Pyridine derivatives and their use in the treatment of conditions associated with pathological thrombus formation

摘要

The present invention relates to compounds of the formula (I), wherein the residues R1 to R6, V, G and M have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds for use in the treatment of diverse disorders, for example cardiovascular disorders like thromboembolic diseases or restenoses. The compounds of the invention are effective antagonists of the platelet LPA receptor LPAR5 (GPR92) and can in general be applied in conditions in which an undesired activation of the platelet LPA receptor LPAR5, the mast cell LPA receptor LPAR5 or the microglia cell LPA receptor LPAR5 is present, or for the cure or prevention of which an inhibition of the platelet, mast cell or microglia cell LPA receptor LPAR5 is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in medicaments, and pharmaceutical compositions comprising them.;

主权项

1. A compound of the formula I,wherein
R1 and R2 are independently of each other selected from the series consisting of (C1-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl-, Ar and Ar—(C1-C4)-alkyl-; R3 and R4 are independently of each other selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl-, Ar and Ar—(C1-C4)-alkyl-; R5 and R6 are independently of each other selected from the series consisting of hydrogen, fluorine and (C1-C6)-alkyl, or R5 and R6 together with the carbon atom carrying them form a (C3-C7)-cycloalkane ring which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl; R11, R12, R13 and R14 are independently of each other selected from the series consisting of hydrogen and (C1-C4)-alkyl; Ar is selected from the series consisting of phenyl, naphthyl and an aromatic, 5-membered or 6-membered, monocyclic heterocycle which comprises one or two identical or different ring heteroatoms selected from N, O and S, which are all unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (C1-C4)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl-, cyano and (C1-C4)-alkyl-O—; V is selected from the series consisting of R11—O—and R12—N(R13—, and G and M are not present, or V is selected from the series consisting of —N(R14)—, —N(R14)—(C1-C4)-alkyl-, —O— and —O—(C1 -C4)-alkyl- , and G is selected from the series consisting of a direct bond and phenylene which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (C1-C4)-alkyl, cyano and (C1-C4)-alkyl- O—,
provided that G is not a direct bond if V is —N(R14)— or —O—, and M is selected from the series consisting of R11—O—C(O)— and R12—N(R13)—C(O)—; wherein all alkyl groups are unsubstituted or substituted by one or more fluorine substituents, and all cycloalkyl groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl; in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof.