Amide compounds having MCH-antagonistic activity and medicaments comprising these compounds

An amide compound of formula I

• wherein
• R1, R2 independently of one another denote H, a C1-8-alkyl or C3-7-cycloalkyl group optionally substituted by the group R11, while a —CH2— group in position 3 or 4 of a 5-, 6- or 7-membered cycloalkyl group may be replaced by —O—, —S— or —NR13—, or a phenyl or pyridinyl group optionally mono- or polysubstituted by the group R12 and/or monosubstituted by nitro, with the proviso that at least one of the groups R1, R2 has a meaning other than H, or
• R1 and R2 form a C2-8-alkylene bridge wherein
• one or two —CH2— groups may be replaced independently of one another by —CH═N— or —CH═CH— and/or
• one or two —CH2— groups may be replaced independently of one another by —O—, —S—, —SO—, —(SO2)—, —C═N—O—R18—, —CO—, —C(═CH2)— or —NR13— in such a way that heteroatoms are not directly connected to one another,
• while in the above-defined alkylene bridge one or more H atoms may be replaced by R14, and
• while the above-defined alkylene bridge may be substituted by one or two identical or different carbo- or heterocyclic groups Cy in such a way that the bond between the alkylene bridge and the group Cy is formed
• via a single or double bond,
• via a common C atom forming a spirocyclic ring system,
• via two common, adjacent C and/or N atoms forming a fused bicyclic ring system or
• via three or more C and/or N atoms forming a bridged ring system,
• R3 denotes H, C1-6-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-4-alkyl,
• X denotes a C1-4-alkylene bridge and if the group Y is linked to X via a C atom, it may also denote —CH2—CH═CH—, —CH2—C≡C—, C2-4-alkylenoxy or C2-4-alkylene-NR4,
• while the bridge X may be attached to R1 including the N atom attached to R1 and X forming a heterocyclic group, and
• two C atoms or one C and one N atom of the alkylene bridge may be joined together by an additional C1-4-alkylene bridge, and
• a C atom may be substituted by R10 and/or one or two C atoms in each case may be substituted with one or two identical or different substituents selected from C1-6-alkyl, C3-7-cycloalkyl, and C3-7-cycloalkyl-C1-3-alkyl, while two alkyl substituents may be joined together, forming a carbocyclic ring system, and
• with the proviso that the group X with the meaning C2-4-alkyleneoxy has no hydroxy substituents;
• W is selected from among —CR6aR6b—O—, —CR7a═CR7c—, —CR6aR6b—NR8—, and —NR8—CR6aR6b—,
• Z denotes a single bond, C1-4-alkylene, wherein two adjacent C atoms may be joined together with an additional C1-4-alkylene bridge,
• while a C atom of the alkylene bridge may be substituted with R10 and/or one or two C atoms independently of one another may be substituted with one or two identical or different C1-6-alkyl groups, while two alkyl groups may be joined together, forming a carbocyclic ring, and
• Y is selected from among the following bivalent cyclic groups
• while the above-mentioned cyclic groups may be mono- or polysubstituted by R20 at one or more C atoms, and in the case of a phenyl group may also additionally be monosubstituted by nitro, and/or one or more NH group may be substituted by R21,
• A denotes one of the meanings given for Cy,
• B denotes one of the meanings given for Cy,
• b denotes the value 0 or 1,
• Cy denotes a carbo- or heterocyclic group selected from one of the following:
