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

• US 20050176710A1
• Filed: 01/25/2005
• Published: 08/11/2005
• Est. Priority Date: 01/25/2004
• Status: Active Grant

• Current Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Original Assignee: Aventis Pharma Deutschland GmbH (Sanofi )
• Inventors: Schwink, Lothar, Hessler, Gerhard, Stengelin, Siegfried, Gossel, Matthias, Boehme, Thomas, Stahl, Petra
• Granted Patent: US 7,319,108 B2
• Time in Patent Office: Days
• US Class Current: 514/242
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 31/501 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00

Abstract

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.

Claims

1. A compound of the formula 1,

2. A compound of the formula I as claimed in claim 1,

in which the meanings are

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 or N(R27)(R28);

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 and COO(R36); and

R6, R7, R8, R9 independently of one another H, (C₁-C₈)-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,

in which the meanings are

R1, R2 independently of one another H, (C₁-C₈)-alkyl, —

(CR13R14)_o—

R12, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, (C₃-C₈)-alkenyl, 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 2 additional heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the heterocyclic ring system may additionally be substituted by F, Cl, CF₃, (C₁-C₆)-alkyl, O-(C₁-C₄)-alkyl, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, hydroxy-(C₁-C₄)-alkyl, (C₀-C₂)-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 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, (C₁-C₆)-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-(C₁-C₆)-alkyl, oxygen and sulfur;

R12 OH, O-(C₁-C₆)-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, CF₃, CN, oxo, O-(C₁-C₆)-alkyl, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, (C₁-C₆)-alkyl, O-(C₀-C₈)-alkylene-aryl, (C₀-C₈)-alkylene-aryl, N(R34)(R35), CO(C₁-C₆)-alkyl, COO(R36), S(O)_u(R37);

u 0, 1, 2;

R34, R35 independently of one another H, (C₁-C₈)-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-(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;

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 H;

or

R6 and R7, R8 and R9 independently of one another optionally oxo;

n 1

m 1 or 2;

A, B, D, G independently of one another N, 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, CF₃, CN, O-(C₁-C₆)-alkyl, O-(C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, S-(C₁-C₆)-alkyl, (C₁-C₆)-alkyl, (C₀-C₈)-alkylene-aryl, O-(C₀-C₈)-alkylene-aryl, N(R39)(R40), SO₂—

CH₃, CON(R41)(R42), N(R43)CO(R44), CO(R47), —

(CR48R49)_x—

O(R50);

R39, R40, R41, R42, R43 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, R47 independently of one another H, (C₁-C₈)-alkyl, aryl;

R48, R49 H;

R50 H, (C₁-C₆)-alkyl;

x 1, 2;

Het five-membered aromatic heterocycle, preferably

in which

A′

is O, S, NR73,

X′

, Y′ and

Z′

are independently of one another CR74 or N, and

R73, R74 are independently of one another H, (C₁-C₈)-alkyl;

X a bond, a group of the formula —

(CR51R52)_y—

, in which one or more —

(CR51R52)- groups may be replaced by Y to result in a chemically reasonable radical, C═

C, C≡

C;

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 O, S, N(R53), CO;

R53 H, (C₁-C₈)-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, 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, O-(C₃-C₈)-cycloalkyl, (C₂-C₆)-alkynyl, (C₀-C₈)-alkylene-aryl, O-(C₀-C₈)-alkylene-aryl, S-aryl, N(R54)(R55), SO₂—

CH₃, N(R58)CO(R59), N(R60)SO₂(R61), CO(R62) and be mono- or bicyclic;

R54, R55, R58, R60 independently of one another H, (C₁-C₈)-alkyl;

R59, R61, R62 independently of one another H, (C₁-C₈)-alkyl, aryl;

K O, a bond, CH₂O, OCH₂, S, SO, SO₂, N(R80), N(R81)CO, CON(R82), (C(R83)(R84))_v, CO, C═

C, C≡

C, SCH₂, SO₂CH₂;

v 1, 2, 3, 4;

R80, R81, R82, R83, R84 independently of one another 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, CN, (C₁-C₆)-alkyl, O-(C₁-C₈)-alkyl, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, hydroxy-(C₁-C₄)-alkyl, (C₀-C₈)-alkylene-aryl, oxo, CO(R66), CON(R67)(R68), hydroxy, 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

the N-oxides thereof and the physiologically tolerated salts thereof.

