Small, low nanomolar, noncovalent thrombin inhibitors lacking a group to fill the 'distal binding pocket'.
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Sanderson PE, Cutrona KJ, Dyer DL, Krueger JA, Kuo LC, Lewis SD, Lucas BJ, Yan Y
Small, low nanomolar, noncovalent thrombin inhibitors lacking a group to fill the 'distal binding pocket'.
Bioorg Med Chem Lett. 2003 Jan 20;13(2):161-4.
- PubMed ID
- 12482415 [ View in PubMed]
- Abstract
Use of a chlorophenoxyacetamide P1 group with a pyridinone acetamide P2/P3 gave an exceptionally potent thrombin inhibitor (K(i)=40 pM). Truncation of the molecule at the N-terminus gave unique, low nanomolar, non-covalent thrombin inhibitors which do not have a group to fill thrombin's 'distal binding pocket'. A co-crystal structure indicates the importance of an intramolecular hydrogen bond between the P1 side chain and P1/P2 amide link in this series.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 1-[2-AMINO-2-CYCLOHEXYL-ACETYL]-PYRROLIDINE-3-CARBOXYLIC ACID 5-CHLORO-2-(2-ETHYLCARBAMOYL-ETHOXY)-BENZYLAMIDE Prothrombin Ki (nM) 0.74 N/A N/A Details