Quinazoline compounds

A compound of the formula (I):

• 64
• [wherein:
• ring A is phenyl or a 5-or 6-membered heterocyclic ring which may be saturated, partially saturated or unsaturated and may be aromatic or non-aromatic and which contains 1, 2 or 3 ring heteroatoms selected from O, N and S;
• Z is —O—, —NH— or —S—;
• m is an integer from 0 to 5 inclusive;
• R1 is hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C1-3alkyl, C1-3alkoxy, C1-3alkylthio, or —NR5R6 (wherein R5 and R6, which may be the same or different, are hydrogen or C1-3alkyl);
• R2 is hydrogen, hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, trifluoromethyl, amino or nitro;
• R3 is hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro;
• provided that when ring A is a 5- or 6-membered heterocyclic ring, at least one R3 is either hydroxy or halogeno;
• X1 is —O—, —CH2—, —S—, —SO—, —SO2—, —NR7—, —NR7CO—, —CONR7—, —SO2NR7— or —NR7SO2—, (wherein R7 is hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl);
• R4 is selected from one of the following groups:
• 1) —Y1X2COR8 [wherein Y1— is a C2-5alkylene chain wherein each methylene group (other than that of the α-carbon) is optionally substituted by 1 substituent independently selected from hydroxy, halogeno, amino and C1-4alkanoyloxy, provided that there is at least 1 and no more than 3 substituents on the C2-5alkylene chain;
• X2 is —O— or —NR9— (in which R9 is hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R8 is C1-3alkyl, —NR10R11 or —OR12 (wherein R10, R11 and R12, which may be the same or different, are hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl)];
• 2) —Y2—X3R13 [wherein Y2 is C2-5alkylene, C3-5alkenylene or C3-5alkynylene wherein each methylene group (other than that of the α-carbon) is optionally substituted by 1 substituent independently selected from hydroxy, halogeno, amino and C1-4alkanoyloxy, provided that there is at least 1 substituent and no more than 3 substituents on the alkylene, alkenylene or alkynylene chain;
• X3 is —O—, —S—, —SO—, —SO2—, —OCO—, —NR7CO—, —CONR7—, —SO2NR7—, —NR7SO2— or —NR7— (wherein R7 is as herein defined) and R13 is hydrogen or C1-3alkyl, wherein the C1-3alkyl group may bear one or two substituents selected from oxo, hydroxy, halogeno and C1-4alkoxy;
• 3) —Y1—X6C1-5alkylR14 [wherein Y1 is as herein defined and X6 is —O—, —S—, —SO—, —SO2—, —NR7CO—, —CONR7—, —SO2NR7—, —NR7SO2— or —NR7— (wherein R7 is as herein defined) and R14 is C3-7cycloalkyl or a 3 to 7 membered saturated or partially saturated heterocyclic group containing up to 3 ring heteroatoms selected independently from O, S and N, wherein the carbocyclic or heterocyclic group is optionally substituted by one or two substituents selected from oxo, hydroxy, halogeno, C1-4alkyl, (wherein the C1-4alkyl group is optionally substituted by 1 or 2 substituents selected from hydroxy, cyano, halogeno, amino, nitro, morpholino, C3-5cycloalkyl, piperidin-1-yl and piperazin-1-yl), C2-4alkenyl, C2-4alkynyl, C1-4hydroxyalkyl, C1-4alkoxy, carbamoyl, C1-3alkylcarbamoyl, N,N-di(C1-3alkyl)carbamoyl, C2-4alkanoyl, C1-4alkoxycarbonyl, C1-4alkylthio, C1-4alkylsulphinyl, C1-4alkylsulphonyl, C2-4alkanoylamino, N—C1-3alkyl-C2-4alkanoylamino,
• N—C1-3alkylsulphamoyl, N,N-di-[C1-3alkyl]sulphamoyl, C1-3alkanesulphonylamino and N—C1-3alkyl-C1-3alkanesulphonylamino,
• or R14 is a pyridone group, a phenyl group or a 5 or 6-membered aromatic heterocyclic group containing 1 to 3 ring heteroatoms independently selected from O, N and S, and wherein the pyridone, phenyl or heterocyclic group is optionally substituted by up to 5 substituents selected from halogeno, amino, C1-4alkyl, C1-4alkoxy, C1-4hydroxyalkyl, C1-4aminoalkyl, C1-4alkylamino, C1-4hydroxyalkoxy, carboxy, cyano, C1-4alkylthio, C1-4alkylsulphinyl, C1-4alkylsulphonyl, N—C1-3alkylsulphamoyl, N,N-di-[C1-3alkyl]sulphamoyl, C1-3alkanesulphonylamino, N—C1-3alkyl-C1-3alkanesulphonylamino, —CONR10R11 and —NR10COR11 (wherein R10 and R11 are as herein defined)];
