Med. Chem. 2007 Apr; 50(7):1546-1557 doi:10.1021/jm060870c

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1142976
PubMed 17338508 JMCMAR
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
2J94/1 2J94 1 dimer 0 2 2 2177