2P93

Factor xa in complex with the inhibitor 5-chloro-N-(2-(4-(2-oxopyridin-1(2H)-yl)benzamido)ethyl)thiophene-2-carboxamide

Summary for 2P93

• Entry DOI: 10.2210/pdb2p93/pdb
• Related: 2P94 2P95
• Descriptor: Factor Xa, 5-CHLORO-N-(2-(4-(2-OXOPYRIDIN-1(2H)-YL)BENZAMIDO)ETHYL)THIOPHENE-2-CARBOXAMIDE, ... (4 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: 32438.20

Authors

Chang, C.-H. (deposition date: 2007-03-23, release date: 2007-07-24, Last modification date: 2024-10-30)

Primary citation

Qiao, J.X.,Chang, C.-H.,Cheney, D.L.,Morin, P.E.,Wang, G.Z.,King, S.R.,Wang, T.C.,Rendina, A.R.,Luettgen, J.M.,Knabb, R.M.,Wexler, R.R.,Lam, P.Y.S.
SAR and X-ray structures of enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and cyclohexyldiamine derivatives as inhibitors of coagulation Factor Xa
Bioorg.Med.Chem.Lett., 17:4419-4427, 2007

PubMed Abstract: 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.

PubMed: 17588746
DOI: 10.1016/j.bmcl.2007.06.029

Experimental method

X-RAY DIFFRACTION (1.9 Å)