Quinazoline derivatives for the treatment of t cell mediated diseases

• US 20050038050A1
• Filed: 11/20/2002
• Published: 02/17/2005
• Est. Priority Date: 11/23/2001
• Status: Active Grant

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Astrazeneca AB (Astrazeneca PLC)
• Inventors: Moore, Nelly Corine, Oldham, Keith
• Granted Patent: US 7,160,891 B2
• Time in Patent Office: Days
• US Class Current: 514/266.200
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07D 239/94 Nitrogen atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings

Abstract

The invention concerns the use of the quinazoline derivatives of Formula (I) wherein each of Q₁, Z, m, R₁, R₂, R₃ and Q₂ have any of the meanings defined in the description in the manufacture of a medicament for use in the prevention or treatment of T cell mediated diseases or medical conditions in a warm-blooded animal.

Claims

1. The use of a quinazoline derivative of the Formula I

2. The use as claimed in claim 1 of a quinazoline derivative of the Formula I wherein:

m is 0 or m is 1 and the R¹ group is located at the 6- or 7-position and is selected from hydroxy, amino, methyl, ethyl, propyl, methoxy, ethoxy, propoxy, methylamino, ethylamino, dimethylamino, diethylamino, acetamido, propionamido, benzyloxy, 2-imidazol-1-ylethoxy, 2-(1,2,4-triazol-1-yl)ethoxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, pyrrolidin-3-yloxy, pyrrolidin-2-ylmethoxy, 2-pyrrolidin-2-ylethoxy, 3-pyrrolidin-2-ylpropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)ethoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, piperidin-3-yloxy, piperidin-4-yloxy, piperidin-3-ylmethoxy, 2-piperidin-3-ylethoxy, piperidin-4-ylmethoxy, 2-piperidin-4-ylethoxy, 2-homopiperidin-1-ylethoxy, 3-homopiperidin-1-ylpropoxy, 2-piperazin-1-ylethoxy, 3-piperazin-1-ylpropoxy, 2-homopiperazin-1-ylethoxy and 3-homopiperazin-1-ylpropoxy,

and wherein adjacent carbon atoms in any (2-6C)alkylene chain within a 10 substituent are optionally separated by the insertion into the chain of a group selected from O, NH, CH═

CH and C≡

C,

and wherein any CH₂ or CH₃ group within a R¹ substituent optionally bears on each said CH₂ or CH₃ group a substituent selected from hydroxy, amino, methoxy, methylsulphonyl, methylamino and dimethylamino,

and wherein any phenyl or heterocyclyl group within a substituent on R¹ optionally bears 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, trifluoromethyl, hydroxy, amino, methyl, ethyl and methoxy,

and wherein any heterocyclyl group within a substituent on R¹ optionally bears 1 or 2 oxo substituents;

the Q¹-Z- group is selected from propoxy, isopropoxy, 2-hydroxyethoxy, 3-hydroxypropoxy, 2-methoxyethoxy, 3-methoxypropoxy, cyclopentyloxy, cyclohexyloxy, phenoxy, benzyloxy, tetrahydrofuran-3-yloxy, tetrahydropyran-3-yloxy, tetrahydropyran-4-yloxy, 2-imidazol-1-ylethoxy, 2-(1,2,4-triazol-1-yl)ethoxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, pyrrolidin-3-yloxy, pyrrolidin-2-ylmethoxy, 2-pyrrolidin-2-ylethoxy, 3-pyrrolidin-2-ylpropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)ethoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, piperidin-3-yloxy, piperidin-4-yloxy, piperidin-3-ylmethoxy, 2-piperidin-3-ylethoxy, piperidin-4-ylmethoxy, 2-piperidin-4ylethoxy, 2-homopiperidin-1-ylethoxy, 3-homopiperidin-1-ylpropoxy, homopiperidin-3-yloxy, homopiperidin-4-yloxy, homopiperidin-3-ylmethoxy, 2-piperazin-1-ylethoxy, 3-piperazin-1-ylpropoxy, 2-homopiperazin-1-ylethoxy or 3-homopiperazin-1-ylpropoxy,

and wherein any CH₂ or CH₃ group within the Q¹-Z- group optionally bears on each said CH₂ or CH₃ group a substituent selected from hydroxy, amino, methoxy, methylsulphonyl, methylamino and dimethylamino,

and wherein any phenyl or heterocyclyl group within the Q¹-Z- group optionally bears 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, trifluoromethyl, hydroxy, amino, methyl, ethyl and methoxy,

and wherein any heterocyclyl group within the Q¹-Z- group optionally bears 1 or 2 oxo substituents;

each of R² and R³ is hydrogen; and

Q² is an aryl group of formula Ia

wherein G¹ is selected from fluoro, chloro, bromo, iodo, trifluoromethyl, cyano, methyl, ethyl, vinyl, allyl, isopropenyl, ethynyl, methoxy and ethoxy, and each of G², G³, G⁴ and G⁵, which may be the same-or different, is selected from hydrogen, fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl, ethyl, vinyl, allyl, isopropenyl, ethynyl, methoxy and ethoxy,

or G¹ and G² together form a group of formula;

—

—

CH═

CH—

CH═

CH—

, —

O—

CH═

CH—

or —

O—

CH₂—

O—

, and the 9- or 10-membered bicyclic heteroaryl or heterocyclic ring so formed optionally bears on the heteroaryl or heterocyclic portion of the bicyclic ring 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl, ethyl, methoxy and ethoxy, and any bicyclic heterocyclic ring so formed optionally bears 1 or 2 oxo or thioxo groups, and each of G³, G⁴ and G⁵, which may be the same or different, is selected from hydrogen, fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl, ethyl, methoxy and ethoxy;

or a pharmaceutically-acceptable acid-addition salt thereof.

3. The use as claimed in claim 1 of a quinazoline derivative of the Formula I wherein:

m is 1 and the R¹ group is located at the 7-position and is selected from hydroxy, methoxy, benzyloxy, 3-morpholinopropoxy, 2-hydroxy-3-morpholinopropoxy, 3-(4-methylpiperazin-1-yl)propoxy, 2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy, 2-methoxyethoxy and 2-(2-methoxyethoxy)ethoxy;

the Q¹-Z- group is selected from isopropoxy, 2-methoxyethoxy, cyclohexyloxy, tetrahydrofuran-3-yloxy, tetrahydropyran-4-yloxy, 2-imidazol-1-ylethoxy, 2-(1,2,4-triazol-1-yl)ethoxy, 3-pyrrolidin-1-ylpropoxy, N-methylpyrrolidin-3-yloxy, 3-morpholinopropoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, N-methylpiperidin-4-yloxy, piperidin-4-ylmethoxy, N-methylpiperidin-4-ylmethoxy and 3-(4-methylpiperazin-1-yl)propoxy,

each of R² and R³ is hydrogen; and

Q² is an aryl group of formula Ia

wherein G¹ is selected from fluoro, chloro, bromo and iodo, each of G³ and G⁴, which may be the same or different, is selected from hydrogen, chloro and methoxy, and each of G² and G⁵ is hydrogen,

or G¹ and G² together form a group of formula;

—

—

CH═

CH—

CH═

C(Cl)—

, —

O—

CH═

C(Cl)—

or —

O—

CH₂—

O—

, and each of G³, G⁴ and G⁵ is hydrogen;

or a pharmaceutically-acceptable acid-addition salt thereof.

4. The use as claimed in claim 1 of a quinazoline derivative of the Formula I wherein:

m is 0 or m is 1 and the R¹ group is located at the 6- or 7-position and is selected from hydroxy, amino, methyl, ethyl, propyl, methoxy, ethoxy, propoxy, methylamino, ethylamino, dimethylamino, diethylamino, acetamido, propionamido, benzyloxy, 2-imidazol-1-ylethoxy, 2-(1,2,4-triazol-1-yl)ethoxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, pyrrolidin-3-yloxy, pyrrolidin-2-ylmethoxy, 2-pyrrolidin-2-ylethoxy, 3-pyrrolidin-2-ylpropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(1,1-dioxotetrahydro-4H-1,4thiazin-4-yl)ethoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, piperidin-3-yloxy, piperidin-4-yloxy, piperidin-3-ylmethoxy, 2-piperidin-3-ylethoxy, piperidin-4-ylmethoxy, 2-piperidin-4-ylethoxy, 2-homopiperidin-1-ylethoxy, 3-homopiperidin-1-ylpropoxy, 2-piperazin-1-ylethoxy, 3-piperazin-1-ylpropoxy, 2-homopiperazin-1-ylethoxy and 3-homopiperazin-1-ylpropoxy,

and wherein adjacent carbon atoms in any (2-6C)alkylene chain within a R¹ substituent are optionally separated by the insertion into the chain of a group selected from O, NH, CH═

