Substituted amino heterocycles as vr-1 antagonists for treating pain

A compound of formula 1:

• wherein:
• one of T1 and T4 is N and the other is C;
• T2 and T3 are independently N or C(CH2)nR2;
• X, Y and Z are independently N or C(CH2)nR3;
• R1 is Ar1 or R1 is C1-6alkyl optionally substituted with one or two groups Ar1;
• Ar1 is cyclohexyl, piperidinyl, piperazinyl, morpholinyl, adamantyl, phenyl, naphthyl, a six-membered heteroaromatic ring containing one, two or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, three or four heteroatoms chosen from O, N and S, at most one O or S atom being present, or a nine- or ten-membered bicyclic heteroaromatic ring in which phenyl or a six-membered heteroaromatic ring as defined above is fused to a six- or five-membered heteroaromatic ring as defined above;
• Ar1 is optionally substituted by one, two or three groups chosen from halogen, hydroxy, cyano, nitro, isonitrile, CF3, OCF3, SF5, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylthio, C1-6alkylsulfinyl, C1-6alkylsulfonyl, —NR6R7, CONR6R7, —COH, —C12H, C1-6alkylcarbonyl, C1-6alkoxycarbonyl, haloC1-6alkyl, haloC2-6alkenyl, hydroxyC1-6alkyl, aminoC1-6alkyl, cyanoC1-6alkyl, C3-6cycloalkyl, hydroxyC3-6cycloalkyl, aminoC3-6cycloalkyl, haloC3-6cycloalkyl, cyanoC3-6cycloalkyl, haloC1-6alkylcarbonyl, C1-6alkoxycarbonylC1-6alkyl, (halo)(hydroxy)C1-6alkyl, (halo)(hydroxy)C3-6cycloalkyl, phenyl and a five-membered heteroaromatic ring containing one, two or three heteroatoms, at most one O or S atom being present;
• wherein the phenyl and five-membered heteroaromatic ring are optionally substituted by C1-6alkyl, halo, hydroxy or cyano;
• when two C1-6alkyl groups substitute adjacent positions on Ar1 then, together with the carbon atoms to which they are attached, they may form a partially saturated ring containing five or six carbon atoms;
• when two C1-6alkoxy groups substitute adjacent positions on Ar1 then, together with the carbon atoms to which they are attached, they may form a partially saturated five- or six-membered ring;
• Ar is phenyl, a six-membered heteroaromatic ring containing one, two or three nitrogen atoms or a five-membered heteroaromatic ring containing one, two, three or four heteroatoms chosen from O, N and S, at most one heteroatom being O or S, Ar being optionally substituted by one, two or three groups chosen from halogen, CF3, OCF3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, nitro, cyano, isonitrile, hydroxy, C1-6alkoxy, C1-6alkylthio, —NR6R7, —CONR6R7, —COH, CO2H, C1-6alkoxycarbonyl, haloC1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, C1-6alkylcarbonyl and a five-membered heteroaromatic ring containing one, two, three or four heteroatoms chosen from O, N and S, at most one heteroatom being O or S, optionally substituted by C1-6alkyl, halogen, amino, hydroxy or cyano;
• R2 and R3 are independently hydrogen, halogen, CF3, OCF3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, nitro, cyano, isonitrile, hydroxy, C1-6alkoxy, C1-6alkylthio, —NR6R7, —CONR6R7, —COH, CO2H, C1-6alkoxycarbonyl, haloC1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, C1-6alkylaminoC1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl, amido, piperidinyl, piperazinyl, C3-6cycloalkyl, morpholinyl, phenyl, a six-membered heteroaromatic ring containing one, two or three nitrogen atoms or a five-membered heteroaromatic ring containing one, two, three or four heteroatoms chosen from O, N and S, at most one O or S atom being present, which phenyl, six-membered heteroaromatic ring and five-membered heteraromatic ring are optionally substituted by haloC1-6alkyl, C1-6alkyl, hydroxy, halogen, amino or cyano;
• R6 and R7 are independently hydrogen or C1-6alkyl;
• when both R6 and R7 are C1-6alkyl then, together with the nitrogen atom to which they are attached, they may form a five or six membered saturated nitrogen containing ring;
• and
• n is zero, one, two or three;
• or a pharmaceutically acceptable salt thereof.