Aryl-substituted heterocycles, process for their preparation and their use as medicaments
The invention relates to substituted aryl-substituted heterocycles and to the physiologically tolerated salts and physiologically functional derivatives thereof, to process for their preparation and to their use as medicaments. Compounds of the formula I in which the radicals have the stated meanings, the N-oxides thereof, and the physiologically tolerated salts thereof, and process for the preparation thereof are described. The compounds bring about for example a weight reduction in mammals and are suitable for example for the prevention and treatment of obesity and diabetes.
1. A compound of the formula I,
wherein:
R1, R2 independently of one another H, (C 1 -C 8 )-alkyl, —(CR13R14) o -R12, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, (C 3 -C 8 )-alkenyl, (C 3 -C 8 )-alkynyl, CO—(C 1 -C 8 )-alkyl, —CO—(CH 2 ) o —R12, CO(C(R15)(R16)) q N(R17)(R18), CO(C(R19)(R20)) s O(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, CF 3 , NO 2 , CN, (C 1 -C 6 )-alkyl, O—(C 1 -C 8 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, hydroxy-(C 1 -C 4 )-alkyl, (C 0 -C 8 )-alkylene-aryl, oxo, CO(R22), CON(R23)(R24), hydroxy, COO(R25), N(R26)CO(C 1 -C 6 )-alkyl, N(R27)(R28) or SO 2 CH 3 ;
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, (C 1 -C 6 )-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—(C 1 -C 6 )-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, CF 3 , NO 2 , CN, OCF 3 , oxo, O—(C 1 -C 6 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, S—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 3 -C 8 )-cycloalkyl, (C 2 -C 6 )-alkynyl, O—(C 0 -C 8 )-alkylene-aryl, (C 0 -C 8 )-alkylene-aryl, N(R34)(R35), CO(C 1 -C 6 )-alkyl, COO(R36) and S(O) u (R37);
u 0, 1,2;
R34, R35 independently of one another H, (C 1 -C 8 )-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—(C 1 -C 6 )-alkyl, oxygen and sulfur, and optionally be substituted by 1-2 oxo groups;
R36, R37 H, (C 1 -C 8 )-alkyl;
R13, R14 independently of one another H, (C 1 -C 8 )-alkyl, hydroxy-(C 1 -C 4 )-alkyl, OH, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl;
R29, R30, R31
independently of one another H, (C 1 -C 8 )-alkyl, (C 2 -C 6 )-alkenyl, (C 0 -C 8 )-alkylene-aryl;
R32, R33 independently of one another H, (C 1 -C 6 )-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—(C 1 -C 6 )-alkyl, oxygen and sulfur and optionally be substituted by 1-2 oxo groups;
R3 H, (C 1 -C 6 )-alkyl;
R4, R5 independently of one another H, (C 1 -C 6 )-alkyl, OH, O—(C 1 -C 6 )-alkyl, O—CO(C 1 -C 6 )-alkyl, S—(C 1 -C 6 )-alkyl;
R6, R7, R8, R9
independently of one another H, (C 1 -C 8 )-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, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 -C 6 )-alkyl, O—(C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, S—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 3 -C 8 )-cycloalkyl, O—(C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkenyl, O—(C 3 -C 8 )-cycloalkenyl, (C 2 -C 6 )-alkynyl, (C 0 -C 8 )-alkylene-aryl, O—(C 0 -C 8 )-alkylene-aryl, S-aryl, N(R39)(R40), SO 2 —CH 3 , COOH, COO—(C 1 -C 6 )-alkyl, CON(R41)(R42), N(R43)CO(R44), N(R45)SO 2 (R46), CO(R47), —(CR48R49) x -O(R50);