CH and C≡

C,

and wherein any CH₂ or CH₃ group within a R¹ substituent optionally bears on each said CH₂ or CH₃ group a substituent selected from hydroxy, amino, methoxy, methylsulphonyl, methylamino and dimethylamino,

and wherein any phenyl or heterocyclyl group within a substituent on R¹ optionally bears 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, trifluoromethyl, hydroxy, amino, methyl, ethyl and methoxy,

and wherein any heterocyclyl group within a substituent on R¹ optionally bears 1 or 2oxo substituents;

the Q¹-Z- group is selected from phenoxy, benzyloxy, tetrahydrofuran-3-yloxy, tetrahydropyran-3-yloxy, tetrahydropyran-4-yloxy, 2-imidazol-1-ylethoxy, 2-(1,2,4-triazol-1-yl)ethoxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, pyrrolidin-3-yloxy, pyrrolidin-2-ylmethoxy, 2-pyrrolidin-2-ylethoxy, 3-pyrrolidin-2-ylpropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)ethoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, piperidin-3-yloxy, piperidin-4-yloxy, piperidin-3-ylmethoxy, 2-piperidin-3-ylethoxy, piperidin-4-ylmethoxy, 2-piperidin-4-ylethoxy, 2-homopiperidin-1-ylethoxy, 3-homopiperidin-1-ylpropoxy, homopiperidin-3-yloxy, homopiperidin-4-yloxy, homopiperidin-3-ylmethoxy, 2-piperazin-1-ylethoxy, 3-piperazin-1-ylpropoxy, 2-homopiperazin-1-ylethoxy or 3-homopiperazin-1-ylpropoxy,

and wherein any CH₂ or CH₃ group within the Q¹-Z- group optionally bears on each said CH₂ or CH₃ group a substituent selected from hydroxy, amino, methoxy, methylsulphonyl, methylamino and dimethylamino,

and wherein any phenyl or heterocyclyl group within the Q¹-Z- group optionally bears 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, trifluoromethyl, hydroxy, amino, methyl, ethyl and methoxy,

and wherein any heterocyclyl group within the Q¹-Z- group optionally bears 1 or 2 oxo substituents;

each of R² and R³ is hydrogen; and

Q² is an aryl group of formula Ia

wherein G¹ is selected from fluoro, chloro, bromo, iodo, trifluoromethyl, cyano, methyl, ethyl, vinyl, allyl, isopropenyl, ethynyl, methoxy and ethoxy, and each of G², G³, G⁴ and G⁵, which may be the same or different, is selected from hydrogen, fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl, ethyl, vinyl, allyl, isopropenyl, ethynyl, methoxy and ethoxy,

or G¹ and G² together form a group of formula;

—

—

CH═

CH—

CH═

CH—

, —

O—

CH═

CH—

or —

O—

CH₂—

O—

, and the 9- or 10-membered bicyclic heteroaryl or heterocyclic ring so formed optionally bears on the heteroaryl or heterocyclic portion of the bicyclic ring 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl, ethyl, methoxy and ethoxy, and any bicyclic heterocyclic ring so formed optionally bears 1 or 2 oxo or thioxo groups, and each of G³, G⁴ and G⁵, which may be the same or different, is selected from hydrogen, fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl, ethyl, methoxy and ethoxy,

or a pharmaceutically-acceptable acid-addition salt thereof.

5. The use as claimed in claim 1 of a quinazoline derivative of the Formula I wherein:

m is 1 and the R¹ group is located at the 7-position and is selected from hydroxy, methoxy, ethoxy, propoxy, benzyloxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)ethoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, 2-(4-methylpiperazin-1-yl)ethoxy, 3-(4-methylpiperazin-1-yl)propoxy, 2-hydroxyethoxy, 3-hydroxypropoxy, 2-methoxyethoxy, 3-methoxypropoxy, 2-methylsulphonylethoxy, 3-methylsulphonylpropoxy and 2-(2-methoxyethoxy)ethoxy;

and wherein any CH₂ group within a R¹ substituent that is attached to two carbon atoms optionally bears a hydroxy group on said CH₂ group;

