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