2R2M

2-(2-Chloro-6-Fluorophenyl)Acetamides as Potent Thrombin Inhibitors

2R2M の概要

• エントリーDOI: 10.2210/pdb2r2m/pdb
• 分子名称: Thrombin light chain, Thrombin heavy chain, Hirudin-3A, ... (5 entities in total)
• 機能のキーワード: thrombin, acute phase, blood coagulation, cleavage on pair of basic residues, disease mutation, gamma-carboxyglutamic acid, glycoprotein, kringle, protease, secreted, serine protease, zymogen, protease inhibitor, serine protease inhibitor, sulfation, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space: P00734 P00734; Secreted: P28507
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 34711.00

構造登録者

Spurlino, J. (登録日: 2007-08-27, 公開日: 2008-08-26, 最終更新日: 2024-10-30)

主引用文献

Lee, L.,Kreutter, K.D.,Pan, W.,Crysler, C.,Spurlino, J.,Player, M.R.,Tomczuk, B.,Lu, T.
2-(2-Chloro-6-Fluorophenyl)Acetamides as Potent Thrombin Inhibitors
Bioorg.Med.Chem.Lett., 17:6266-6269, 2007

PubMed Abstract: 2-(2-Chloro-6-fluorophenyl)acetamides having 2,2-difluoro-2-aryl/heteroaryl-ethylamine P3 and oxyguanidine P1 substituents are potent thrombin inhibitors (K(i)=0.9-33.9 nM). 2-(5-Chloro-pyridin-2-yl)-2,2-difluoroethylamine was the best P3 substituent, yielding the most potent inhibitor (K(i)=0.7 nM). Replacing the P3 heteroaryl group with a phenyl ring or replacing the difluoro substitution with dimethyl or cyclopropyl groups in the linker reduced the affinity for thrombin significantly. The aminopyridine P1s also provided an increase in potency.

PubMed: 17889527
DOI: 10.1016/j.bmcl.2007.09.013

実験手法

X-RAY DIFFRACTION (2.1 Å)