the Q¹-Z- group is selected from tetrahydrofuran-3-yloxy, tetrahydropyran-4-yloxy, 2-imidazol-1-ylethoxy, 2-(1,2,4-triazol-1-yl)ethoxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, pyrrolidin-3-yloxy, N-methylpyrrolidin-3-yloxy, pyrrolidin-2-ylmethoxy, 2-pyrrolidin-2-ylethoxy, 3-pyrrolidin-2-ylpropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)ethoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, piperidin-3-yloxy, N-methylpiperidin-3-yloxy, piperidinyloxy, N-methylpiperidin-4-yloxy, piperidin-3-ylmethoxy, N-methylpiperidin-3-ylmethoxy, piperidin-4-ylmethoxy, N-methylpiperidin-4-ylmethoxy, 2-(4-methylpiperazin-1-yl)ethoxy and 3-(4-methylpiperazin-1-yl)propoxy,

and wherein any CH₂ group within the Q¹-Z- group that is attached to two carbon atoms optionally bears a hydroxy group on said CH₂ group;

and wherein any heterocyclyl group within the Q¹-Z- group optionally bears 1 or 2 oxo substituents;

each of R² and R³ is hydrogen; and

Q² is an aryl group of formula Ia

wherein G¹ is selected from fluoro, chloro, bromo, iodo, trifluoromethyl, cyano, methyl, ethyl, vinyl, isopropenyl and ethynyl, each of G³ and G⁴, which may be the same or different, is selected from hydrogen, fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl, ethyl, vinyl, allyl, isopropenyl, ethynyl, methoxy and ethoxy, and each of G² and G⁵ is hydrogen, or G¹ and G² together form a group of formula;

—

—

CH═

CH—

CH═

CH—

, —

O—

CH═

CH—

or —

O—

CH₂—

O—

, and the 9- or 10-membered bicyclic heteroaryl or heterocyclic ring so formed optionally bears on the heteroaryl or heterocyclic portion of the bicyclic ring 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl and methoxy, and each of G³, G⁴ and G⁵, which may be the same or different, is selected from hydrogen, fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl and methoxy;

or a pharmaceutically-acceptable acid-addition salt thereof.

6. The use as claimed in claim 1 of a quinazoline derivative of the Formula I wherein:

m is 1 and the R¹ group is located at the 7-position and is selected from hydroxy, methoxy, benzyloxy, 3-morpholinopropoxy, 2-hydroxy-3-morpholinopropoxy, 3-(4-methylpiperazin-1-yl)propoxy, 2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy, 2-methoxyethoxy and 2-(2-methoxyethoxy)ethoxy,

the Q¹-Z- group is selected from tetrahydrofuran-3-yloxy, tetrahydropyran-4-yloxy, 2-imidazol-1-ylethoxy, 2-(1,2,4-triazol-1-yl)ethoxy, 3-pyrrolidin-1-ylpropoxy, N-methylpyrrolidin-3-yloxy, 3-morpholinopropoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, N-methylpiperidin-4-yloxy, piperidin-4-ylmethoxy, N-methylpiperidin-4-ylmethoxy and 3-(4-methylpiperazin-1-yl)propoxy,

each of R² and R³ is hydrogen; and

Q² is an aryl group of formula Ia

wherein G¹ is selected from fluoro, chloro, bromo and iodo, each of G³ and G⁴, which may be the same or different, is selected from hydrogen, chloro and methoxy, and each of G² and G⁵ is hydrogen,

or G¹ and G² together form a group of formula;

—

—

CH═

CH—

CH═

C(Cl)—

, —

O—

CH═

C(Cl)—

or —

O—

CH₂—

O—

, and each of G³, G⁴ and G⁵ is hydrogen;

or a pharmaceutically-acceptable acid-addition salt thereof.

7. The use as claimed in claim 1 of a quinazoline derivative of the Formula I wherein:

m is 1 and the R¹ group is located at the 7-position and is selected from hydroxy, methoxy, ethoxy, propoxy, isopropoxy, isobutoxy, 2-fluoroethoxy, 2,2,2-trifluoroethoxy, benzyloxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)ethoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, 2-piperidin-4-ylethoxy, 2-(N-methylpiperidin-4-yl)ethoxy, 2-homopiperidin-1-ylethoxy, 3-homopiperidin-1-ylpropoxy, 2-piperazin-1-ylethoxy, 3-piperazin-1-ylpropoxy, 2-(4-methylpiperazin-1-yl)ethoxy, 3-(4-methylpiperazin-1-yl)propoxy, 3-(4-cyanomethylpiperazin-1-yl)propoxy, 2-[(2S)-2-carbamoylpyrrolidin-1-yl]ethoxy, 2-[(2S)-2-(N-methylcarbamoyl)pyrrolidin-1-yl]ethoxy, 2-[(2S)-2-(N,N-dimethylcarbamoyl)pyrrolidin-1-yl]ethoxy, 2-tetrahydropyran-4-ylethoxy, 2-hydroxyethoxy, 3-hydroxypropoxy, 2-methoxyethoxy, 3-methoxypropoxy, 2-methylsulphonylethoxy, 3-methylsulphonylpropoxy, 2-(2-methoxyethoxy)ethoxy, piperidin-4-ylmethoxy, N-methylpiperidin-4-ylmethoxy, 2-(4-pyridyloxy)ethoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy and 3-cyanopyrid-4-ylmethoxy;