4. A compound of the formula I as claimed in claim 1 or 3,

in which the meanings are:

R1, R2 independently of one another H, (C₁-C₈)-alkyl, —

(CR13R14)_o—

R12, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, CO-(C₁-C₈)-alkyl, —

CO—

(CH₂)_o—

R12, CO(C(R15)(R16))_qN(R17)(R18), CO(C(R19)(R20))_oO(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, CF₃, (C₁-C₆)-alkyl, O-(C₁-C₄)-alkyl, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, (C₀-C₂)-alkylene-aryl, oxo, CO(R22), hydroxy, N(R27)(R28) or SO₂CH₃;

preferably independently of one another H, (C₁-C₈)-alkyl, —

(CR13R14)_o—

R12, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, CO-(C₁-C₈)-alkyl, —

CO—

(CH₂)_o—

R12, CO(C(R15)(R11))_qN(R17)(R18), 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 and nitrogen, where the heterocyclic ring system may additionally be substituted by F, (C₁-C₆)-alkyl, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, oxo, CO(R22), hydroxy, N(R27)(R28);

o 0, 1, 2, 3, 4;

preferably 0, 1, 2, 3;

q 1 or 2;

s 0, 1, 2, 3;

preferably 0, 1, 2;

R15, R16, R17, R18, R19, R20, R21, R22, R27, R28 independently of one another H, (C₁-C₆)-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-(C₁-C₆)-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, CF₃, CN, oxo, O-(C₁-C₆)-alkyl, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, (C₁-C₆)-alkyl, (C₀-C₂)-alkylene-aryl, N(R34)(R35), CO(C₁-C₆)-alkyl;

preferably OH, O-(C₁-C₆)-alkyl, 3-10 membered mono- or bicyclic ring which may comprise 1-2 heteroatoms from the group of N, O and S, and the 3-10 membered ring may comprise further substituents such as F, OH, oxo, (C₁-C₆)-alkyl, CO(C₁-C₆)-alkyl;

u 0 or 2;

preferably 2;

R34, R35 independently of one another H, (C₁-C₈)-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-(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;

R3 H;

R4, R5 independently of one another H, (C₁-C₆)-alkyl, OH, O-(C₁-C₆)-alkyl, O—

CO(C₁-C₆)-alkyl;

preferably independently of one another H, OH, O-(C₁-C₆)-alkyl, very particularly preferably H;

R6, R7, R8, R9 H;

n 1

m 1;

A, B, D, G C(R38);

R38 H, F, Cl, Br, CF₃, CN, O-(C₁-C₆)-alkyl, (C₁-C₆)-alkyl, SO₂—

CH₃, CON(R41)(R42), N(R43)CO(R44), CO(R47), —

(CR48R49)_x—

O(R50);

particularly preferably H, F, Cl, CF₃, CN, (C₁-C₆)-alkyl, —

(CR48R49)_x—

O(R50);

R41, R42, R43 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;

R47 H, (C₁-C₈)-alkyl;

R48, R49 H;

R50 H, (C₁-C₆)-alkyl;

x 1;

Het heteroaromatic group selected from the group consisting of oxadiazoles, thiadiazoles, thiazoles, oxazoles, triazoles, thiophenes, furans and pyrroles;

Het is very particularly preferably selected from oxadiazoles, thiadiazoles, thiazoles and oxazoles;

X a bond, CH₂—

CH₂, CH₂Y, YCH₂, (R75)YCH₂, CH₂—

NCO(R75), CH₂CON(R75);

C(R76)(R77), C(R78)(R79)O, N(R75), C═

C, C≡

C;

preferably a bond, CH₂—

CH₂, C(R76)(R77), N(R75), CH₂Y, CH₂Y(R75), CH₂—

NCO(R75), CH₂—

CON(R75);

C═

C;

particularly preferably a bond, CH₂—

CH₂, C(R76)(R77), C═

C, (R75)YCH₂, CH₂—

NCO(R75);

Y O, S, N(R53);

R53 H, (C₁-C₈)-alkyl;

