Cancer treatment method comprising administering an erb-family inhibitor and a raf and/or ras inhibitor

1 . A method of treating a susceptible cancer in a mammal, comprising: administering to said mammal therapeutically effective amounts of (i) a compound of formula (I)

or a salt, solvate, physiologically functional derivative thereof,

wherein

Y is CR 1 and V is N:

or Y is CR 1 and V is CR 2 ;

R 1 represents a group CH 3 SO 2 CH 2 CH 2 NHCH 2 —Ar—, wherein Ar is selected from phenyl, furan, thiophene, Pyrrole and thiazole, each of which may optionally be substituted by one or two halo, C 1-4 alkyl or C 1-4 alkoxy groups:

R 2 is selected from the group comprising hydrogen, halo, hydroxy, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino and di[C 1-4 alkyl]amino:

U represents a phenyl, pyridyl, 3H-imidazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 1H-indazolyl, 2,3-dihydro-1H-indazolyl, 1H-benzimidazolyl, 2,3-dihydro-1H-benzimidazolyl or 1H-benzotriazolyl group, substituted by an R 3 group and optionally substituted by at least one independently selected R 4 group;

R 3 is selected from a group comprising benzyl, halo-, dihalo- and trihalobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, phenoxy, benzyloxy, halo-, dihalo- and trihalobenzyloxy and benzenesulphonyl;

or R 3 represents trihalomethylbenzyl or trihalomethylbenzyloxy;

or R 3 represents a group of formula

wherein each R 5 is independently selected from halogen, C 1-4 alkyl and C 1-4 alkoxy; and n is 0 to 3;

each R 4 is independently hydroxy, halogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di[C 1-4 alkyl]amino, C 1-4 alkylthio, C 1-4 alkylsulphinyl, C 1-4 alkylsulphonyl, C 1-4 alkylcarbonyl, carboxy, carbamoyl, C 1-4 alkoxycarbonyl, C 1-4 alkanoylamino, N—(C 1-4 alkyl)carbamoyl, N,N-di(C 1-4 alkyl)carbamoyl, cyano, nitro and trifluoromethyl; and

(ii) at least one Raf and/or ras inhibitor.

2 . (canceled)

3 . A method of treating a susceptible cancer in a mammal, comprising: administering to said mammal therapeutically effective amounts of (i) a compound of formula (I)

or a salt, solvate, physiologically functional derivative thereof;

wherein

Y is CR 1 and V is N;

or Y is CR 1 and V is CR 2 ;

R 1 represents a group CH 3 SO 2 CH 2 CH 2 NHCH 2 —Ar—, wherein Ar is selected from phenyl, furan, thiophene, pyrrole and thiazole, each of which may optionally be substituted by one or two halo, C 1-4 alkyl or C 1-4 alkoxy groups;

R 2 is selected from the group comprising hydrogen, halo, hydroxy, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino and di[C 1-4 alkyl]amino;

U represents a phenyl, pyridyl, 3H-imidazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 1H-indazolyl, 2,3-dihydro-1H-indazolyl, 1H-benzimidazolyl, 2,3-dihydro-1H-benzimidazolyl or 1H-benzotriazolyl group, substituted by an R 3 group and optionally substituted by at least one independently selected R 4 group;

R 3 is selected from a group comprising benzyl, halo-, dihalo- and trihalobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, phenoxy, benzyloxy, halo-, dihalo- and trihalobenzyloxy and benzenesulphonyl;

or R 3 represents trihalomethylbenzyl or trihalomethylbenzyloxy;

or R 3 represents a group of formula

wherein each R 5 is independently selected from halogen, C 1-4 alkyl and C 1-4 alkoxy; and n is 0 to 3;

each R 4 is independently hydroxy, halogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di[C 1-4 alkyl]amino, C 1-4 alkylthio, C 1-4 alkylsulphinyl, C 1-4 alkylsulphonyl, C 1-4 alkylcarbonyl, carboxy, carbamoyl, C 1-4 alkoxycarbonyl, C 1-4 alkanoylamino, N—(C 1-4 alkyl)carbamoyl, N,N-di(C 1-4 alkyl)carbamoyl, cyano, nitro and trifluoromethyl; and

(ii) a cRaf-1 inhibitor.

4 . A method of treating a susceptible cancer in a mammal, comprising: administering to said mammal therapeutically effective amounts of (i) a compound of formula (III):

and salt or solvates thereof, wherein R is —Cl or —Br, X is CH, N, or CF, and Z is thiazole or furan; and

(ii) a cRaf-1 inhibitor.

5 . A method of treating a susceptible cancer in a mammal, comprising: administering to said mammal therapeutically effective amounts of (i) a compound of formula (III):

and salts or solvates thereof; and

(ii) a cRaf-1 inhibitor.