R39, R40, R41, R42, R43, R45
independently of one another H, (C 1 -C 8 )-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—(C 1 -C 6 )-alkyl, oxygen and sulfur;
R44, R46, R47
independently of one another H, (C 1 -C 8 )-alkyl, aryl;
R48, R49 independently of one another H, (C 1 -C 8 )-alkyl;
R50 H, (C 1 -C 6 )-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, SO 2 ;
R51, R52 independently of one another H, (C 1 -C 4 )-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, (C 1 -C 8 )-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, CF 3 , NO 2 , CN, OCF 3 , oxo, O—(C 1 -C 6 )-alkyl, O—(C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, S—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 3 -C 8 )-cycloalkyl, O—(C 3 -C 8 )-cycloalkyl, (C 2 -C 6 )-alkynyl, (C 0 -C 8 )-alkylene-aryl, O—(C 0 -C 8 )-alkylene-aryl, S-aryl, N(R54)(R55), SO 2 -CH 3 , COOH, COO—(C 1 -C 6 )-alkyl, CON(R56)(R57), N(R58)CO(R59), N(R60)SO 2 (R61), CO(R62) and be mono- or bicyclic;
R54, R55, R56, R57, R58, R60
independently of one another H, (C 1 -C 8 )-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—(C 1 -C 6 )-alkyl, oxygen and sulfur;
R59, R61, R62
independently of one another H, (C 1 -C 8 )-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, SO 2 ;
R63, R64 independently of one another H, (C 1 -C 8 )-alkyl, hydroxy, (C 1 -C 6 )-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, (C 1 -C 8 )-alkyl;
R11 H, (C 1 -C 8 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, (C 3 -C 8 )-alkenyl, (C 3 -C 8 )-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, CF 3 , NO 2 , CN, (C 1 -C 1 )-alkyl, O—(C 1 -C 8 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, (C 0 -C 8 )-alkylene-aryl, oxo, CO(R66), CON(R67)(R68), hydroxy, hydroxy-(C 1 -C 4 )-alkyl, COO(R69), N(R70)CO(C 1 -C 6 )-alkyl, N(R71)(R72) or SO 2 CH 3 ;
R66, R67, R68, R69, R70, R71, R72
independently of one another H, (C 1 -C 8 )-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—(C 1 -C 6 )-alkyl, oxygen and sulfur; or
N-oxides thereof and physiologically tolerated salts thereof.
2. A compound of the formula I as claimed in claim 1 ,
wherein:
R1, R2 independently of one another H, (C 1 -C 8 )-alkyl, —(CR13R14) o -R12, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, (C 3 -C 8 )-alkenyl, (C 3 -C 8 )-alkynyl, CO—(C 1 -C 8 )-alkyl, —CO—(CH 2 ) o —R12, CO(C(R15)(R16)) q N(R17)(R18), CO(C(R19)(R20)) s O(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, CF 3 , NO 2 , CN, (C 1 -C 6 )-alkyl, O—(C 1 -C 8 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, hydroxy-(C 1 -C 4 )-alkyl, (C 0 -C 8 )-alkylene-aryl, oxo, CO(R22), CON(R23)(R24), hydroxy, COO(R25), N(R26)CO(C 1 -C 6 )-alkyl or N(R27)(R28);
R12 OH, O—(C 1 -C 6 )-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, CF 3 , NO 2 , CN, OCF 3 , oxo, O—(C 1 -C 6 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, S-(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 3 -C 8 )-cycloalkyl, (C 2 -C 6 )-alkynyl, O—(C 0 -C 8 )-alkylene-aryl, (C 0 -C 8 )-alkylene-aryl, N(R34)(R35), CO(C 1 -C 6 )-alkyl and COO(R36);
and
R6, R7, R8, R9
independently of one another H, (C 1 -C 8 )-alkyl;
where the further radicals and groups in the compound of the formula I have the meanings stated in claim 1 .