R75, R76, R77, R78, R79 independently of one another H, (C₁-C₈)-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, CF₃, NO₂, CN, OCF₃, O-(C₁-C₆)-alkyl, S-(C₁-C₆)-alkyl, (C₁-C₆)-alkyl, (C₂-C₆)-alkenyl, O-(C₀-C₈)-alkylene-aryl, S-aryl, N(R54)(R55), SO₂—

CH₃, N(R58)CO(R59), CO(R62) and be mono- or bicyclic;

preferably 5-7 membered bivalent carbo- or heterocyclic ring structure having 0-2 heteroatoms from the group of N, O and S, which may optionally have substituents from the group of H, F, Cl, Br, OH, CF₃, NO₂, OCF₃, O-(C₁-C₆)-alkyl, (C₁-C₆)-alkyl, (C₂-C₆)-alkenyl, N(R54)(R55), SO₂—

CH₃, CO(R62), and which is particularly preferably monocyclic;

e.g. E is benzene, pyridine, pyrimidine, piperidine, pyrrolidine, cyclopentane, cyclohexane, piperazine, homopiperazine, thiazole, thiophene, furan, pyrrole, pyrazole, 1,2,3,6-tetrahydropyridine, 4,5-dihydroisoxazole, oxazole;

R54, R55, R58 independently of one another H, (C₁-C₈)-alkyl;

R59, R62 independently of one another H, (C₁-C₈)-alkyl;

K O, a bond, CH₂O, OCH₂, N(R80), N(R81)CO, CON(R82), (C(R83)(R84))_v, CO, C≡

C, SCH₂;

preferably 0, a bond, CH₂O, OCH₂, CON(R82), (C(R83)(R84))_v, CO, C≡

C;

v 1, 2, 3;

preferably 1,2;

R80, R81, R83, R84 independently of one another H, (C₁-C₈)-alkyl;

R11 (C₁-C₈)-alkyl, (C₁-C₄)-alkoxy-(C₁-C₄)-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, CF₃, CN, (C₁-C₆)-alkyl, O-(C₁-C₈)-alkyl, (C₀-C₂)-alkylene-aryl, oxo, CO(R66), CON(R67)(R68), hydroxy, N(R70)CO(C₁-C₆)-alkyl, N(R71)(R72) or SO₂CH₃;

preferably (C₁-C₈)-alkyl, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, a 3 to 10-membered mono- or bicyclic ring which may include 0 to 2 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system may additionally be substituted by F, Cl, Br, CF₃, CN, (C₁-C₆)-alkyl, O-(C₁-C₈)-alkyl, oxo, CO(R66), CON(R67)(R68), N(R70)CO(C₁-C₆)-alkyl, or SO₂CH₃;

R66, R67, R68, 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

the N-oxides thereof and the physiologically tolerated salts thereof.

5. A compound of the formula I as claimed in any of claims 1 or 2 to 4,

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, (C₁-C₈)-alkyl, —

(CR13R14)_o—

R12, (C₁-C₄)-alkoxy-(C₁-C₄)-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 (C₁-C₆)-alkyl, O-(C₁-C₄)-alkyl, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, hydroxy-(C₁-C₄)-alkyl, (C₀-C₂)-alkylene-aryl, oxo, CO(R22), CON(R23)(R24), hydroxy, N(R27)(R28) or SO₂CH₃;

preferably independently of one another H, (C₁-C₈)-alkyl, —

(CR13R14)_n—

, R12, (C₁-C₄)-alkoxy-(C₁-C₄)-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 (C₁-C₆)-alkyl, O-(C₁-C₄)-alkyl, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, hydroxy-(C₁-C₄)-alkyl, (C₀-C₂)-alkylene-aryl, oxo, CO(R22), CON(R23)(R24), hydroxy or N(R27)(R28);

very particularly preferably independently of one another H, (C₁-C₈)-alkyl, or R1 and R2 form together with the nitrogen atom to which they are bonded a 5 to 6-membered monocyclic ring which, apart from the nitrogen atom, may include 0 to 1 additional heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the heterocyclic ring system may additionally be substituted by (C₁-C₆)-alkyl;

especially preferably independently of one another H, (C₁-C₈)-alkyl;

o 0, 1, 2, 3, 4;

