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

…, S Gerritsma, E de Zwart, G Veeneman

Index: Adang, Anton E. P.; Peters, Co A. M.; Gerritsma, Siene; De Zwart, Edwin; Veeneman, Gerrit Bioorganic and Medicinal Chemistry Letters, 1999 , vol. 9, # 9 p. 1227 - 1232

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Citation Number: 13

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 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- ...