3. A compound of the formula I as claimed in claim 1 , wherein:
R1, R2 independently of one another H, (C 1 -C 8 )-alkyl, —(CR13R14) o -R12, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, (C 3 -C 8 )-alkenyl, CO—(C 1 -C 8 )-alkyl, —CO—(CH 2 ) o —R12, CO(C(R15)(R16)) q N(R17)(R18), CO(C(R19)(R20)) s O(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 2 additional heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the heterocyclic ring system may additionally be substituted by F, Cl, CF 3 , (C 1 -C 6 )-alkyl, O—(C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, hydroxy-(C 1 -C 4 )-alkyl, (C 0 -C 2 )-alkylene-aryl, oxo, CO(R22), CON(R23)(R24), hydroxy, COO(R25), N(R26)CO(C 1 -C 6 )-alkyl, N(R27)(R28) or SO 2 CH 3 ;
o 0, 1, 2, 3, 4, 5, 6;
q 1, 2, 3;
s 0, 1, 2, 3, 4;
R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28
independently of one another H, (C 1 -C 6 )-alkyl;
or
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—(C 1 -C 6 )-alkyl, oxygen and sulfur;
R12 OH, O—(C 1 -C 6 )-alkyl, CN, COO(R29), CON(R30)(R31), 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, OH, CF 3 , CN, oxo, O—(C 1 -C 6 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, (C 1 -C 6 )-alkyl, O—(C 0 -C 8 )-alkylene-aryl, (C 0 -C 8 )-alkylene-aryl, N(R34)(R35), CO(C 1 -C 6 )-alkyl, COO(R36), S(O) u (R37);
u 0, 1, 2;
R34, R35
independently of one another H, (C 1 -C 8 )-alkyl;
or
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—(C 1 -C 6 )-alkyl, oxygen and sulfur, and optionally be substituted by 1-2 oxo groups;
R36, R37 H, (C 1 -C 8 )-alkyl;
R13, R14 independently of one another H, (C 1 -C 8 )-alkyl, hydroxy-(C 1 -C 4 )-alkyl, OH, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl;
R29, R30, R31
independently of one another H, (C 1 -C 8 )-alkyl;
R3 H, (C 1 -C 6 )-alkyl;
R4, R5 independently of one another H, (C 1 -C 6 )-alkyl, OH, O—(C 1 -C 6 )-alkyl, O—CO(C 1 -C 6 )-alkyl, S—(C 1 -C 6 )-alkyl;
R6, R7, R8, R9
H;
or
R6 and R7, R8 and R9
independently of one another optionally oxo;
n 1
m 1;
A, B, D, G
independently of one another C(R38);
or
the groups A and B or D and G are in each case C(R38) and together form an ortho-phenylene unit so that the overall result is a 1,4-bisubstituted naphthalene system;
R38 H, F, Cl, Br, CF 3 , CN, O—(C 1 -C 6 )-alkyl, O—(C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, S—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 0 -C 8 )-alkylene-aryl, O—(C 0 -C 8 )-alkylene-aryl, N(R39)(R40), SO 2 -CH 3 , CON(R41)(R42), N(R43)CO(R44), CO(R47), —(CR48R49) x -O(R50);
R39, R40, R41, R42, R43
independently of one another H, (C 1 -C 8 )-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-(C 1 -C 6 )-alkyl, oxygen and sulfur;
R44, R47
independently of one another H, (C 1 -C 8 )-alkyl, aryl;
R48, R49 H;
R50 H, (C 1 -C 6 )-alkyl;
x 1, 2;
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;
R51, R52 independently of one another H, (C 1 -C 4 )-alkyl, where R51 and R52 in the y groups may in each case have the same or different meanings;
Y O, S, N(R53), CO;
R53 H, (C 1 -C 8 )-alkyl;
E 3-8 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, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 -C 6 )-alkyl, O—(C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, S—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, O—(C 3 -C 8 )-cycloalkyl, (C 2 -C 6 )-alkynyl, (C 0 -C 8 )-alkylene-aryl, O—(C 0 -C 8 )-alkylene-aryl, S-aryl, N(R54)(R55), SO 2 -CH 3 , N(R58)CO(R59), N(R60)SO 2 (R61), CO(R62) and be mono- or bicyclic;
R54, R55, R58, R60
independently of one another H, (C 1 -C 8 )-alkyl;
R59, R61, R62
independently of one another H, (C 1 -C 8 )-alkyl, aryl;
K O, a bond, CH 2 O, OCH 2 , S, SO, SO 2 , N(R80), N(R81)CO, CON(R82), (C(R83)(R84)) v , CO, C═C, C≡C, SCH 2 , SO 2 CH 2 ;
v 1, 2, 3, 4;
R80, R81, R82, R83, R84
independently of one another H, (C 1 -C 8 )-alkyl;
R11 H, (C 1 -C 8 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, (C 3 -C 8 )-alkenyl, (C 3 -C 8 )-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, CF 3 , CN, (C 1 -C 6 )-alkyl, O—(C 1 -C 8 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, hydroxy-(C 1 -C 4 )-alkyl, (C 0 -C 8 )-alkylene-aryl, oxo, CO(R66), CON(R67)(R68), hydroxy, COO(R69), N(R70)CO(C 1 -C 6 )-alkyl, N(R71)(R72) or SO 2 CH 3 ;
R66, R67, R68, R69, R70, R71, R72
independently of one another H, (C 1 -C 8 )-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—(C 1 -C 6 )-alkyl, oxygen and sulfur; or
N-oxides thereof and physiologically tolerated salts thereof.