R22, R23, R24, R27, R28 independently of one another H, (C₁-C₆)-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-(C₁-C₆)-alkyl, oxygen and sulfur;

R12 OH, O-(C₁-C₆)-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, CF₃, CN, oxo, (C₁-C₆)-alkyl, (C₀-C₂)-alkylene-aryl, N(R34)(R35), COO(R36), CO(C₁-C₆)-alkyl;

R34, R35 independently of one another H, (C₁-C₄)-alkyl;

R36 H, (C₁-C₆)-alkyl, (C₀-C₂)-alkylene-aryl;

R13, R14 independently of one another H, (C₁-C₈)-alkyl, hydroxy-(C₁-C₄)-alkyl, OH, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl;

R38 H, F, Cl, Br, CF₃, CN, (C₁-C₆)-alkyl;

X a bond, CH₂CH₂, C(R76)(R77), N(R75), C═

C, (R75)YCH₂, CH₂—

NCO(R75), CH₂CON(R75);

Y O, S, N(R53), CO

R75, R76, R77 independently of one another H, (C₁-C₈)-alkyl;

R53 H, (C₁-C₈)-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, CF₃, OH, CN, OCF₃, O-(C₁-C₆)-alkyl, (C₁-C₆)-alkyl, SO₂—

CH₃, CO(R65);

R65 H, (C₁-C₈)-alkyl;

K O, a bond, CH₂O, CH₂, OCH₂, S, SO₂, N(R80), N(R81)CO, CON(R82), (C(R83)(R84))_v, CO, C≡

C, SCH₂, SO₂CH₂;

preferably 0, a bond, CH₂O, CH₂, OCH₂, N(R80), C≡

C;

v 1, 2, 3;

R80, R81, R82, R83, R84 independently of one another H, (C₁-C₈)-alkyl;

R11 (C₁-C₈)-alkyl, (C₁-C₄)-alkoxy-(C₁-C₄)-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, CF₃, CN, (C₁-C₆)-alkyl, O-(C₁-C₈)-alkyl, oxo, CO(R66), hydroxy, N(R70)CO(C₁-C₆)-alkyl, or SO₂CH₃;

R66, R70 independently of one another H, (C₁-C₈)-alkyl;

the N-oxides thereof and the physiologically tolerated salts thereof.

6. A compound of the formula I as claimed in any of claims 1 to 5,

in which

A, B, D, G are independently of one another N or C(R38), and the total number of nitrogen atoms in this ring is 0-2, preferably 0 or 1, and for the case where the total number of nitrogen atoms is 1, particularly preferably A or B are N and very particularly preferably B is N.

7. A compound of the formula I as claimed in any of claims 1 to 6,

in which

n is 1 and

m is 1 or 2.

8. A medicament comprising one or more of the compounds as claimed in any of claims 1 to 7.

9. A medicament comprising one or more of the compounds as claimed in any of claims 1 to 7 and one or more anorectic active ingredients.

10. A compound of the formula I as claimed in any of claims 1 to 7 for use as medicament for the prophylaxis or treatment of obesity.

11. A compound of the formula I as claimed in any of claims 1 to 7 for use as medicament for the prophylaxis or treatment of type 11 diabetes.

12. A compound of the formula I as claimed in any of claims 1 to 7 in combination with at least one further anorectic active ingredient for use as medicament for the prophylaxis or treatment of obesity.

13. A compound of the formula I as claimed in any of claims 1 to 7 in combination with at least one further anorectic active ingredient for use as medicament for the prophylaxis or treatment of type 11 diabetes.

14. A process for producing a medicament comprising one or more of the compounds of the formula I as claimed in any of claims 1 to 7, which comprises mixing the active ingredient with a pharmaceutically suitable carrier, and converting this mixture into a form suitable for administration.

15. The use of the compounds of the formula I as claimed in any of claims 1 to 7 for producing a medicament for weight reduction in mammals.

16. The use of the compounds of the formula I as claimed in any of claims 1 to 7 for producing a medicament for the prophylaxis or treatment of obesity.

17. The use of the compounds of the formula I as claimed in any of claims 1 to 7 for producing a medicament for the prophylaxis or treatment of type II diabetes.