• a saturated 3- to 7-membered carbocyclic group,
• an unsaturated 4- to 7-membered carbocyclic group,
• a phenyl group,
• a saturated 4- to 7-membered or unsaturated 5- to 7-membered heterocyclic group with an N, O or S atom as heteroatom,
• a saturated or unsaturated 5- to 7-membered heterocyclic group with two or more N atoms or with one or two N atoms and an O or S atom as heteroatoms,
• an aromatic heterocyclic 5- or 6-membered group with one or more identical or different heteroatoms selected from N, O and/or S,
• while the above-mentioned 4-, 5-, 6- or 7-membered groups may be attached via two common, adjacent C atoms fused to a phenyl or pyridine ring, and
• in the above-mentioned 5-, 6- or 7-membered groups one or two non-adjacent —CH2— groups may be replaced independently of one another by a —CO—, —C(═CH2)—, —(SO)— or —(SO2)— group, and
• the above-mentioned saturated 6- or 7-membered groups may also be present as bridged ring systems with an imino, N-(C1-4-alkyl)-imino, methylene, C1-4-alkyl-methylene or di-(C1-4-alkyl)-methylene bridge, and the above-mentioned cyclic groups may be mono- or polysubstituted at one or more C atoms with R20, in the case of a phenyl group they may also additionally be monosubstituted with nitro, and/or one or more NH groups may be substituted with R21,
• R4 denotes H or C1-6-alkyl,
• R6aa, R6b denotes H, C1-4-alkyl or CF3,
• R7a, R7c, denotes H, F, C1-4-alkyl or CF3,
• R8 denotes H, C1-4-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-3-alkyl,
• R10 denotes hydroxy, ω-hydroxy-C1-3-alkyl, C1-4-alkoxy, ω-(C1-4-alkoxy)-C1-3-alkyl, C1-4-alkoxycarbonyl, amino, C1-4-alkyl-amino, di-(C1-4-alkyl)-amino, cyclo-C3-6-alkyleneimino, amino-C1-3-alkyl, C1-4-alkyl-amino-C1-3-alkyl, di-(C1-4-alkyl)-amino-C1-3-alkyl, cyclo-C3-6-alkyleneimino-C1-3-alkyl, amino-C1-3-alkoxy, C1-4-alkyl-amino-C1-3-alkoxy, di-(C1-4-alkyl)-amino-C1-3-alkoxy or cyclo-C3-6-alkyleneimino-C1-3-alkoxy, aminocarbonyl, C1-4-alkyl-aminocarbonyl, di-(C1-4-alkyl)-aminocarbonyl or cyclo-C3-6-alkyleneimino-carbonyl,
• R11 denotes C2-6-alkenyl, C2-6-alkynyl, R15—O, R15—O—CO, R15—CO—O, R16R17N, R18R19N—CO or Cy,
• R12 has one of the meanings given for R20,
• R13 has one of the meanings given for R17, with the exception of carboxy,
• R14 denotes halogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, R15—O, R15—O—CO, R15—CO, R15—CO—O, R16R17N, R18R19N—CO, R15—O—C1-3-alkyl, R15—O—CO—C1-3-alkyl, R15—O—CO—NH, R15—SO2—NH, R15—O—CO—NH—C1-3-alkyl-, R15—SO2—NH—C1-3-alkyl-, R15—CO—C1-3-alkyl, R15—CO—O—C1-3-alkyl, R16R17N—C1-3-alkyl, R18R19N—CO—C1-3-alkyl or Cy—C1-3-alkyl,
• R15 denotes H, C1-4-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, phenyl, phenyl-C1-3-alkyl, pyridinyl or pyridinyl-C1-3-alkyl,
• R16 denotes H, C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, C4-7-cycloalkenyl, C4-7-cycloalkenyl-C1-3-alkyl, ω-hydroxy-C2-3-alkyl, ω-(C1-4-alkoxy)-C2-3-alkyl, amino-C2-6-alkyl, C1-4-alkyl-amino-C2-6-alkyl, di-(C1-4-alkyl)-amino-C2-6-alkyl or cyclo-C3-6-alkyleneimino-C2-6-alkyl,
• R17 has one of the meanings given for R16 or denotes phenyl, phenyl-C1-3-alkyl, pyridinyl, dioxolan-2-yl, —CHO, C1-4-alkylcarbonyl, carboxy, hydroxycarbonyl-C1-3-alkyl, C1-4-alkoxycarbonyl, C1-4-alkoxycarbonyl-C1-3-alkyl, C1-4-alkylcarbonylamino-C2-3-alkyl, N-(C1-4-alkylcarbonyl)-N-(C1-4-alkyl)-amino-C2-3-alkyl, C1-4-alkylsulphonyl, C1-4-alkylsulphonylamino-C2-3-alkyl or N-(C1-4-alkylsulphonyl)-N(C1-4-alkyl)-amino-C2-3-alkyl,