4. A compound of the formula I as claimed in claim 1 , wherein:
R1, R2 independently of one another H, (C 1 -C 8 )-alkyl, —(CR13R14) o -R12, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, CO—(C 1 -C 8 )-alkyl, —CO—(CH 2 ) o —R12, CO(C(R15)(R16)) q N(R17)(R18), CO(C(R19)(R20)) s O(R21); or R1 and R2 form together with the nitrogen atom to which they are bonded a 4 to 10-membered mono- or bicyclic ring which, apart from the nitrogen atom, may include 0 to 2 additional heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the heterocyclic ring system may additionally be substituted by F, Cl, CF 3 , (C 1 -C 6 )-alkyl, O—(C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, (C 0 -C 2 )-alkylene-aryl, oxo, CO(R22), hydroxy, N(R27)(R28) or SO 2 CH 3 ;
o 0, 1, 2, 3, 4;
q 1 or 2;
s 0, 1, 2, 3;
R15, R16, R17, R18, R19, R20, R21, R22, R27, R28
independently of one another H, (C 1 -C 6 )-alkyl;
or
R17 and R18, R27 and R28
independently of one another optionally together with the nitrogen atom to which they are bonded a 5-6 membered ring selected from pyrrolidine, piperidine, N-methylpiperazine and morpholine;
R12 OH, O—(C 1 -C 6 )-alkyl, CN, 3-10 membered mono- or bicyclic ring which may comprise 1-3 heteroatoms from the group of N, O and S, and the 3-10 membered ring may comprise further substituents such as F, Cl, Br, OH, CF 3 , CN, oxo, O—(C 1 -C 6 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, (C 1 -C 6 )-alkyl, (C 0 -C 2 )-alkylene-aryl, N(R34)(R35), CO(C 1 -C 6 )-alkyl;
u 0 or 2;
R34, R35
independently of one another H, (C 1 -C 8 )-alkyl;
or
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—(C 1 -C 6 )-alkyl, oxygen and sulfur, and optionally be substituted by 1-2 oxo groups;
R36, R37 H, (C 1 -C 8 )-alkyl;
R13, R14 independently of one another H, (C 1 -C 8 )-alkyl, hydroxy-(C 1 -C 4 )-alkyl, OH, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl;
R3 H;
R4, R5 independently of one another H, (C 1 -C 6 )-alkyl, OH, O—(C 1 -C 6 )-alkyl, O—CO(C 1 -C 6 )-alkyl;
R6, R7, R8, R9 H;
n 1
m 1;
A, B, D, G C(R38);
R38 H, F, Cl, Br, CF 3 , CN, O—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, SO 2 -CH 3 , CON(R41)(R42), N(R43)CO(R44), CO(R47),
—(CR48R49) x -O(R50);
R41, R42, R43 independently of one another H, (C 1 -C 8 )-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—(C 1 -C 6 )-alkyl, oxygen and sulfur;
R47 H, (C 1 -C 8 )-alkyl;
R48, R49 H;
R50 H, (C 1 -C 6 )-alkyl;
x 1;
Het represents 1,2,4-oxadiazolyl;
X a bond, CH 2 —CH 2 , CH 2 Y, YCH 2 , (R75)YCH 2 , CH 2 —NCO(R75), CH 2 CON(R75);
C(R76)(R77), C(R78)(R79)O, N(R75), C═C, C≡C;
Y O, S, N(R53);
R53 H, (C 1 -C 8 )-alkyl;
R75, R76, R77, R78, R79
independently of one another H, (C 1 -C 8 )-alkyl;
E 5-7 membered bivalent carbo- or heterocyclic ring structure having 0-3 heteroatoms from the group of N, O and S, which may optionally have substituents from the group of H, F, Cl, Br, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 -C 6 )-alkyl, S—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, O—(C 0 -C 8 )-alkylene-aryl, S-aryl, N(R54)(R55), SO 2 —CH 3 , N(R58)CO(R59), CO(R62) and be mono-or bicyclic;
R54, R55, R58
independently of one another H, (C 1 -C 8 )-alkyl;
R59, R62 independently of one another H, (C 1 -C 8 )-alkyl;
K O, a bond, CH 2 O, OCH 2 , N(R80), N(R81)CO, CON(R82), (C(R83)(R84)) v , CO, C≡C, SCH 2 ;
v 1, 2, 3;
R80, R81, R83, R84
independently of one another H, (C 1 -C 8 )-alkyl;
R11 (C 1 -C 8 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, a 3 to 10-membered mono-, bi- or spirocyclic ring which may include 0 to 3 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system may additionally be substituted by F, Cl, Br, CF 3 , CN, (C 1 -C 6 )-alkyl, O—(C 1 -C 8 )-alkyl, (C 0 -C 2 )-alkylene-aryl, oxo, CO(R66), CON(R67)(R68), hydroxy, N(R70)CO(C 1 -C 6 )-alkyl, N(R71)(R72) or SO 2 CH 3 ;
R66, R67, R68, R70, R71, R72
independently of one another H, (C 1 -C 8 )-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—(C 1 -C 6 )-alkyl, oxygen and sulfur; or N-oxides thereof and physiologically tolerated salts thereof.
