2R2M: 2-(2-chloro-6-fluorophenyl)acetamides As Potent Thrombin Inhibitors

Citation:
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.
PDB ID: 2R2MDownload
MMDB ID: 66254
PDB Deposition Date: 2007/8/27
Updated in MMDB: 2008/09
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 2R2M: trimeric; determined by author
Molecular Components in 2R2M
Label Count Molecule
Proteins (3 molecules)
1
Thrombin Light Chain(Gene symbol: F2)
Molecule annotation
1
Thrombin Heavy Chain(Gene symbol: F2)
Molecule annotation
1
Hirudin-3a
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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