Abstract
2-Amino-3-piperidin-4-yl-propionic acid containing peptidomimetics are potent protease inhibitors when combined with an appropriate keto-thiazole or keto-carboxylic acid moiety. A novel P1 residue in factor Xa and thrombin inhibitors has been found resulting in IC50 values as low as 0.048 microM, a factor of ten more potent than Argatroban. Starting with non-chiral synthetic routes, a new stereospecific route was developed as well as a new solid-phase method.
MeSH terms
-
Blood Coagulation Factors / antagonists & inhibitors*
-
Blood Coagulation Factors / chemical synthesis*
-
Carboxylic Acids / chemistry
-
Factor Xa Inhibitors
-
Inhibitory Concentration 50
-
Kinetics
-
Models, Chemical
-
Piperidines / chemistry*
-
Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
-
Thiazoles / chemistry
-
Thrombin / antagonists & inhibitors
Substances
-
Blood Coagulation Factors
-
Carboxylic Acids
-
Factor Xa Inhibitors
-
Piperidines
-
Platelet Glycoprotein GPIIb-IIIa Complex
-
Thiazoles
-
piperidine
-
Thrombin