Aryl-substituted heterocycles, process for their preparation and their use as medicaments

A compound of the formula I,

• wherein:
• R1, R2 independently of one another H, (C1-C8)-alkyl, —(CR13R14)o-R12, (C1-C4)-alkoxy-(C1-C4)-alkyl, (C3-C8)-alkenyl, (C3-C8)-alkynyl, CO—(C1-C8)-alkyl, —CO—(CH2)o—R12, CO(C(R15)(R16))qN(R17)(R18), CO(C(R19)(R20))sO(R21);
• or R1 and R2 form together with the nitrogen atom to which they are bonded a 4 to 10-membered mono-, bi- or spirocyclic ring which, apart from the nitrogen atom, may include 0 to 4 additional heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the heterocyclic ring system may additionally be substituted by F, Cl, Br, CF3, NO2, CN, (C1-C6)-alkyl, O—(C1-C8)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, hydroxy-(C1-C4)-alkyl, (C0-C8)-alkylene-aryl, oxo, CO(R22), CON(R23)(R24), hydroxy, COO(R25), N(R26)CO(C1-C6)-alkyl, N(R27)(R28) or SO2CH3;
• o 0, 1, 2, 3, 4, 5, 6;
• q, s independently of one another 0, 1, 2, 3, 4;
• R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28 independently of one another H, (C1-C6)-alkyl;
• R17 and R18, R23 and R24, R27 and R28 independently of one another optionally together with the nitrogen atom to which they are bonded a 5-6 membered ring which, apart from the nitrogen atom, may also include 0-1 further heteroatoms from the group of NH, N—(C1-C6)-alkyl, oxygen and sulfur;
• R12 OH, O—(C1-C6)-alkyl, CN, COO(R29), CON(R30)(R31), N(R32)(R33), 3-12 membered mono-, bi- or spirocyclic ring which may comprise one or more heteroatoms from the group of N, O and S, and the 3-12 membered ring may comprise further substituents such as F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, oxo, O—(C1-C6)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C3-C8)-cycloalkyl, (C2-C6)-alkynyl, O—(C0-C8)-alkylene-aryl, (C0-C8)-alkylene-aryl, N(R34)(R35), CO(C1-C6)-alkyl, COO(R36) and S(O)u(R37);
• u 0, 1,2;
• R34, R35 independently of one another H, (C1-C8)-alkyl;
• R34 and R35
• optionally together with the nitrogen atom to which they are bonded a 5-6 membered ring which, apart from the nitrogen atom, may also include 0-1 further heteroatoms from the group of NH, N—(C1-C6)-alkyl, oxygen and sulfur, and optionally be substituted by 1-2 oxo groups;
• R36, R37 H, (C1-C8)-alkyl;
• R13, R14 independently of one another H, (C1-C8)-alkyl, hydroxy-(C1-C4)-alkyl, OH, (C1-C4)-alkoxy-(C1-C4)-alkyl;
• R29, R30, R31
• independently of one another H, (C1-C8)-alkyl, (C2-C6)-alkenyl, (C0-C8)-alkylene-aryl;
• R32, R33 independently of one another H, (C1-C6)-alkyl
• or
• R32 and R33
• optionally together with the nitrogen atom to which they are bonded a 5-6 membered ring which, apart from the nitrogen atom, may also include 0-1 further heteroatoms from the group of NH, N—(C1-C6)-alkyl, oxygen and sulfur and optionally be substituted by 1-2 oxo groups;
• R3 H, (C1-C6)-alkyl;
• R4, R5 independently of one another H, (C1-C6)-alkyl, OH, O—(C1-C6)-alkyl, O—CO(C1-C6)-alkyl, S—(C1-C6)-alkyl;
• R6, R7, R8, R9
• independently of one another H, (C1-C8)-alkyl,
• or
• R6 and R7, R8 and R9
• independently of one another optionally oxo;
• n, m are 1;
• A, B, D, G independently of one another C(R38);
• R38 H, F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, O—(C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C3-C8)-cycloalkyl, O—(C3-C8)-cycloalkyl, (C3-C8)-cycloalkenyl, O—(C3-C8)-cycloalkenyl, (C2-C6)-alkynyl, (C0-C8)-alkylene-aryl, O—(C0-C8)-alkylene-aryl, S-aryl, N(R39)(R40), SO2—CH3, COOH, COO—(C1-C6)-alkyl, CON(R41)(R42), N(R43)CO(R44), N(R45)SO2(R46), CO(R47), —(CR48R49)x-O(R50);
