Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position.
Thrombin inhibitors incorporating o-aminoalkylbenzylamides in the P1 position were designed, synthesized and found to have enhanced potency and selectivity in several different structural classes. X-ray crystallographic analysis of compound 24 bound in the alpha-thrombin-hirugen complex provides an explanation for these unanticipated results.
D000577:Amides / Q000737:chemistry*; D000991:Antithrombins / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015394:Molecular Structure
D000577:Amides; D000991:Antithrombins