and wherein any CH₂ group within a R¹ substituent that is attached to two carbon atoms optionally bears a hydroxy group on said CH₂ group;

the Q¹-Z- group is selected from tetrahydrofuran-3-yloxy, tetrahydropyranyloxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, pyrrolidin-3-yloxy, N-methylpyrrolidin-3-yloxy, pyrrolidin-2-ylmethoxy, 2-pyrrolidin-2-ylethoxy, 3-pyrrolidin-2-ylpropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)ethoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, 3-piperidinyloxy, N-methylpiperidin-3-yloxy, 4-piperidinyloxy, N-methylpiperidin-4-yloxy, piperidin-3-ylmethoxy, N-methylpiperidin-3-ylmethoxy, piperidin-4-ylmethoxy, N-methylpiperidin-4-ylmethoxy, 2-(4-methylpiperazin-1-yl)ethoxy, 3-(4-methylpiperazin-1-yl)propoxy, cyclobutyloxy, cyclopentyloxy and cyclohexyloxy,

and wherein any CH₂ group within the Q¹-Z- group that is attached to two carbon atoms optionally bears a hydroxy group on said CH₂ group;

and wherein any heterocyclyl group within the Q¹-Z- group optionally bears 1 or 2 oxo substituents;

each of R² and R³ is hydrogen; and

Q² is an aryl group of formula Ia

wherein G¹ is selected from fluoro, chloro, bromo, iodo, trifluoromethyl, cyano, methyl, ethyl, vinyl, isopropenyl, ethynyl, methoxy and pyrrolidin-lyl, G² is hydrogen, each of G³ and G⁴, which may be the same or different, is selected from hydrogen, fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl, ethyl, vinyl, allyl, isopropenyl, ethynyl, methoxy and ethoxy, and G⁵ is hydrogen or methoxy,

or G¹ and G² together form a group of formula;

—

—

CH—

CH—

CH═

CH—

, —

O—

CH═

CH—

or —

O—

CH₂—

O—

, and the 9- or 10-membered bicyclic heteroaryl or heterocyclic ring so formed optionally bears on the heteroaryl or heterocyclic portion of the bicyclic ring 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl and methoxy, and each of G³, G⁴ and G⁵, which may be the same or different, is selected from hydrogen, fluoro, chloro, bromo, trifluoromethyl, cyano, hydroxy, methyl and methoxy,

or a pharmaceutically-acceptable acid-addition salt thereof.

8. The use as claimed in claim 1 of a quinazoline derivative of the Formula I wherein:

m is 1 and the R¹ group is located at the 7-position and is selected from hydroxy, methoxy, benzyloxy, 3-morpholinopropoxy, 2-hydroxy-3-morpholinopropoxy, 3-(4-methylpiperazin-1-yl)propoxy, 2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy, 2-methoxyethoxy and 2-(2-methoxyethoxy)ethoxy;

the Q¹-Z- group is selected from tetrahydrofuran-3-yloxy, tetrahydropyran-4-yloxy, 3-pyrrolidin-1-ylpropoxy, N-methylpyrrolidin-3-yloxy, 3-morpholinopropoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, N-methylpiperidin-4-yloxy, piperidin-4ylmethoxy, N-methylpiperidin-4-ylmethoxy and 3-(4methylpiperazin-1-yl)propoxy,

each of R² and R³ is hydrogen; and

Q² is an aryl group of formula Ia

wherein G¹ is selected from fluoro, chloro, bromo and iodo, each of G³ and G⁴, which may be the same or different, is selected from hydrogen, chloro and methoxy, and each of G² and G⁵ is hydrogen,

or G¹ and G² together form a group of formula;

—

—

CH═

CH—

CH═

C(Cl)—

, —

O—

CH═

C(Cl)—

or —

O—

CH₂—

O—

, and each of G³, G⁴ and G⁵ is hydrogen;

or a pharmaceutically-acceptable acid-addition salt thereof.

