SUBSTITUTED BIPIPERIDINYL DERIVATIVES

摘要

The invention relates to novel substituted bipiperidinyl derivatives, to processes for their preparation, to their use for the treatment and/or prevention of diseases and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of diabetic microangiopathies, diabetic ulcers on the extremities, in particular for promoting wound healing of diabetic foot ulcers, diabetic heart failure, diabetic coronary microvascular heart disorders, peripheral and cardiac vascular disorders, thromboembolic disorders and ischaemias, peripheral circulatory disturbances, Raynaud's phenomenon, CREST syndrome, microcirculatory disturbances, intermittent claudication, and peripheral and autonomous neuropathies.

主权项

1. A compound of the formula (I) in which represents a single bond or a double bond, R1 is selected from the group consisting of C3-C6-alkyl, C1-C3-alkoxycarbonyl, oxetanyl, 5- or 6-membered heteroaryl, —(CR6R7)—R8 and —CONR9R10,
where oxetanyl may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of 3-hydroxy and 3-C1-C4-alkyl,andwhereR6 is selected from the group consisting of hydrogen, methyl and ethyl,R7 is selected from the group consisting of hydrogen, methyl and ethyl,orR6 and R7 together with the carbon atom to which they are attached form a cyclopropyl ring or cyclobutyl ring,R8 is selected from the group consisting of hydroxy, hydroxymethyl, C1-C4-alkyl, C1-C4-alkoxy, C1-C3-alkoxycarbonyl, C1-C4-alkylaminocarbonyl, phenoxy, oxetanyl, 5- or 6-membered heteroaryl and —CH2NR13R14,
where phenoxy and heteroaryl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of C1-C4-alkyl and C1-C4-alkoxy,where oxetanyl may be substituted by 1 or 2 substituents independently of one another selected from the group consisting of 3-C1-C4-alkyl and 3-OH,andwhereR13 is selected from the group consisting of hydrogen and C1-C4-alkyl,andR14 is selected from the group consisting of methyl, methylsulphonyl and formyl,R9 is selected from the group consisting of C1-C6-alkyl, C3-C6-cycloalkyl and 5- or 6-membered heteroaryl,
where heteroaryl may be substituted by C1-C4-alkyl,where alkyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of hydroxy, with the proviso that alkyl is C2-C6-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C3-C6-cycloalkyl, phenyl, oxetanyl and 5- or 6-membered heteroaryl,
in which this phenyl heteroaryl for its part may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and C1-C4-alkylin which this oxetanyl for its part may be substituted by one or 2 substituents selected from the group consisting of 3-C1-C4-alkyl and 3-hydroxyR10 is selected from the group consisting of hydrogen and C1-C4-alkyl,orR9 and R10 together with the nitrogen atom to which they are attached form a piperidinyl ring,
where the piperidinyl ring may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of C1-C4-alkyl,R2 is selected from the group consisting of hydrogen and halogen,R3 is selected from the group consisting of hydrogen, halogen, hydroxy and C1-C4-alkoxy,R4 is selected from the group consisting of C1-C3-alkyl, C1-C3-alkoxycarbonyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C3-alkoxy, C3-C6-cycloalkoxy, trifluoromethoxy-C1-C4-alkoxy, 5- or 6-membered heteroaryl and —OCONR11R12, where alkyl may be substituted by a substituent selected from the group consisting of C1-C4-alkoxy, C3-C6-cycloalkoxy, trifluoromethoxy and phenoxy,
in which this phenoxy for its part may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of halogen,andwhere heteroaryl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of C1-C4-alkyl and C3-C6-cycloalkyl,
in which this alkyl for its part may be substituted by a substituent selected from the group consisting of C1-C3-alkoxy and C3-C6-cycloalkyl,R11 represents C1-C4-alkyl or C3-C6-cycloalkyl,R12 is selected from the group consisting of hydrogen and C1-C4-alkyl,orR11 and R12 together with the nitrogen atom to which they are attached form a pyrrolidinyl ring, R5 represents hydrogen or C1-C4-alkyl, or one of the salts thereof, solvates thereof or solvates of the salts thereof.