• R39, R40, R41, R42, R43, R45
• independently of one another H, (C1-C8)-alkyl;
• or
• R39 and R40, R41 and R42
• independently of one another optionally together with the nitrogen atom to which they are bonded a 5-6 membered ring which, apart from the nitrogen atom, may also include 0-1 further heteroatoms from the group of NH, N—(C1-C6)-alkyl, oxygen and sulfur;
• R44, R46, R47
• independently of one another H, (C1-C8)-alkyl, aryl;
• R48, R49 independently of one another H, (C1-C8)-alkyl;
• R50 H, (C1-C6)-alkyl;
• x 1, 2, 3, 4;
• Het represents 1,2,4-oxadiazolyl;
• X a bond, a group of the formula —(CR51R52)y- in which one or more —(CR51R52)- groups may be replaced by Y, C═C, C≡C;
• Y O, S, N(R53), CO, SO, SO2;
• R51, R52 independently of one another H, (C1-C4)-alkyl, where R51 and R52 in the y groups may in each case have the same or different meanings;
• y 1, 2, 3, 4, 5, 6;
• R53 H, (C1-C8)-alkyl;
• E 3-14 membered bivalent carbo- or heterocyclic ring structure having 0-4 heteroatoms from the group of N, O and S, which may optionally have substituents from the group of H, F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, oxo, O—(C1-C6)-alkyl, O—(C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C3-C8)-cycloalkyl, O—(C3-C8)-cycloalkyl, (C2-C6)-alkynyl, (C0-C8)-alkylene-aryl, O—(C0-C8)-alkylene-aryl, S-aryl, N(R54)(R55), SO2-CH3, COOH, COO—(C1-C6)-alkyl, CON(R56)(R57), N(R58)CO(R59), N(R60)SO2(R61), CO(R62) and be mono- or bicyclic;
• R54, R55, R56, R57, R58, R60
• independently of one another H, (C1-C8)-alkyl;
• R54 and R55, R56 and R57
• independently of one another optionally together with the nitrogen atom to which they are bonded a 5-6 membered ring which, apart from the nitrogen atom, may also include 0-1 further heteroatoms from the group of NH, N—(C1-C6)-alkyl, oxygen and sulfur;
• R59, R61, R62
• independently of one another H, (C1-C8)-alkyl, aryl;
• K a bond, a group of the formula —(CR63R64)z- in which one or more —(CR63R64)- groups may be replaced by Z, C≡C, C═C;
• Z O, S, N(R65), CO, SO, SO2;
• R63, R64 independently of one another H, (C1-C8)-alkyl, hydroxy, (C1-C6)-alkoxy, where R63 and R64 in the z groups may in each case have the same or different meanings;
• z 1, 2, 3, 4, 5, 6;
• R65 H, (C1-C8)-alkyl;
• R11 H, (C1-C8)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, (C3-C8)-alkenyl, (C3-C8)-alkynyl, a 3 to 10-membered mono-, bi- or spirocyclic ring which may include 0 to 4 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system may additionally be substituted by F, Cl, Br, CF3, NO2, CN, (C1-C1)-alkyl, O—(C1-C8)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, (C0-C8)-alkylene-aryl, oxo, CO(R66), CON(R67)(R68), hydroxy, hydroxy-(C1-C4)-alkyl, COO(R69), N(R70)CO(C1-C6)-alkyl, N(R71)(R72) or SO2CH3;
• R66, R67, R68, R69, R70, R71, R72
• independently of one another H, (C1-C8)-alkyl;
• or
• R67 and R68, R71 and R72
• independently of one another optionally together with the nitrogen atom to which they are bonded a 5-6 membered ring which, apart from the nitrogen atom, may also include 0-1 further heteroatoms from the group of NH, N—(C1-C6)-alkyl, oxygen and sulfur;
• or
• N-oxides thereof and physiologically tolerated salts thereof.