Amino substituted dibenzothiophene derivatives for the treatment of disorders mediated by np y5 receptor

A compound of formula (I) selected from:

• 2-(N′-pyrid-4-ylethyl-N′-methylureido)dibenzothiophene;
• 5,5-dioxo-2-(N′-pyrid-4-ylethyl-N′-methylureido)dibenzothiophene;
• 5,5-dioxo-2-[4-(pyrid-4-yl)piperidin-1-ylcarbonylamino]dibenzothiophene;
• 5,5-dioxo-2-[4-(pyrid-2-yl)piperidin-1-ylcarbonylamino]dibenzothiophene;
• 5,5-dioxo-2-(N′-phenethyl-N′-methylureido)dibenzothiophene;
• 5,5-dioxo-2-(4,4,4-trifluoro-2-methylbutyrylamino)dibenzothiophene;
• 5,5-dioxo-2-[4-(2,3,5,6-tetrafluoropyrid-4-yl)piperazin-1-ylcarbonylamino]dibenzothiophene;
• or a pharmaceutically acceptable salt, prodrug or solvate thereof.

A compound of formula (IA′):

• 202
• wherein:
• X is a group of formula (A) or (B):
• 203
• R1 is cyano, halo, trifluoromethyl, trifluoromethoxy, C1-4alkyl, C1-4alkoxy, N-(C1-4alkyl)amino or N,N-(C1-4alkyl)2amino;
• R2 is halo, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, C1-4alkyl or C1-4alkoxy;
• A is —NRa— or a direct bond;
• wherein Ra is hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl;
• wherein Ra may be optionally substituted by one or more R5;
• R3 is hydrogen, C1-10alkyl, C2-10alkenyl or C2-10alkynyl wherein R3 may be optionally substituted by one or more R6;
• or R3 is carbocyclyl or heterocyclyl wherein R3 may be optionally substituted on carbon by one or more R7;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by R8;
• R4 is halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-4alkoxycarbonyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkanoyloxy, N-(C1-4alkyl)amino, N,N-(C1-4alkyl)2amino, C1-4alkanoylamino, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, N-(carbocyclyl)carbamoyl, N,N-(carbocyclyl)2carbamoyl, N-(heterocyclyl)carbamoyl, N,N-(heterocyclyl)2carbamoyl, C1-4alkylS(O)a wherein a is 0 to 2, C1-4alkoxycarbonyl, N-(C1-4alkyl)sulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, C1-4alkylsulphonylamino or (nitrogen-linked heterocyclic ring)carbonyl;
• R5 and R6 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, aminosulphamoyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, C1-6alkanoylamino, C2-6alkenyloxycarbonyl, C1-6alkoxycarbonyl, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclyl-N-(C1-6alkyl)amino, heterocyclylsulphonyl, heterocyclylcarbonyl, heterocyclylcarbonylamino, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylamino, carbocyclyl-N-(C1-6alkyl)amino, carbocyclylsulphonyl, carbocyclylcarbonyl, carbocyclylcarbonylamino, carbocyclyloxycarbonyl, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C1-6alkoxycarbonylamino, N-(C1-6alkyl)carbamoyl, N,N-(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0-2, N-(C1-6alkyl)sulphamoylamino, N,N-(C1-6alkyl)2sulphamoylamino, C1-6alkylsulphonylamino, (C1-6alkyl)sulphonyl-N-(C1-6alkyl)amino, N-(C1-6alkyl)sulphamoyl and N,N-(C1-6alkyl)2sulphamoyl;
• wherein R5 and R6 may be optionally substituted on carbon by one or more R9;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be independently optionally substituted by R10;
• R7 and R9 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, trifluoromethyl, trifluoromethoxy, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, aminosulphamoyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, C2-4alkenyloxycarbonyl, C1-4alkanoyl, C1-4alkanoylamino, C1-4alkanoyloxy, N-(C1-4alkyl)amino, N. N-(C1-4alkyl)2amino, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, C1-4alkylS(O)a wherein a is 0-2, N-(C1-4alkyl)sulphamoylamino, N,N-(C1-4alkyl)2sulphamoylamino, (C1-4alkyl)sulphonylamino, (C1-4alkyl)sulphonyl-N-(C1-4alkyl)amino, N-(C 1-4alkyl)sulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclyl-N-(C1-4alkyl)amino, heterocyclylsulphonyl, heterocyclylcarbonyl, heterocyclylcarbonylamino, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylamino, carbocyclyl-N-(C1-4alkyl)amino, carboocyclylsulphonyl, carbocyclylcarbonyl, carbocyclylcarbonylamino, and carbocyclyloxycarbonyl;
