3Q3K

Factor Xa in complex with a phenylenediamine derivative

Summary for 3Q3K

• Entry DOI: 10.2210/pdb3q3k/pdb
• Related: 1V3X 1WU1 2EI6 2EI7 2EI8 3IIT
• Descriptor: Activated factor Xa heavy chain, Factor X light chain, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: protein inhibitor complex, blood coaggulation, cleavage of basic residues, disulfide bond, egf-like domain, hydroxylation, protease, secreted, zymogen, glycoprotein, hydrolase, blood coaggulation factor, serine protease, gamma-carboxyglutamic acid, plasma, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P00742 P00742
• Total number of polymer chains: 2
• Total formula weight: 32739.64

Authors

Suzuki, M.,Imai, E. (deposition date: 2010-12-22, release date: 2011-12-28, Last modification date: 2024-10-16)

Primary citation

Yoshikawa, K.,Yoshino, T.,Yokomizo, Y.,Uoto, K.,Naito, H.,Kawakami, K.,Mochizuki, A.,Nagata, T.,Suzuki, M.,Kanno, H.,Takemura, M.,Ohta, T.
Design, synthesis and SAR of novel ethylenediamine and phenylenediamine derivatives as factor Xa inhibitors.
Bioorg.Med.Chem.Lett., 21:2133-2140, 2011

PubMed Abstract: We previously reported on a series of cyclohexanediamine derivatives as highly potent factor Xa inhibitors. Herein, we describe the modification of the spacer moiety to discover an alternative scaffold. Ethylenediamine derivatives possessing a substituent at the C1 position in S configuration and phenylenediamine derivatives possessing a substituent at the C5 position demonstrated moderate to strong anti-fXa activity. Further SAR studies led to the identification of compound 30 h which showed both good in vitro activity (fXa IC(50) = 2.2 nM, PTCT2 = 3.9 μM) and in vivo antithrombotic efficacy.

PubMed: 21345673
DOI: 10.1016/j.bmcl.2011.01.132

Experimental method

X-RAY DIFFRACTION (2 Å)