• R18, R19 independently of one another denote H or C1-6-alkyl,
• R20 denotes halogen, hydroxy, cyano, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, hydroxy-C1-4-alkyl, R22—C1-3-alkyl or one of the meanings given for R22,
• R21 denotes C1-4-alkyl, ω-hydroxy-C2-3-alkyl, ω-C1-4-alkoxy-C2-6-alkyl, ω-C1-4-alkyl-amino-C2-6-alkyl, ω-di-(C1-4-alkyl)-amino-C2-6-alkyl, ω-cyclo-C3-6-alkyleneimino-C2-6-alkyl, phenyl-C1-3-alkyl, C1-4-alkyl-carbonyl, C1-4-alkoxy-carbonyl or C1-4-alkylsulphonyl,
• R22 denotes phenyl-C1-3-alkoxy, OHC, HO—N═HC, C1-4-alkoxy-N═HC, C1-4-alkoxy, C1-4-alkylthio, carboxy, C1-4-alkylcarbonyl, C1-4-alkoxycarbonyl, aminocarbonyl, C1-4-alkylamino-carbonyl, di-(C1-4-alkyl)-aminocarbonyl, cyclo-C3-6-alkyl-amino-carbonyl, cyclo-C3-6-alkyleneimino-carbonyl, cyclo-C3-6-alkyleneimino-C2-4-alkyl-aminocarbonyl, phenyl-amino-carbonyl, C1-4-alkyl-sulphonyl, C1-4-alkyl-sulphinyl, C1-4-alkyl-sulphonylamino, amino, C1-4-alkylamino, di-(C1-4-alkyl)-amino, C1-4-alkyl-carbonyl-amino, cyclo-C3-6-alkyleneimino, phenyl-C1-3-alkylamino or N-(C1-4-alkyl)-phenyl-C1-3-alkylamino, acetylamino, propionylamino, phenylcarbonylamino, phenylcarbonylmethylamino, (4-morpholinyl)carbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1-azepinyl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, methylenedioxy, or aminocarbonyl-amino,
• while in the above-mentioned groups and residues, in each case one or more C atoms may additionally be mono- or polysubstituted by F and/or in each case one or two C atoms may additionally be monosubstituted by Cl or Br independently of one another and/or in each case one or more phenyl rings may additionally, independently of one another, have one, two or three substituents selected from among F, Cl, Br, I, C1-4-alkyl, C1-4-alkoxy, difluoromethyl, trifluoromethyl, hydroxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, acetylamino, aminocarbonyl, cyano, difluoromethoxy, trifluoromethoxy, amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl- and di-(C1-3-alkyl)-amino-C1-3-alkyl and/or may be monosubstituted by nitro, and
• the H atom of any carboxy group present or an H atom bonded to an N atom may each be replaced by a group which can be cleaved in vivo,
• or a tautomer, the diastereomer, or enantiomers, thereof or mixtures thereof, or a salt thereof,
• with the following provisos (M1), and (M2)
• (M1) in the event that W denotes —CH═CH— and Y denotes a phenylene group and Z is a single bond, then the bridges X and Z at the phenylene ring of the group Y are in the para position to one another and at least one of the following conditions is met:
• (a) the group Y meaning phenylene is at least monosubstituted,
• (b) b has the value 0 and the group A is at least disubstituted,
• (c) b has the value 1;
• (M2) the following individual compounds are not included:
• 3-(4-chloro-phenyl)-N-{2-[4-(2-diethylamino-ethoxy)-phenyl]-ethyl}-acrylamide, N-{2-[3-(4-{2-[2-(4-chloro-phenoxy)-acetylamino]-ethyl}-phenoxy)-2-hydroxy -propylamino]-ethyl}-isobutyramide,
• cyclopentanecarboxylic acid {2-[3-(4-{2-[2-(4-chloro-phenoxy)-acetylamino]-ethyl}-phenoxy)-2-hydroxy-propylamino]-ethyl}-amide, and
• 2-(4-chloro-phenoxy)-N-(2-{4-[2-hydroxy-3-(2-phenylacetylamino-ethylamino)-propoxy]-phenyl}-ethyl)-acetamide.