9. The use as claimed in claim 1 of a quinazoline derivative of the Formula I wherein:

m is 1 and the R¹ group is located at the 7-position and is selected from methoxy, benzyloxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(4-methylpiperazin-1-yl)ethoxy, 3-(4methylpiperazin-1-yl)propoxy, 2-[(2S)-2-M-methylcarbamoyl)pyrrolidin-1-yl]ethoxy, 2-[(2S)-2-(,N-dimethylcarbamoyl)pyrrolidin-1-yl]ethoxy, 3-methylsulphonylpropoxy, 2-(4-pyridyloxy)ethoxy, 2-pyridylmethoxy, 3-pyridylmethoxy and 4-pyridylmethoxy,

the Q¹-Z- group is selected from tetrahydropyran-4-yloxy, 3-pyrrolidin-1-ylpropoxy, N-methylpyrrolidin-3-yloxy, 3-morpholinopropoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, 4-piperidinyloxy, N-methylpiperidin-4-yloxy, piperidin-4-ylmethoxy, N-methylpiperidin-4-ylmethoxy, 3-(4-methylpiperazin-1-yl)propoxy, cyclopentyloxy and cyclohexyloxy;

each of R² and R³ is hydrogen; and

Q² is an aryl group of formula Ia

wherein G¹ is selected from chloro, bromo, trifluoromethyl, methyl, methoxy and pyrrolidin-1-yl, G² is hydrogen, G³ is selected from hydrogen and chloro, G⁴ is methoxy, and G⁵ is hydrogen,

or G¹ and G² together form a group of formula;

—

—

CH═

CH—

CH═

C(Cl)—

, —

O—

CH═

C(Cl)—

or —

O—

CH₂—

O—

, each of G³ and G⁴ is hydrogen, and G⁵ is hydrogen or chloro;

or a pharmaceutically-acceptable acid-addition salt thereof.

10. The use as claimed in claim 1 of a quinazoline derivative of the Formula I wherein:

m is 1 and the R¹ group is located at the 7-position and is selected from methoxy, ethoxy, propoxy, isopropoxy, isobutoxy, 2-fluoroethoxy, 2,2,2-trifluoroethoxy, benzyloxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, 2-piperidin-4-ylethoxy, 2-(N-methylpiperidin-4-yl)ethoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)ethoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-homopiperidin-1-ylethoxy, 3-homopiperidin-1-ylpropoxy, 2-piperazin-1-ylethoxy, 3-piperazin-1-ylpropoxy, 2-(4-methylpiperazin-1-yl)ethoxy, 3-(4-methylpiperazin-1-yl)propoxy, 3-(4-cyanomethylpiperazin-1-yl)propoxy, 2-[(2S)-2-carbamoylpyrrolidin-1-yl]ethoxy, 2-[(2S)-2-(N-methylcarbamoyl)pyrrolidin-1-yl]ethoxy, 2-[(2S)-2-(N,N-dimethylcarbamoyl)pyrrolidin-1-yl]ethoxy, 3-methylsulphonylpropoxy, piperidin-4-ylmethoxy, N-methylpiperidin-4-ylmethoxy, 2-(4-pyridyloxy)ethoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy and 2-cyanopyrid-4-ylmethoxy,

and wherein any CH₂ group within a R¹ substituent that is attached to two carbon atoms optionally bears a hydroxy group on said CH₂ group;

the Q¹-Z- group is selected from tetrahydropyran-4-yloxy, 3-pyrrolidin-1-ylpropoxy, N-methylpyrrolidin-3-yloxy, 3-morpholinopropoxy, 3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy, 2-piperidinoethoxy, 4-piperidinyloxy, N-methylpiperidin-4-yloxy, piperidin-4-ylmethoxy, N-methylpiperidin-4-ylmethoxy, 3-(4-methylpiperazin-1-yl)propoxy, cyclopentyloxy and cyclohexyloxy;

each of R¹ and R³ is hydrogen; and

Q² is an aryl group of formula Ia

wherein G¹ is selected from chloro, bromo, trifluoromethyl, methyl, methoxy and pyrrolidin-1-yl, G² is hydrogen, G³ is selected from hydrogen and chloro, G⁴ is methoxy, and G⁵ is hydrogen,

or G¹ and G² together form a group of formula;

—

—

O—

CH═

CH—

, —

O—

CH═

C(Cl)—

or —

O—

CH₂—

O—

, each of G³ and G⁴ is hydrogen, and G⁵ is hydrogen or chloro;

or a pharmaceutically-acceptable acid-addition salt thereof.

