Carbamate/urea derivatives containing piperidin and piperazin rings as h3 receptor inhibitors

A compound of the formula I

• or a salt thereof, wherein
• R1 is C1-6alkyl, C2-6alkenyl, C2-6alkinyl, C3-6cycloalkyl, C5-6cycloalkenyl or C3-6cycloalkyl-C1-4alkyl;
• wherein said C1-6alkyl, C2-6alkenyl, C2-6alkinyl or C3-6cycloalkyl-C1-4alkyl may be substituted once or more than once by halogen, hydroxyl or C1-4alkoxy;
• and wherein said C3-6cycloalkyl or C5-6cycloalkenyl may be substituted once or more than once by halogen, hydroxyl, C1-4alkyl, C1-4halogenalkyl, C1-4hydroxyalkyl or C1-4alkoxy;
• m is 1 or 2;
• n is 0, 1, 2, 3 or 4;
• each R2 independently is halogen, hydroxyl, amino, cyano, nitro, C1-6alkyl, C1-6halogenalkyl, C1-6hydroxyalkyl, C1-4alkoxy-C1-6alkyl, amino-C1-6alkyl, C1-4alkyl-amino-C1-6alkyl, di(C1-4alkyl)-amino-C1-6alkyl, C1-6alkoxy, C1-6halogenalkoxy, C1-6alkylamino, di(C1-6alkyl)amino, C2-6alkenyl, C2-6halogenalkenyl, C2-6alkinyl or C2-6halogenalkinyl;
• or C3-6cycloalkyl, wherein one carbon atom may be replaced by an oxygen atom, wherein the C3-6cycloalkyl may be attached directly to the methylene or via a C1-2alkylene, and wherein the C3-6cycloalkyl may be substituted once or more than once by halogen;
• or two R2 at the same carbon atom form together with said carbon atom a C3-6cycloalkyl;
• X1 is oxygen or —N(R4)—;
• R4 is hydrogen, C1-6alkyl, C3-6cycloalkyl, or C3-6cycloalkyl-C1-2alkyl;
• p is 1 and q is 1;
• p is 0 and q is 1;
• or
• p is 0 and q is 0;
• r is 0, 1, 2, 3 or 4;
• each R3 independently is halogen, hydroxyl, amino, cyano, nitro, C1-6alkyl, C1-6halogenalkyl, C1-6hydroxyalkyl, C1-4alkoxy-C1-6alkyl, amino-C1-6alkyl, C1-4alkyl-amino-C1-6alkyl, di(C1-4alkyl)-amino-C1-6alkyl, C1-6alkoxy, C1-6halogenalkoxy, C1-6alkylamino, di(C1-6alkyl)amino, C2-6alkenyl, C2-6halogenalkenyl, C2-6alkinyl or C2-6halogenalkinyl;
• or C3-6cycloalkyl, wherein one carbon atom may be replaced by an oxygen atom, wherein the C3-6cycloalkyl may be attached directly to the methylene or via a C1-2alkylene, and wherein the C3-6cycloalkyl may be substituted once or more than once by halogen;
• or two R3 at the same carbon atom form together with said carbon atom a C3-6cycloalkyl;
• A is a five- to six-membered monocyclic or an eight- to ten-membered fused bicyclic aromatic ring system, wherein said ring system may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, and wherein said ring system may be substituted once or more than once by R5;
• each R5 independently is halogen;
• cyano;
• nitro;
• hydroxy;
• amino;
• —C(O)H;
• —C(O)NH2;
• —C(O)OH;
• —X2—R6;
• or —X3—B1;
• X2 is selected from bond;
• carbonyl;
• oxygen;
• sulfur;
• —S(O)—;
• —S(O)2—;
• amino, which may be substituted by C1-4alkyl;
• —N(Ra)—C(O)—;
• —C(O)—N(Rb)—;
• —C(O)—O—;
• —O—C(O)—;
• —N(Rc)—S(O)2—;