• wherein R7 and R9 may be independently optionally substituted on carbon by one or more R11;
• R8 and R10 are independently selected from C1-4alkyl, C1-4alkanoyl, sulphamoyl, C1-4alkylsulphonyl, C1-4alkoxycarbonyl, carbamoyl, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, N-(C1-4alkyl)sulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, heterocyclyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylsulphonyl, carbocyclyl, carbocyclylcarbonyl, carbocyclyloxycarbonyl and carbocyclylsulphonyl;
• wherein R8 and R10 may be independently optionally substituted on carbon by one or more R12;
• R11 and R12 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, methyl, ethyl, vinyl, allyl, methoxy, ethoxy, vinyloxy, allyloxy, methoxycarbonyl, formyl, acetyl, formamido, acetylamino, acetoxy, methylamino, dimethylamino, N-methylcarbamoyl, N,N-dimethylcarbamoyl, methylthio, methylsulphinyl, mesyl, N-methylsulphamoyl, N,N-dimethylsulphamoyl, heterocyclyl, heterocyclyloxy, heterocyclylcarbonyl, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylcarbonyl and carbocyclyloxycarbonyl;
• x is 0-4;
• wherein the values of R1 may be the same or different;
• y is 0-3;
• wherein the values of R2 may be the same or different;
• z is 0-3;
• wherein the values of R4 may be the same or different;
• and
• n is 0-2;
• or a pharmaceutically acceptable salt, prodrug or solvate thereof;
• with the provisos when X is a group of formula (A):
• 1) when R3 is a nitrogen linked heterocyclyl, A is a direct bond;
• 2) when x and y are 0 and n is 2, the group R3-A-C(O)—NH— is not 2-formamido, 2-acetamido, 2-propionamido, 2-(2-pthalimidoacetamido), 2-(3-pthalimidopropionamido), 2-(2-pthalimido-2-isopropylacetamido), 2-(2-pthalimido-2-isobutylacetamido), 2-(2-pthalimido-2-benzylacetamido), 2-(2-aminoacetamido), 2-(3-aminopropionamido), 2-(2-amino-2-isopropylacetamido), 2-(2-amino-2-isobutylacetamido), 2-(2-amino-2-benzylacetamido), 3-(2-pthalimidoacetamido), 3-(3-pthalimidopropionamido), 3-(2-pthalimido-2-isopropylacetamido), 3-(2-pthalimido-2-isobutylacetamido), 3-(2-pthalimido-2-benzylacetamido), 3-(2-aminoacetamido), 3-(3-aminopropionamido), 3-(2-amino-2-isopropylacetamido), 3-(2-amino-2-benzylacetamido) or 2-(3,3,3-trifluoro-2-hydroxy-2-methylpropionamido);
• 3) when x and y are 0 and n is 1, the group R3-A-C(O)—NH— is not 3-(2-pthalimidoacetamido), 3-(3-pthalimidopropionamido), 3-(2-pthalimido-2-isopropylacetamido), 3-(2-pthalimido-2-isobutylacetam-ido), 3-(2-pthalimido-2-benzylacetamido), 3-(2-aminoacetamido), 3-(3-aminopropionamido), 3-(2-amino-2-isopropylacetamido), 3-(2-amino-2-isobutylacetamido) or 3-(2-amino-2-benzylacetamido);
• 4) when x and y are 0 and n is 0, the group R3-A-C(O)—NH— is not 2-(2-pthalimidoacetamido), 2-(3-pthalimidopropionamido), 2-(2-pthalimido-2-isopropylacetamido), 2-(2-pthalimido-2-isobutylacetamido), 2-(2-pthalimido-2-benzylacetamido), 2-(2-aminoacetamido), 2-(3-aminopropionamido), 2-(2-amino-2-isopropylacetamido), 2-(2-amino-2-isobutylacetamido) or 2-(2-amino-2-benzylacetamido);
• 5) when (R1)X is 7-fluoro, y is 0 and n is 2, the group R3-A-C(O)—NH— is not 3-acetamido;
• or a pharmaceutically acceptable salt, prodrug or solvate thereof, for use as a medicament.

