Macrocyclic Urea Derivatives as Inhibitors of TAFIa, Their Preparation and Their Use as Pharmaceuticals

摘要

The present invention relates to macrocydic urea derivatives of the formula I (I) in which R1, R2, R3, V and Y are as defined below. The compounds of the formula I are inhibitors of the enzyme TAFIa (activated thrombin-activatable fibrinolysis inhibitor). The invention further relates to the process for the preparation of the compounds of formula I and to the use thereof as medicaments.;

主权项

1. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, wherein V is —(C2-C9)-alkylene-; Y is a covalent bond or —(C6-C14)-aryl-,
wherein —(C6-C14)-aryl- is unsubstituted or substituted by one, two or three R15 groups; R1 is —(C1-C6)-alkyl, —(C0-C4)-alkylene-aryl or —(C0-C4)-alkylene-(C3-C8)-cycloalkyl,
wherein alkyl, —(C0-C4)-alkylene, aryl and —(C3-C8)-cycloalkyl are unsubstituted or substituted by one, two or three R16 groups; R2 is —(C1-C3)-alkyl; R3 is Het substituted by —NH2, or —(C3-C8)-cycloalky substituted by —NH2,
wherein Het is a 5-membered or 6-membered, monocyclic, aromatic heterocycle comprising 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, andwherein Het and —(C4-C8)-cycloalkyl are unsubstituted or substituted by one two or three R15 groups; each R15 group is independently hydrogen, —(C1-C4)-alkyl, —O—CF3, —NH2, —OH, —CF3 or halogen; and each R16 group is independently —O—CF3, —NH2, —OH, —CF3 or halogen.