6 . A cancer treatment combination, comprising:

therapeutically effective amounts of (i) compound of formula (I)

or a salt, solvate, physiologically functional derivative thereof;

wherein

Y is CR 1 and V is N;

or Y is CR 1 and V is CR 2 ;

R 1 represents a group CH 3 SO 2 CH 2 CH 2 NHCH 2 —Ar—, wherein Ar is selected from phenyl, furan, thiophene, pyrrole and thiazole, each of which may optionally be substituted by one or two halo. C 1-4 alkyl or C 1-4 alkoxy groups;

R 2 is selected from the group comprising hydrogen, halo, hydroxy, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino and di[C 1-4 alkyl]amino;

U represents a phenyl, pyridyl, 3H-imidazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 1H-indazolyl, 2,3-dihydro-1H-indazolyl, 1H-benzimidazolyl, 2,3-dihydro-1H-benzimidazolyl or 1H-benzotriazolyl group, substituted by an R 3 group and optionally substituted by at least one independently selected R 4 group;

R 3 is selected from a group comprising benzyl, halo-, dihalo- and trihalobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, phenoxy, benzyloxy, halo-, dihalo- and trihalobenzyloxy and benzenesulphonyl;

or R 3 represents trihalomethylbenzyl or trihalomethylbenzyloxy;

or R 3 represents a group of formula

wherein each R 5 is independently selected from halogen, C 1-4 alkyl and C 1-4 alkoxy; and n is 0 to 3;

each R 4 is independently hydroxy, halogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di[C 1-4 alkyl]amino, C 1-4 alkylthio, C 1-4 alkylsulphinyl, C 1-4 alkylsulphonyl, C 1-4 alkylcarbonyl, carboxy, carbamoyl, C 1-4 alkoxycarbonyl, C 1-4 alkanoylamino, N-(C 1-4 alkyl)carbamoyl, N,N-di(C 1-4 alkyl)carbamoyl, cyano, nitro and trifluoromethyl; and

(ii) at least one Raf and/or ras inhibitor.

7 . (canceled)

8 . A cancer treatment combination, comprising:

therapeutically effective amounts of (i) a compound of formula (I)

or a salt, solvate, or physiologically functional derivative thereof;

wherein

Y is CR 1 and V is N;

or Y is CR 1 and V is CR 2 ;

R 1 represents a group CH 3 SO 2 CH 2 CH 2 NHCH 2 —Ar—, wherein Ar is selected from phenyl, furan, thiophene, pyrrole and thiazole, each of which may optionally be substituted by one or two halo, C 1-4 alkyl or C 1-4 alkoxy groups;

R 2 is selected from the group comprising hydrogen, halo, hydroxy, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino and di[C 1-4 alkyl]amino;

U represents a phenyl, pyridyl, 3 H -imidazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 1 H -indazolyl, 2,3-dihydro-1 H -indazolyl, 1 H -benzimidazolyl, 2,3-dihydro-1 H -benzimidazolyl or 1 H -benzotriazolyl group, substituted by an R 3 group and optionally substituted by at least one independently selected R 4 group;

R 3 is selected from a group comprising benzyl, halo-, dihalo- and trihalobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, phenoxy, benzyloxy, halo-, dihalo- and trihalobenzyloxy and benzenesulphonyl;

or R 3 represents trihalomethylbenzyl or trihalomethylbenzyloxy;

or R 3 represents a group of formula

wherein each R 5 is independently selected from halogen, C 1-4 alkyl and C 1-4 alkoxy; and n is 0 to 3;

each R 4 is independently hydroxy, halogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di[C 1-4 alkyl]amino, C 1-4 alkylthio, C 1-4 alkylsulphinyl, C 1-4 alkylsulphonyl, C 1-4 alkylcarbonyl, carboxy, carbamoyl, C 1-4 alkoxycarbonyl, C 1-4 alkanoylamino, N-(C 1-4 alkyl)carbamoyl, N,N-di(C 1-4 alkyl)carbamoyl, cyano, nitro and trifluoromethyl; and

(ii) a cRaf-1 inhibitor.

9 . A cancer treatment combination, comprising: therapeutically effective amounts of (i) a compound of formula (II):

and salt or solvates thereof, wherein R is —Cl or —Br, X is CH, N, or CF, and Z is thiazole or furan; and

(ii) a cRaf-1 inhibitor.

10 . A cancer treatment combination, comprising: therapeutically effective amounts of (i) a compound of formula (III):

and salts or solvates thereof; and

(ii) a cRaf-1 inhibitor.