A method of treating disorders mediated by the neuropeptide Y5 receptor in a warm-blooded animal, such as a human being, in need of such treatment which comprises administering to said animal a therapeutically effective amount of a compound of formula (IB′):

• 204
• wherein:
• X is a group of formula (A) or (B):
• 205
• R1 is cyano, halo, trifluoromethyl, trifluoromethoxy, C1-4alkyl, C1-4alkoxy, N-(C1-4alkyl)amino or N,N-(C1-4alkyl)2amino;
• R2 is halo, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, C1-4alkyl or C1-4alkoxy;
• A is —NRa—, —O— or a direct bond;
• wherein Ra is hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl;
• wherein Ra may be optionally substituted by one or more R5;
• R3 is hydrogen, C1-10alkyl, C2-10alkenyl or C2-10alkynyl wherein R3 may be optionally substituted by one or more R6;
• or R3 is carbocyclyl or heterocyclyl wherein R3 may be optionally substituted on carbon by one or more R7;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by R8;
• R4 is halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-4alkoxycarbonyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C4alkanoyl, C1-4alkanoyloxy, N-(C1-4alkyl)amino, N,N-(C1-4alkyl)2amino, C1-4alkanoylamino, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, N-(carbocyclyl)carbamoyl, N,N-(carbocyclyl)2carbamoyl, N-(heterocyclyl)carbamoyl, N,N-(heterocyclyl)2carbamoyl, C1-4alkylS(O)a wherein a is 0 to 2, C1-4alkoxycarbonyl, N-(C1-4alkyl)sulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, C1-4alkylsulphonylamino or (nitrogen-linked heterocyclic ring)carbonyl;
• R5 and R6 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, aminosulphamoyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, C1-6alkanoylamino, C2-6alkenyloxycarbonyl, C1-6alkoxycarbonyl, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclyl-N-(C1-6alkyl)amino, heterocyclylsulphonyl, heterocyclylcarbonyl, heterocyclylcarbonylamino, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylamino, carbocyclyl-N-(C1-6alkyl)amino, carbocyclylsulphonyl, carbocyclylcarbonyl, carbocyclylcarbonylamino, carbocyclyloxycarbonyl, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C1-6alkoxycarbonylamino, N-(C1-6alkyl)carbamoyl, N,N-(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0-2, N-(C1-6alkyl)sulphamoylamino, N,N-(C1-6alkyl)2sulphamoylamino, C1-6alkylsulphonylamino, (C1-6alkyl)sulphonyl-N-(C1-6alkyl)amino, N-(C1-6alkyl)sulphamoyl and N,N-(C1-6alkyl)2sulphamoyl;
• wherein R5 and R6 may be optionally substituted on carbon by one or more R9;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be independently optionally substituted by R10;
• R7 and R9 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, trifluoromethyl, trifluoromethoxy, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, aminosulphamoyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, C2-4alkenyloxycarbonyl, C1-4alkanoyl, C1-4alkanoylamino, C1-4alkanoyloxy, N-(C1-4alkyl)amino, N,N-(C1-4alkyl)2amino, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, C1-4alkylS(O)a wherein a is 0-2, N-(C1-4alkyl)sulphamoylamino, N,N-(C1-4alkyl)2sulphamoylamino, (C1-4alkyl)sulphonylamino, (C1-4alkyl)sulphonyl-N-(C1-4alkyl)amino, N-(C1-4alkyl)sulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclyl-N-(C1-4alkyl)amino, heterocyclylsulphonyl, heterocyclylcarbonyl, heterocyclylcarbonylamino, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylamino, carbocyclyl-N-(C1-4alkyl)amino, carboocyclylsulphonyl, carbocyclylcarbonyl, carbocyclylcarbonylamino, and carbocyclyloxycarbonyl;
• wherein R7 and R9 may be independently optionally substituted on carbon by one or more R11;