• 4) —Y1—X4C1-5alkylX5R15 [wherein Y1 is as herein defined and X4 and X5 which may be the same or different are each —O—, —S—, —SO—, —SO2—, —NR7CO—, —CONR7—, —SO2NR7—, —NR7SO2— or —NR7— (wherein R7, is as herein defined and R15 is hydrogen or C1-3alkyl)];
• 5) —Y1—O—C1-3alkyl (wherein Y1 is as herein defined) provided that X1 is —O—, —S—, —SO— or —SO2—;
• 6) —Y2—R16 {wherein —Y2— is as herein defined and R16 is a saturated or partially saturated 3 to 7 membered heterocyclic ring containing up to 3 heteroatoms selected from O, S and N [wherein the heterocyclic ring is optionally substituted by up to 3 substitutents selected from oxo, hydroxy, halogeno, C1-4alkyl, C2-4alkenyl, C2-4alkynyl and C3-7cycloalkyl (wherein C1-4alkyl, C2-4alkenyl, C2-4alkynyl and C3-7cycloalkyl are themselves optionally substituted by up to 3 substitutents selected from hydroxy, halogeno, cyano, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, amino, nitro and R14 as herein defined), C1-4alkoxy, carbamoyl, C1-4alkylcarbamoyl, N-N-di(C1-4alkyl)carbamoyl, C2-4alkanoyl, C1-4alkoxycarbonyl, C3-7cycloalkyl, C1-4alkylthio, C1-4alkylsulphinyl, C1-4alkylsulphonyl, C2-4alkanoylamino, N—C1-3alkyl-C2-4alkanoylamino, N—C1-3alkylsulphamoyl, N,N-di-[C1-3alkyl]sulphamoyl, C1-3alkanesulphonylamino and N—C1-3alkyl-C1-3alkanesulphonylamino
• or R16 is a pyridone group, a phenyl group or a 5 or 6-membered aromatic heterocyclic group containing 1 to 3 ring heteroatoms independently selected from O, N and S, and wherein the pyridone, phenyl or heterocyclic group is optionally substituted by up to 5 substituents selected from halogeno, amino, C1-4alkyl, C1-4alkoxy, C1-4hydroxyalkyl, C1-4aminoalkyl, C1-4alkylamino, C1-4hydroxyalkoxy, carboxy, cyano, C1-4alkylthio, C1-4alkylsulphinyl, C1-4alkylsulphonyl, N—C1-3alkylsulphamoyl, N,N-di-[C1-3alkyl]sulphamoyl, C1-3alkanesulphonylamino, N—C1-3alkyl-C1-3alkanesulphonylamino, —CONR10R11 and —NR10COR11 (wherein R10 and R11 (are as herein defined)];
• 7) —Y2—X6—R14 (wherein Y2, X6 and R14 are as herein defined);
• and
• 8) —Y2—NR17R18 [wherein Y2 is as herein defined and R17 and R18 are independently selected from hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl or C1-3alkoxyC1-6alkyl (wherein any alkyl group in R17 or R18 is optionally substituted by up to 2 substituents selected from hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro)];
• 9) —Y3Ra (wherein Y3 is C1-5alkylene, C2-5alkenylene or C2-5alkynylene wherein each methylene group (other than that of the α-carbon) is optionally substituted by 1 substituent independently selected from hydroxy, halogeno, amino and C1-4alkanoyloxy, provided that there are no more than 3 substituents on the alkylene, alkenylene or alkynylene chain;
• and Ra is C3-7cycloalkyl which is substituted by 1 substituent selected from hydroxy, amino and halogeno on the ring carbon lied to Y3 and additionally optionally substituted by up to 3 substitutents selected from oxo, hydroxy, halogeno, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, carbamoyl, C1-4alkylcarbamoyl, N-N-di(C1-4alkyl)carbamoyl, C2-4alkanoyl, C1-4alkoxycarbonyl and C3-7cycloalkyl (wherein C1-4alkyl, C2-4alkenyl, C2-4alkynyl and C3-7cycloalkyl are themselves optionally substituted by up to 3 substitutents selected from hydroxy, halogeno, cyano, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino, nitro and R14 as herein defined)];
• provided that when:
• m is an integer from 1 to 3,
• R1 is methoxy;
• R2 is hydrogen;
• Z is —NH—;
• R3 is halogeno or C1-3alkyl;
• and
• X1 is —O—;
• then
• R4 is not selected from one of the following three groups:
• a) —C2-5alkylR19 (wherein R19 is piperidin-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy);
• b) —C2-5alkenylR19 (wherein R19 is as defined herein);
• c) —C2-5alkynylR19 (wherein R19 is as defined herein);
• wherein any alkylene, alkenylene or alkynylene chain in groups a) to c) above are optionally substituted by one or more substituents selected from hydroxy, halogeno and amino;
• or a salt thereof.