Title of article :
Small, low nanomolar, noncovalent thrombin inhibitors lacking a group to fill the ‘Distal binding pocket’
Author/Authors :
Philip E. J. Sanderson، نويسنده , , Kellie J. Cutrona، نويسنده , , Dona L. Dyer، نويسنده , , Julie A. Krueger، نويسنده , , Lawrence C. Kuo، نويسنده , , S. Dale Lewis، نويسنده , , Bobby J. Lucas Jr.، نويسنده , , Youwei Yan، نويسنده ,
Abstract :
Use of a chlorophenoxyacetamide P1 group with a pyridinone acetamide P2/P3 gave an exceptionally potent thrombin inhibitor (Ki=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 thrombinʹs ‘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.