• R8 and R10 are independently selected from C1-4alkyl, C1-4alkanoyl, sulphamoyl, C1-4alkylsulphonyl, C1-4alkoxycarbonyl, carbamoyl, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, N-(C1-4alkyl)sulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, heterocyclyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylsulphonyl, carbocyclyl, carbocyclylcarbonyl, carbocyclyloxycarbonyl and carbocyclylsulphonyl;
• wherein R8 and R10 may be independently optionally substituted on carbon by one or more R12;
• R11 and R12 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, methyl, ethyl, vinyl, allyl, methoxy, ethoxy, vinyloxy, allyloxy, methoxycarbonyl, formyl, acetyl, formamido, acetylamino, acetoxy, methylamino, dimethylamino, N-methylcarbamoyl, N,N-dimethylcarbamoyl, methylthio, methylsulphinyl, mesyl, N-methylsulphamoyl, N,N-dimethylsulphamoyl, heterocyclyl, heterocyclyloxy, heterocyclylcarbonyl, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylcarbonyl and carbocyclyloxycarbonyl;
• x is 0-4;
• wherein the values of R1 may be the same or different;
• y is 0-3;
• wherein the values of R2 may be the same or different;
• z is 0-3;
• wherein the values of R4 may be the same or different;
• and
• n is 0-2;
• with the providing that when R3 is a nitrogen linked heterocyclyl, A is a direct bond;
• or a pharmaceutically acceptable salt, prodrug or solvate thereof.

A method for promoting weight loss in a warm-blooded animal in need of such treatment, which comprises administering to said animal a therapeutically effective amount of a compound of formula (IB′):

• 206
• wherein:
• X is a group of formula (A) or (B):
• 207
• R1 is cyano, halo, trifluoromethyl, trifluoromethoxy, C1-4alkyl, C1-4alkoxy, N-(C1-4alkyl)amino or N,N-(C1-4alkyl)2 amino;
• R2 is halo, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, C1-4alkyl or C1-4alkoxy;
• A is —NRa—, —O— or a direct bond;
• wherein Ra is hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl;
• wherein Ra may be optionally substituted by one or more R5;
• R3 is hydrogen, C1-10alkyl, C2-10alkenyl or C2-10alkynyl wherein R3 may be optionally substituted by one or more R6;
• or R3 is carbocyclyl or heterocyclyl wherein R3 may be optionally substituted on carbon by one or more R7;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by R8;
• R4 is halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-4alkoxycarbonyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkanoyloxy, N-(C1-4alkyl)amino, N,N-(C1-4alkyl)2amino, C1-4alkanoylamino, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, N-(carbocyclyl)carbamoyl, N,N-(carbocyclyl)2carbamoyl, N-(heterocyclyl)carbamoyl, N,N-(heterocyclyl)2carbamoyl, C1-4alkylS(O)a wherein a is 0 to 2, C1-4alkoxycarbonyl, N-(C1-4alkyl)sulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, C1-4alkylsulphonylamino or (nitrogen-linked heterocyclic ring)carbonyl;
• R5 and R6 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, aminosulphamoyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, C1-6alkanoylamino, C2-6alkenyloxycarbonyl, C1-6alkoxycarbonyl, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclyl-N-(C1-6alkyl)amino, heterocyclylsulphonyl, heterocyclylcarbonyl, heterocyclylcarbonylamino, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylamino, carbocyclyl-N-(C1-6alkyl)amino, carbocyclylsulphonyl, carbocyclylcarbonyl, carbocyclylcarbonylamino, carbocyclyloxycarbonyl, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C1-6alkoxycarbonylamino, N-(C1-6alkyl)carbamoyl, N,N-(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0-2, N-(C1-6alkyl)sulphamoylamino, N,N-(C1-6alkyl)2sulphamoylamino, C1-6alkylsulphonylamino, (C1-6alkyl)sulphonyl-N-(C1-6alkyl)amino, N-(C1-6alkyl)sulphamoyl and N,N-(C1-6alkyl)2sulphamoyl;
• wherein R5 and R6 may be optionally substituted on carbon by one or more R9;