11 - 15 . (canceled)

16 . A method of treating a susceptible cancer in a mammal, comprising: administering to said mammal therapeutically effective amounts of (i) a compound of formula (I)

or a salt, solvate, physiologically functional derivative thereof;

wherein

Y is CR 1 and V is N;

or Y is CR 1 and V is CR 2 ;

R 1 represents a group CH 3 SO 2 CH 2 CH 2 NHCH 2 —Ar—, wherein Ar is selected from phenyl, furan, thiophene, pyrrole and thiazole, each of which may optionally be substituted by one or two halo, C 1-4 alkyl or C 1-4 alkoxy groups;

R 2 is selected from the group comprising hydrogen, halo, hydroxy, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino and di[C 1-4 alkyl]amino;

U represents a phenyl, pyridyl, 3 H -imidazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 1 H -indazolyl, 2,3-dihydro-1 H -indazolyl, 1 H -benzimidazolyl, 2,3-dihydro-1 H -benzimidazolyl or 1 H -benzotriazolyl group, substituted by an R 3 group and optionally substituted by at least one independently selected R 4 group;

R 3 is selected from a group comprising benzyl, halo-, dihalo- and trihalobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, phenoxy, benzyloxy, halo-, dihalo- and trihalobenzyloxy and benzenesulphonyl;

or R 3 represents trihalomethylbenzyl or trihalomethylbenzyloxy;

or R 3 represents a group of formula

wherein each R 5 is independently selected from halogen, C 1-4 alkyl and C 1-4 alkoxy; and n is 0 to 3;

each R 4 is independently hydroxy, halogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di[C 1-4 alkyl]amino, C 1-4 alkylthio, C 1-4 alkylsulphinyl, C 1-4 alkylsulphonyl, C 1-4 alkylcarbonyl, carboxy, carbamoyl, C 1-4 alkoxycarbonyl, C 1-4 alkanoylamino, N—(C 1-4 alkyl)carbamoyl, N,N-di(C 1-4 alkyl)carbamoyl, cyano, nitro and trifluoromethyl; and

(ii) a bRaf inhibitor.

17 . A method of treating a susceptible cancer in a mammal, comprising: administering to said mammal therapeutically effective amounts of (i) a compound of formula (II):

and salt or solvates thereof, wherein R is —Cl or —Br, X is CH, N, or CF, and Z is thiazole or furan; and

(ii) a bRaf inhibitor.

18 . A method of treating a susceptible cancer in a mammal, comprising: administering to said mammal therapeutically effective amounts of (i) a compound of formula (III):

and salts or solvates thereof; and

(ii) a bRaf inhibitor.

19 . (canceled)

20 . A cancer treatment combination, comprising: therapeutically effective amounts of (i) a compound of formula (I)

or a salt, solvate, or physiologically functional derivative thereof;

wherein

Y is CR 1 and V is N;

or Y is CR 1 and V is CR 2 ;

R 1 represents a group CH 3 SO 2 CH 2 CH 2 NHCH 2 —Ar—, wherein Ar is selected from phenyl, furan, thiophene, pyrrole and thiazole, each of which may optionally be substituted by one or two halo, C 1-4 alkyl or C 1-4 alkoxy groups;

R 2 is selected from the group comprising hydrogen, halo, hydroxy, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino and di[C 1-4 alkyl]amino;

U represents a phenyl, pyridyl, 3 H -imidazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 1 H -indazolyl, 2,3-dihydro-1 H -indazolyl, 1 H -benzimidazolyl, 2,3dihydro-1 H -benzimidazolyl or 1 H -benzotriazolyl group, substituted by an R 3 group and optionally substituted by at least one independently selected R 4 group;

R 3 is selected from a group comprising benzyl, halo-, dihalo- and trihalobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, phenoxy, benzyloxy, halo-, dihalo- and trihalobenzyloxy and benzenesulphonyl;

or R 3 represents trihalomethylbenzyl or trihalomethylbenzyloxy;

or R 3 represents a group of formula

wherein each R 5 is independently selected from halogen, C 1-4 alkyl and C 1-4 alkoxy; and n is 0 to 3;

each R 4 is independently hydroxy, halogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di[C 1-4 alkyl]amino, C 1-4 alkylthio, C 1-4 alkylsulphinyl, C 1-4 alkylsulphonyl, C 1-4 alkylcarbonyl, carboxy, carbamoyl, C 1-4 alkoxycarbonyl, C 1-4 alkanoylamino, N—(C 1-4 alkyl)carbamoyl, N,N-di(C 1-4 alkyl)carbamoyl, cyano, nitro and trifluoromethyl; and

(ii) a bRaf inhibitor.

21 . A cancer treatment combination, comprising:

therapeutically effective amounts of (i) a compound of formula (II):

and salt or solvates thereof, wherein R is —Cl or —Br, X is CH, N, or CF, and Z is thiazole or furan; and

(ii) a bRaf inhibitor.

22 . A cancer treatment combination, comprising: therapeutically effective amounts of (i) a compound of formula (III):

and salts or solvates thereof; and

(ii) a bRaf inhibitor.

23 - 24 . (canceled)

25 . The method of claim 1 , wherein the compound of formula (I) is the monohydrate ditosylate salt of

26 . The cancer treatment combination of claim 6 , wherein the compound of formula (I) is the monohydrate ditosylate salt

27 . The method of claim 3 , wherein the compound of formula (I) is the monohydrate ditosylate salt of

28 . The cancer treatment combination of claim 8 , wherein the compound of formula (I) is the monohydrate ditosylate salt

29 . The method of claim 16 , wherein the compound of formula (I) is the monohydrate ditosylate salt of

30 . The method of claim 20 , wherein the compound of formula (I) is the monohydrate ditosylate salt of