Novel bicyclic lactam inhibitors of thrombin: potency and selectivity optimization through P1 residues
S Lévesque1, Y St-Denis, B Bachand
1Shire BioChem Inc., 275 Armand-Frappier Blvd., Laval, H7V 4A7, Québec, Canada. slevesque@ca.shire.com
Bioorganic & Medicinal Chemistry Letters
|November 27, 2001
Abstract:
Peptidomimetic inhibitors of thrombin lacking the important Ser195-carbonyl interaction have been prepared. The binding energy lost after the removal of the activated carbonyl was recaptured through a series of modifications of the P1 residues of the bicyclic lactam inhibitors. Selected substituted compounds displayed useful pharmacological profiles both in vitro and in vivo.