• and wherein if said heterocyclyl contains an —NH— moiety, that nitrogen may be independently optionally substituted by R10;
• R7 and R9 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, trifluoromethyl, trifluoromethoxy, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, aminosulphamoyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, C2-4alkenyloxycarbonyl, C1-4alkanoyl, C1-4alkanoylamino, C1-4alkanoyloxy, N-(C1-4alkyl)amino, N,N-(C1-4alkyl)2amino, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, C1-4alkylS(O)a wherein a is 0-2, N-(C1-4alkyl)sulphamoylamino, N,N-(C1-4alkyl)2sulphamoylamino, (C1-4alkyl)sulphonylamino, (C1-4alkyl)sulphonyl-N-(C1-4alkyl)amino, N-(C1-4alkyl)sulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclyl-N-(C1-4alkyl)amino, heterocyclylsulphonyl, heterocyclylcarbonyl, heterocyclylcarbonylamino, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylamino, carbocyclyl-N-(C1-4alkyl)amino, carboocyclylsulphonyl, carbocyclylcarbonyl, carbocyclylcarbonylamino, and carbocyclyloxycarbonyl;
• wherein R7 and R9 may be independently optionally substituted on carbon by one or more R11;
• R8 and R10 are independently selected from C1-4alkyl, C1-4alkanoyl, sulphamoyl, C1-4alkylsulphonyl, C1-4alkoxycarbonyl, carbarnoyl, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, N-(C1-4alkyl)sulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, heterocyclyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylsulphonyl, carbocyclyl, carbocyclylcarbonyl, carbocyclyloxycarbonyl and carbocyclylsulphonyl;
• wherein R8 and R10 may be independently optionally substituted on carbon by one or more R12;
• R11 and R12 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, methyl, ethyl, vinyl, allyl, methoxy, ethoxy, vinyloxy, allyloxy, methoxycarbonyl, formyl, acetyl, formamido, acetylamino, acetoxy, methylamino, dimethylamino, N-methylcarbamoyl, N,N-dimethylcarbamoyl, methylthio, methylsulphinyl, mesyl, N-methylsulphamoyl, N,N-dimethylsulphamoyl, heterocyclyl, heterocyclyloxy, heterocyclylcarbonyl, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylcarbonyl and carbocyclyloxycarbonyl;
• x is 0-4;
• wherein the values of R1 may be the same or different;
• y is 0-3;
• wherein the values of R2 may be the same or different;
• z is 0-3;
• wherein the values of R4 may be the same or different;
• and
• n is 0-2;
• with the proviso that when R3 is a nitrogen linked heterocyclyl, A is a direct bond;
• or a pharmaceutically acceptable salt, prodrug or solvate thereof

A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier in association with a compound of formula (IB′):

• 208
• wherein:
• X is a group of formula (A) or (B):
• 209
• R1 is cyano, halo, trifluoromethyl, trifluoromethoxy, C1-4alkyl, C1-4alkoxy, N-(C1-4alkyl)amino or N,N-(C1-4alkyl)2amino;
• R2 is halo, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, C1-4alkyl or C1-4alkoxy;
• A is —NRa—, —O— or a direct bond;
• wherein Ra is hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl;
• wherein Ra may be optionally substituted by one or more R5;
• R3 is hydrogen, C1-10alkyl, C2-10alkenyl or C2-10alkynyl wherein R3 may be optionally substituted by one or more R6;
• or R3 is carbocyclyl or heterocyclyl wherein R3 may be optionally substituted on carbon by one or more R7;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by R8;
• R4 is halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-4alkoxycarbonyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkanoyloxy, N-(C1-4alkyl)amino, N,N-(C1-4alkyl)2amino, C1-4alkanoylamino, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, N-(carbocyclyl)carbamoyl, N,N-(carbocyclyl)2carbamoyl, N-(heterocyclyl)carbamoyl, N,N-(heterocyclyl)2carbamoyl, C1-4alkylS(O)a wherein a is 0 to 2, C1-4alkoxycarbonyl, N-(C1-4alkyl)sulpbamoyl, N,N-(C1-4alkyl)2sulphamoyl, C1-4alkylsulphonylamino or (nitrogen-linked heterocyclic ring)carbonyl;
