Solution-phase and solid-phase synthesis of novel transition state inhibitors of coagulation enzymes incorporating a
A E Adang1, A M Peters, S Gerritsma
1Lead Discovery Unit, Research and Development, NV Organon, Oss, The Netherlands.
Bioorganic & Medicinal Chemistry Letters
|May 26, 1999
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.
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