• —S(O)2—N(Rd)—;
• and —NHC(O)NH—;
• Ra, Rb, Rc and Rd each independently is hydrogen or C1-4alkyl;
• R6 is C1-6alkyl;
• C1-6halogenalkyl;
• C1-6-cyanoalkyl;
• C1-6carboxyalkyl;
• C1-6hydroxyalkyl;
• C1-4alkoxy-C1-6alkyl;
• C1-4alkoxy-C1-4alkoxy-C1-6alkyl;
• C1-4alkylcarbonyl-C1-6alkyl;
• C1-4alkoxycarbonyl-C1-6alkyl;
• C1-4alkylcarbonyloxy-C1-6alkyl;
• C1-6aminoalkyl;
• C1-4alkylamino-C1-6alkyl;
• di(C1-4alkyl)amino-C1-6alkyl;
• aminocarbonyl-C1-6alkyl;
• C1-4alkylaminocarbonyl-C1-6alkyl;
• di(C1-4alkyl)aminocarbonyl-C1-6alkyl;
• C1-4alkylcarbonylamino-C1-6alkyl;
• C1-4alkylaminosulfonyl-C1-6alkyl;
• di(C1-4alkyl)aminosulfonyl-C1-6alkyl;
• C2-6alkenyl;
• C2-6halogenalkenyl;
• C2-6alkinyl;
• C2-6halogenalkinyl;
• X3 is bond or C1-3alkylene, wherein one carbon atom of the C1-3alkylene may be replaced by a group selected from carbonyl;
• oxygen;
• sulfur;
• —S(O)—;
• —S(O)2—;
• amino, which may be substituted by C1-4alkyl;
• N(Re)—C(O)—;
• —C(O)—N(Rf)—;
• —C(O)—O—;
• —O—C(O)—;
• —N(Rg)—S(O)2—;
• —S(O)2—N(Rh)—;
• and —NHC(O)NH—;
• Re, Rf, Rg and Rh each independently is hydrogen or C1-4alkyl;
• B1 is a three- to seven-membered monocyclic ring system which may be aromatic, saturated or unsaturated non-aromatic and which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein the ring system may in turn be substituted once or more than once by R7;
• each R7 independently is halogen, cyano, C1-4alkyl, C1-4halogenalkyl, C1-4alkoxy, or C1-4halogenalkoxy;
• or two R7 at the same ring atom together are oxo;
• or two R5 at adjacent ring atoms form together with said ring atoms a fused five- to seven-membered monocyclic unsaturated non-aromatic ring system which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein the ring system may in turn be substituted once or more than once by R8, and wherein each R8 independently is halogen, C1-4alkyl or C1-4alkoxy, or two R8 at the same ring atom together are oxo;
• and provided that the compounds
• N-[(3R)-1-[7-[[(2,4-dichlorophenyl)methyl]amino]pyrazolo[1,5-a]pyrimidin-5-yl]-3-pyrrolidinyl]-4-methyl-1-piperazinecarboxamide;
• 4-cyclopentyl-N-[1-[5-(trifluoromethyl)-2-pyridinyl]-3-azetidinyl]-1-piperazinecarboxamide;
• 4-cyclopentyl-N-[1-[5-(trifluoromethyl)-2-pyridinyl]-3-pyrrolidinyl]-1-piperazinecarboxamide;
• 4-(1,1-dimethylethyl)hexahydro-N-[1-(2-pyrimidinyl)-4-piperidinyl]-1H-1,4-diazepine-1-carboxamide;
• 4-ethyl-N-[1-(2-pyrimidinyl)-4-piperidinyl]-1-piperazinecarboxamide;
• hexahydro-4-methyl-N-[1-(2-pyrimidinyl)-4-piperidinyl]-1H-1,4-diazepine-1-carboxamide;
• 4-(2,2-difluoroethyl)-N-[1-(2-pyrimidinyl)-4-piperidinyl]-1-piperazinecarboxamide;
• N-(1-(4-acetylphenyl)piperidin-4-yl)-4-cyclopentyl piperazine-1-carboxamide;
• and
• N-(1-(4-acetylphenyl)piperidin-4-yl)-4-cyclobutylpiperazine-1-carboxamide are excluded.