• R5 and R6 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, aminosulphamoyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, C1-6alkanoylamino, C2-6alkenyloxycarbonyl, C1-6alkoxycarbonyl, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclyl-N-(C1-6alkyl)amino, heterocyclylsulphonyl, heterocyclylcarbonyl, heterocyclylcarbonylamino, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylamino, carbocyclyl-N-(C1-6alkyl)amino, carbocyclylsulphonyl, carbocyclylcarbonyl, carbocyclylcarbonylamino, carbocyclyloxycarbonyl, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C1-6alkoxycarbonylamino, N-(C1-6alkyl)carbamoyl, N,N-(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0-2, N-(C1-6alkyl)sulphamoylamino, N,N-(C1-6alkyl)2sulphamoylamino, C1-6alkylsulphonylamino, (C1-6alkyl)sulphonyl-N-(C1-6alkyl)amino, N-(C1-6alkyl)sulphamoyl and N,N-(C1-6alkyl)2sulphamoyl;
• wherein R5 and R6 may be optionally substituted on carbon by one or more R9;
• and wherein if said heterocyclyl contains an —NH— moiety, that nitrogen may be independently optionally substituted by R10;
• R7 and R9 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, trifluoromethyl, trifluoromethoxy, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, aminosulphamoyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, C2-4alkenyloxycarbonyl, C1-4alkanoyl, C1-4alkanoylamino, C1-4alkanoyloxy, N-(C1-4alkyl)amino, N,N-(C1-4alkyl)2amino, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, C1-4alkylS(O)a wherein a is 0-2, N-(C1-4alkyl)sulphamoylamino, N,N-(C1-4alkyl)2sulphamoylamino, (C1-4alkyl)sulphonylamino, (C1-4alkyl)sulphonyl-N-(C1-4alkyl)amino, N-(C1-4alkyl)sulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclyl-N-(C1-4alkyl)amino, heterocyclylsulphonyl, heterocyclylcarbonyl, heterocyclylcarbonylamino, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylamino, carbocyclyl-N-(C1-4alkyl)amino, carboocyclylsulphonyl, carbocyclylcarbonyl, carbocyclylcarbonylamino, and carbocyclyloxycarbonyl;
• wherein R7 and R9 may be independently optionally substituted on carbon by one or more R11;
• R8 and R10 are independently selected from C1-4alkyl, C1-4alkanoyl, sulphamoyl, C1-4alkylsulphonyl, C1-4alkoxycarbonyl, carbamoyl, N-(C1-4alkyl)carbamoyl, N,N-(C1-4alkyl)2carbamoyl, N-(C1-4alkyl)sulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, heterocyclyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylsulphonyl, carbocyclyl, carbocyclylcarbonyl, carbocyclyloxycarbonyl and carbocyclylsulphonyl;
• wherein R8 and R10 may be independently optionally substituted on carbon by one or more R12;
• R11 and R12 are independently selected from halo, hydroxy, cyano, carbamoyl, ureido, amino, nitro, carboxy, carbamoyl, mercapto, sulphamoyl, methyl, ethyl, vinyl, allyl, methoxy, ethoxy, vinyloxy, allyloxy, methoxycarbonyl, formyl, acetyl, formamido, acetylamino, acetoxy, methylamino, dimethylamino, N-methylcarbamoyl, N,N-dimethylcarbamoyl, methylthio, methylsulphinyl, mesyl, N-methylsulphamoyl, N,N-dimethylsulphamoyl, heterocyclyl, heterocyclyloxy, heterocyclylcarbonyl, heterocyclyloxycarbonyl, carbocyclyl, carbocyclyloxy, carbocyclylcarbonyl and carbocyclyloxycarbonyl;
• x is 0-4;
• wherein the values of R1 may be the same or different;
• y is 0-3;
• wherein the values of R2 may be the same or different;
• z is 0-3;
• wherein the values of R4 may be the same or different;
• and
• n is 0-2;
• with the proviso that when R3 is a nitrogen linked heterocyclyl, A is a direct bond;
• or a pharmaceutically acceptable salt, prodrug or solvate thereof.