11. The use as claimed in claim 1 of a quinazoline derivative of the Formula I wherein:

m is 1 and the R¹ group is located at the 7-position and is selected from methoxy, benzyloxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(4methylpiperazin-1-yl)ethoxy, 3-(4-methylpiperazin-1-yl)propoxy, 2-[(2S)-2-(N-methylcarbamoyl)pyrrolidin-1-yl]ethoxy, 2-[(2S)-2-(N,N-dimethylcarbamoyl)pyrrolidin-1-yl]ethoxy, 3-methylsulphonylpropoxy, 2-(4-pyridyloxy)ethoxy, 2-pyridylmethoxy, 3-pyridylmethoxy and 4-pyridylmethoxy;

the Q¹-Z- group is selected from tetrahydropyran-4-yloxy, 4-piperidinyloxy, N-methylpiperidin-4-yloxy, cyclopentyloxy and cyclohexyloxy,

each of R² and R³ is hydrogen; and

Q² is an aryl group of formula Ia

wherein G¹ and G² together form a group of formula;

—

—

O—

CH₂—

O—

, each of G³ and G⁴ is hydrogen, and G⁵ is chloro;

or a pharmaceutically-acceptable acid-addition salt thereof.

12. The use as claimed in claim 1 of a quinazoline derivative of the Formula I wherein:

m is 1 and the R¹ group is located at the 7-position and is selected from methoxy, ethoxy, propoxy, isopropoxy, isobutoxy, 2-fluoroethoxy, 2,2,2-trifluoroethoxy, benzyloxy, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, 3-(4-hydroxypiperidin-1-yl)propoxy, 2-piperidin-4-ylethoxy, 2-(N-methylpiperidin-4-yl)ethoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-piperazin-1-ylethoxy, 3-piperazin-1-ylpropoxy, 2-(4-methylpiperazin-1-yl)ethoxy, 3-(4-methylpiperazin-1-yl)propoxy, 3-(4cyanomethylpiperazin-1-yl)propoxy, 2-[(2S)-2-carbamoylpyrrolidin-1-yl]ethoxy, 2-[(2S)-2-(h-methylcarbamoyl)pyrrolidin-1-yl]ethoxy, 2-[(2S)-2-(N-dimethylcarbamoyl)pyrrolidin-1-yl]ethoxy, 3-methylsulphonylpropoxy, piperidin-4-ylmethoxy, N-methylpiperidin-4-ylmethoxy, 2-(4-pyridyloxy)ethoxy, 2-pyridylmethoxy, 3-pyridylmethoxy and 4-pyridylmethoxy;

the Q¹-Z- group is selected from tetrahydropyran-4-yloxy, 4-piperidinyloxy, N-methylpiperidin-4-yloxy, piperidin-4-ylmethoxy, N-methylpiperidin-4-ylmethoxy, cyclopentyloxy and cyclohexyloxy;

each of R² and R³ is hydrogen; and

Q² is an aryl group of formula Ia

wherein G¹ and G² together form a group of formula;

—

—

O—

CH₂—

O—

, each of G³ and G⁴ is hydrogen, and G⁵ is chloro;

or a pharmaceutically-acceptable acid-addition salt thereof.

13. The use as claimed in claim 1 of a quinazoline derivative of the Formula I selected from:

—

4-(2-chloro-5-methoxyanilino)-5,7-di-(3-morpholinopropoxy)quinazoline,

4-(2-bromo-5-methoxyanilino)-7-methoxy-5-(N-methylpiperidin-4-yloxy)quinazoline,

4-(2-chloro-5-methoxyanilino)-7-methoxy-5-1-methylpiperidin-4-yloxy)quinazoline,

4-(2-chloro-5-methoxyanilino)-7-[3-(4-methylpiperazin-1-yl)propoxy]-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-chloro-5-methoxyanilino)-7-(3-morpholinopropoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-chloro-5-methoxyanilino)-7-[2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy]-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-chloro-5-methoxyanilino)-7-(2-hydroxy-3-morpholinopropoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-chloro-5-methoxyanilino)-7-[3-(4-methylpiperazin-1-yl)propoxy]-5-tetrahydrofuran-3-yloxyquinazoline,

4-(2-chloro-5-methoxyanilino)-7-(3-morpholinopropoxy)-5-tetrahydrofuran-3-yloxyquinazoline,