5. A compound of the formula I as claimed in claim 1 , in which radicals R1, R2, R11, R38 and the groups X, E and K have the following meanings:
R1, R2 independently of one another H, (C 1 -C 8 )-alkyl, —(CR13R14) o -R12, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, 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 2 additional heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the heterocyclic ring system may additionally be substituted by (C 1 -C 6 )-alkyl, O—(C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, hydroxy-(C 1 -C 4 )-alkyl, (C 0 -C 2 )-alkylene-aryl, oxo, CO(R22), CON(R23)(R24), hydroxy, N(R27)(R28) or SO 2 CH 3 ;
o 0, 1, 2, 3, 4;
R22, R23, R24, R27, R28
independently of one another H, (C 1 -C 6 )-alkyl;
or
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—(C 1 -C 6 )-alkyl, oxygen and sulfur;
R12 OH, O—(C 1 -C 6 )-alkyl, CN 3-12 membered mono-, bi- or spirocyclic ring which may comprise 1 to 3 heteroatoms from the group of N, O and S, and the 3-12 membered ring may comprise further substituents such as F, OH, CF 3 , CN, oxo, (C 1 -C 6 )-alkyl, (C 0 -C 2 )-alkylene-aryl, N(R34)(R35), COO(R36), CO(C 1 -C 6 )-alkyl;
R34, R35
independently of one another H, (C 1 -C 4 )-alkyl;
R36 H, (C 1 -C 6 )-alkyl, (C 0 -C 2 )-alkylene-aryl;
R13, R14 independently of one another H, (C 1 -C 8 )-alkyl, hydroxy-(C 1 -C 4 )-alkyl, OH, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl;
R38 H, F, Cl, Br, CF 3 , CN, (C 1 -C 6 )-alkyl;
X a bond, CH 2 CH 2 , C(R76)(R77), N(R75), C═C, (R75)YCH 2 , CH 2 —NCO(R75), CH 2 CON(R75);
Y O, S, N(R53), CO
R75, R76, R77
independently of one another H, (C 1 -C 8 )-alkyl;
R53 H, (C 1 -C 8 )-alkyl;
E 5-7 membered bivalent carbo- or heterocyclic ring structure having 0-3 heteroatoms from the group of N, O and S, which may optionally have substituents from the group of H, F, Cl, Br, CF 3 , OH, CN, OCF 3 , O—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, SO 2 -CH 3 , CO(R65);
R65 H, (C 1 -C 8 )-alkyl;
K O, a bond, CH 2 O, CH 2 , OCH 2 , S, SO 2 , N(R80), N(R81)CO, CON(R82), (C(R83)(R84)) v , CO, C≡C, SCH 2 , SO 2 CH 2 ;
v 1, 2, 3;
R80, R81, R82, R83, R84
independently of one another H, (C 1 -C 8 )-alkyl;
R11 (C 1 -C 8 )-alkyl, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, 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, CF 3 , CN, (C 1 -C 6 )-alkyl, O—(C 1 -C 8 )-alkyl, oxo, CO(R66), hydroxy, N(R70)CO(C 1 -C 6 )-alkyl, or SO 2 CH 3 ;
R66, R70
independently of one another H, (C 1 -C 8 )-alkyl;
N-oxides thereof and physiologically tolerated salts thereof.
6. A compound of the formula I as claimed in claim 1 , in which
A, B, D, G are independently of one another C(R38).
7. A compound of the formula I as claimed in claim 1 , in which
n is 1 and
m is 1.
8. A medicament comprising one or more of the compounds as claimed in claim 1 .
9. A medicament comprising one or more of the compounds as claimed in claim 1 and one or more anorectic active ingredients.
10. A compound of the formula I as claimed in claim 1 for use as medicament for the treatment of obesity.
11. A compound of the formula I as claimed in any one of claims 1 to 7 for use as medicament for the treatment of type II diabetes.