Substituted 2-(chroman-6-yloxy)-thiazoles and their use as pharmaceuticals

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
• Ar is selected from the series consisting of phenyl and a 5-membered or 6-membered monocyclic aromatic heterocycle, which are all unsubstituted or substituted by one or more identical or different substituents R1, wherein the heterocycle comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur and is bonded via a ring carbon atom;
• R1 is selected from the series consisting of halogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl-, phenyl, Het1, HO—, (C1-C6)-alkyl-O—, (C3-C7)-cycloalkyl-O—, (C3-C7)-cycloalkyl-(C1-C4)-alkyl-O—, phenyl-O—, Het1-O— and (C1-C6)-alkyl-S(O)n—, and two groups R1 bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 7-membered mono-unsaturated ring which comprises 0, 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;
• R2 is selected from the series consisting of R5-N(R6)-C(O)—, R5-N(R6)-CH2—, R7-C(O)—NH—CH2— and R7-S(O)2—NH—CH2—;
• R3 is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and (C1-C4)-alkyl-O—;
• R4 is hydrogen or one or more identical or different substituents selected from the series consisting of halogen, (C1-C4)-alkyl and (C1-C4)-alkyl-O—;
• R5 and R6 are independently of one another selected from the series consisting of hydrogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, (C6-C10)-bicycloalkyl, phenyl, Het1 and Het2, wherein (C1-C6)-alkyl is unsubstituted or substituted by one or more identical or different substituents R10, and (C3-C7)-cycloalkyl, (C6-C10)-bicycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R11,
• or the groups R5 and R6, together with the nitrogen atom carrying them, form a 4-membered to 10-membered, monocyclic or bicyclic, saturated or partially unsaturated heterocycle which, in addition to the nitrogen atom carrying R5 and R6, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R12;
• R7 is selected from the series consisting of (C1-C6)-alkyl, (C3-C7)-cycloalkyl, phenyl, Het2 and Het3, wherein (C1-C6)-alkyl, (C3-C7)-cycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R10, and phenyl and Het3 all are unsubstituted or substituted by one or more identical or different substituents R13;
• R10 is selected from the series consisting of R14, fluorine, HO—, oxo, (C1-C6)-alkyl-O—, R15-C(O)—O—, R15-NH—C(O)—O—, HO—S(O)2—O—, (HO)2P(O)—O—, (HO)2P(O)—O—CH2—O—C(O)—O—, (C1-C6)-alkyl-S(O)n—, R16-N(R17)-, R18-C(O)—N(R17)-, R16-N(R17)-C(O)—, R19-O—C(O)— and R16-N(R17)-S(O)2—;
• R11 and R12 are independently of one another selected from the series consisting of (C1-C4)-alkyl, HO—(C1-C4)-alkyl-, R16-N(R17)-(C1-C4)-alkyl-, R19-O—C(O)—(C1-C4)-alkyl-, R14, fluorine, HO—, oxo, (C1-C6)-alkyl-O—, R15-C(O)—O—, R15-NH—C(O)—O—, HO—S(O)2-O—, (HO)2P(O)—O—, (HO)2P(O)—O—CH2—O—C(O)—O—, (C1-C6)-alkyl-S(O)n—, R16-N(R17)-, R18-C(O)—N(R17)-, R16-N(R17)-C(O)—, R19-O—C(O)— and R16-N(R17)-S(O)2—;
• R13 is selected from the series consisting of halogen, (C1-C4)-alkyl, HO—, (C1-C4)-alkyl-O— and R16-N(R17)-, and two substituents R13 bonded to adjacent ring carbon atoms in R7, together with the carbon atoms carrying them, can form a 5-membered to 7-membered mono-unsaturated ring which comprises 0, 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;
• R14 is a 3-membered to 10-membered, monocyclic or bicyclic ring which is saturated, partially unsaturated or aromatic and comprises 0, 1, 2, 3 or 4 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R20;
• R15 and R18 are independently of one another selected from the series consisting of (C1-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl-, phenyl-(C1-C4)-alkyl- and Het1-(C1-C4)-alkyl-;
• R16 and R17 are independently of one another selected from the series consisting of hydrogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl-, phenyl-(C1-C4)-alkyl- and Het1-(C1-C4)-alkyl-,
• or the groups R16 and R17, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic saturated heterocycle which, in addition to the nitrogen atom carrying R16 and R17, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;
• R19 is selected from the series consisting of hydrogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl-, phenyl-(C1-C4)-alkyl- and Het1-(C1-C4)-alkyl-;
• R20 is selected from the series consisting of halogen, (C1-C4)-alkyl, HO—(C1-C4)-alkyl-, (C3-C7)-cycloalkyl, HO—, oxo, (C1-C6)-alkyl-O—, R15-C(O)—O—, R15-NH—C(O)—O—, HO—S(O)2—O—, (HO)2P(O)—O—, (HO)2P(O)—O—CH2—O—C(O)—O—, (C1-C6)-alkyl-S(O)n—, R16-N(R17)-, R18-C(O)—N(R17)-, R18-O—C(O)—N(R17)-, NC—, R18-C(O)—, R16-N(R17)-C(O)—, R19-O—C(O)— and R16-N(R17)-S(O)2—;
• Het1 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, which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (C1-C4)-alkyl and (C1-C4)-alkyl-O—;
• Het2 is a 4-membered to 10-membered monocyclic or bicyclic, saturated or partially unsaturated heterocycle comprising 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur;
• Het3 is a 5-membered to 10-membered monocyclic or bicyclic aromatic heterocycle comprising 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur;
• n is selected from the series consisting of 0, 1 and 2, wherein all numbers n are independent of one another;
• wherein all phenyl groups, unless specified otherwise, are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (C1-C4)-alkyl and —O—(C1-C4)-alkyl;
• wherein all cycloalkyl and bicycloalkyl groups, independently of any other substituents which can be present on a cycloalkyl or bicycloalkyl group, can be substituted by one or more identical substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;
• wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.