4-(5-chloronaphth-1-ylamino)-7-methoxy-5-(N-methylpiperidin-4-yloxy)quinazoline,

4-(3-chlorobenzofuran-7-ylamino)-7-methoxy-5-(N-methylpiperidinyloxy)quinazoline,

7-benzyloxy-4-(2-bromo-5-methoxyanilino)-5-piperidin-4-yloxyquinazoline,

4-(2-bromo-5-methoxyanilino)-7-(3-methylsulphonylpropoxy)-5-piperidin-4-yloxyquinazoline,

4-(2-bromo-5-methoxyanilino)-7-methoxy-5-piperidin-4-ylmethoxyquinazoline,

4-(2,4-dichloro-5-methoxyanilino)-7-methoxy-5-(N-methylpiperidin-4-yloxy)quinazoline,

4-(2,5-dimethoxyanilino)-7-methoxy-5-(N-methylpiperidin-4-yloxy)quinazoline,

4-(2,4-dichloro-5-methoxyanilino)-7-(2-pyrrolidin-1-ylethoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(2,4-dichloro-5-methoxyanilino)-7-(2-piperidinoethoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(2,4-dichloro-5-methoxyanilino)-7-(2-morpholinoethoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(2,4-dichloro-5-methoxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-bromo-5-methoxyanilino)-7-(2-pyrrolidin-1-ylethoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-bromo-5-methoxyanilino)-7-(2-piperidinoethoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-bromo-5-methoxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4yloxyquinazoline,

4-(2-bromo-5-methoxyanilino)-7-(4-pyridyloxyethoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-bromo-5-methoxyanilino)-7-{2-[(2S)-2-(N,N-dimethylcarbamoyl)pyrrolidin-1-yl] ethoxy}-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-bromo-5-methoxyanilino)-7-{2-[(2S)-2-(N-methylcarbamoyl)pyrrolidin-1-yl]ethoxy}-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-bromo-5-methoxyanilino)-7-(4-pyridylmethoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(5-methoxy-2-pyrrolidin-1-ylanilino)-7-[3-(4-methylpiperazin-1-yl)propoxy]-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-bromo-5-methoxyanilino)-5-cyclopentyloxy-7-(2-pyrrolidin-1-ylethoxy)quinazoline,

4-(2-chloro-5-methoxyanilino)-5-isopropoxy-7-(3-morpholinopropoxy)quinazoline,

4-(2-chloro-5-methoxyanilino)-5-isopropoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-5-cyclopentyloxy-7-(2-pyrrolidin-1-ylethoxy)quinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-5-piperidin-4-yloxyquinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-7-methoxy-5-piperidin-4-yloxyquinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-7-methoxy-5-(N-methylpiperidin-4-yloxy)quinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-7-methoxy-5-piperidin-4-ylmethoxyquinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-7-(2-pyrrolidin-1-ylethoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-7-(3-pyrrolidin-1-ylpropoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-7-[3-(4-methylpiperazin-1-yl)propoxy]-5-tetrahydropyran-4-yloxyquinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4-yloxyquinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-7-(2-piperidinoethoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-pyridyloxy)ethoxy]-5-tetrahydropyran-4-yloxyquinazoline,

4-(6-chloro-2,3-methylenedioxyanilino)-7-piperidin-4-ylmethoxy-5-tetrahydropyran-4-yloxyquinazoline and

4-(6-chloro-2,3-methylenedioxyanilino)-7-(N-methylpiperidin-4-ylmethoxy)-5-tetrahydropyran-4-yloxyquinazoline;

or a pharmaceutically-acceptable acid-addition salt thereof.

14. The use as claimed in claim 1 of a quinazoline derivative of the Formula I selected from:

—

4-(2-chloro-5-methoxyanilino)-7-[3-(4-methylpiperazin-1-yl)propoxy]-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-chloro-5-methoxyanilino)-7-(3-morpholinopropoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(2,4-dichloro-5-methoxyanilino)-7-(2-pyrrolidin-1-ylethoxy)-5-tetrahydropyran-4-yloxyquinazoline,

4-(2-chloro-5-methoxyanilino)-5-isopropoxy-7-(3-morpholinopropoxy)quinazoline and

4-(6-chloro-2,3-methylenedioxyanilino)-7-(2-pyrrolidin-1-ylethoxy)-5-tetrahydropyran-4-yloxyquinazoline,

or a pharmaceutically-acceptable acid-addition salt thereof.