β-ketoamide compounds with MCH antagonistic activity

A compound of formula I

• wherein:
• R1 and R2 form an alkylene bridge, such that R1R2N— denotes pyrrolidine, wherein in the alkylene bridge one or more H atoms are optionally replaced by R14, and the alkylene bridge is optionally independently substituted by one or two Cy groups such that the bond between the alkylene bridge and the Cy group is made via a single or double bond;
• R3 is H, C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-4-alkyl, or phenyl-C1-3-alkyl;
• X is a C1-8-alkylene bridge, wherein a —CH2— group which is not directly linked to the group R1R2N— is optionally replaced by —CH═CH— or —C≡C— wherein two C atoms of the bridge X are optionally joined together by an additional C1-4-alkylene bridge, and a C atom not directly connected to a heteroatom is optionally substituted by R10 and/or one or two C atoms are optionally independently substituted by one or two identical or different substituents selected from C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, C4-7-cycloalkenyl, and C4-7-cycloalkenyl-C1-3-alkyl, wherein two alkyl and/or alkenyl substituents are optionally joined together, forming a carbocyclic ring system;
• Z is a single bond or —CR7aR7b—CR7cR7d—;
• Y denotes indolyl, which may be mono- or polysubstituted at one or more C atoms by R20, and
• A denotes phenyl, which may be mono- or polysubstituted by R20 and may also additionally be monosubstituted by nitro;
• and
• B denotes phenyl, which may be mono- or polysubstituted by R20 and may also additionally be monosubstituted by nitro;
• and
• b has the value 0 or 1,
• Cy is 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 one 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, wherein the 4-, 5-, 6-, or 7-membered groups of Cy are optionally fused to a phenyl or pyridine ring via two common adjacent C atoms, and in the 5-, 6-, or 7-membered groups of Cy one or two non-adjacent —CH2 groups are optionally independently replaced by a —CO—, —C(═CH2)—, —(SO)—, or —(SO2)— group, and the saturated 6- or 7-membered groups of Cy are optionally 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 cyclic groups of Cy are optionally mono- or polysubstituted by R20 at one or more C atoms, and in the case of a phenyl group are optionally additionally monosubstituted by nitro, and/or one or more NH groups is optionally substituted by R21,
• R4 has one of the meanings given for R17 or denotes C3-6-alkenyl, or C3-6-alkynyl;
• R5a and R5b are each independently H, C1-3-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, CF3, F, or Cl, wherein if R5a and R5b are each an alkyl, they are optionally joined together such that a C3-7-cycloalkyl group is formed together with the C atom to which R5a and R5b are linked;
• R7a and R7c are each independently H, F, Cl, C1-4-alkyl, or CF3;
• R7b and R7d are each independently H, F, C1-4-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, or CF3,
• wherein if R7a and R7b are each alkyl, they are optionally joined together such that a C3-7-cycloalkyl group is formed together with the C atom to which R7a and R7b are linked, and/or if R7c and R7d are each alkyl, they are optionally joined together such that a C3-7-cycloalkyl group is formed together with the C atom to which R7c and R7d are linked, or R7b and R7d are each alkyl, they are optionally joined together such that a C3-7-cycloalkyl group is formed together with the two C atoms to which R7b and R7d are linked;
• R10 is hydroxy, hydroxy-C1-3-alkyl, C1-4-alkoxy, (C1-4-alkoxy)-C1-3-alkyl, carboxy, 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, cyclo-C3-6-alkyleneimino-C1-3-alkoxy, aminocarbonyl, C1-4-alkyl-aminocarbonyl, di-(C1-4-alkyl)-aminocarbonyl, or cyclo-C3-6-alkyleneimino-carbonyl;
• R11 is C1-3-alkyl, C2-6-alkenyl, C2-6-alkynyl, R15—O—, R15—O—C1-3-alkyl-, R15—O—CO—, R15—CO—O, cyano, R16R17N—, R18R19N—CO—, or Cy;
• R13 has one of the meanings given for R17;
• R14 is 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 is 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 is H, C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, C4-7-cycloalkenyl, C4-7-cycloalkenyl-C1-3-alkyl, hydroxy-C2-3-alkyl, 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, C1-4-alkylcarbonyl, hydroxy-carbonyl-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-alkylsulfonyl, C1-4-alkylsulfonylamino-C2-3-alkyl, or N—(C1-4-alkylsulfonyl)-N—(C1-4-alkyl)-amino-C2-3-alkyl-;
• R18 and R19 are each independently H or C1-6-alkyl;
• R20 is 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 has one of the meanings given for R22;
• R21 is C1-4-alkyl, hydroxy-C2-3-alkyl, C1-4-alkoxy-C2-6-alkyl, C1-4-alkyl-amino-C2-6-alkyl, di-(C1-4-alkyl)-amino-C2-6-alkyl, cyclo-C3-6-alkyleneimino-C2-6-alkyl, phenyl-C1-3-alkyl, C1-4-alkyl-carbonyl, C1-4-alkoxy-carbonyl, or C1-4-alkylsulfonyl;
• R22 is phenyl-C1-3-alkoxy, cyclo-C3-6-alkyleneimino-C2-4-alkoxy, 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-sulfonyl, C1-4-alkyl-sulfinyl, C1-4-alkyl-sulfonylamino, amino, C1-4-alkylamino, di-(C1-4-alkyl)-amino, C1-4-alkyl-carbonyl-amino, cyclo-C3-6-alkyleneimino, phenyl-C1-3-alkylamino, N—(C1-4-alkyl)-phenyl-C1-3-alkylamino, acetylamino, propionylamino, phenylcarbonylamino, phenylcarbonylmethylamino, hydroxy-C1-3-alkylaminocarbonyl, (4-morpholinyl)carbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1-azepinyl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, aminocarbonylamino, or C1-4-alkylaminocarbonylamino,
• wherein in each of the abovementioned groups and radicals one or more C atoms are optionally additionally mono- or polysubstituted by F and/or in each case one or two C atoms are optionally independently additionally monosubstituted by Cl or Br and/or one or more phenyl rings optionally independently additionally comprise one, two, or three substituents selected from the group 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 are optionally monosubstituted by nitro, and the H atom of a carboxy group or an H atom bound to an N atom are each optionally replaced by a group which can be cleaved in vivo,
• or a tautomer, enantiomer, salt, or mixture thereof.