Solution-phase and solid-phase synthesis of novel transition state inhibitors of coagulation enzymes incorporating a piperidinyl moiety

Article abstract of DOI:10.1016/S0960-894X(99)00179-1

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 μM, 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.