Aniline derivatives

• US 5,821,246 A
• Filed: 05/21/1997
• Issued: 10/13/1998
• Est. Priority Date: 11/12/1994
• Status: Expired due to Term

• Current Assignee: Astrazeneca UK Limited (Astrazeneca PLC)
• Original Assignee: Zeneca Incorporated (Astrazeneca PLC)
• Inventors: Thomas, Andrew Peter, Brown, Dearg Sutherland, Morris, Jeffrey James
• Primary Examiner(s): Grumbling, Matthew V.
• Application Number:
  US08/836,362
• Time in Patent Office: 510 Days
• Field of Search: 544/293, 544/284, 514/259, 514/253
• US Class Current: 514/252.17
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 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 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

The invention concerns aniline derivatives of formula I ##STR1## wherein m is 1, 2 or 3, n is 0, 1, 2 or 3, Q is phenyl or naphthyl or a 5- or 6-membered heteroaryl moiety containing 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulfur, and X, R¹ and R² are defined in the claims; or pharmaceutical compositions containing them, and the methods of using the compounds as tyrosine kinase inhibitors and for the treatment of proliferative diseases such as cancer.

Claims

1. An aniline derivative of the formula I

wherein:

m is 1, 2 or 3;

each R¹ is independently hydroxy, amino, hydroxyamino, ureido, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy, (2-4C)alkanoyloxy, (2-4C)alkenyloxy, (2-4C)alkynyloxy, (1-3C)alkylenedioxy, (1-4C)alkylamino, di- (1-4C)alkyl!amino, pyrrolidin-1-yl, piperidino, morpholino, piperazin-1-yl, 4-(1-4C)alkylpiperazin-1-yl, (1-4C)alkylthio, halogeno-(2-4C)alkoxy, hydroxy-(2-4C)alkoxy, (1-4C)alkoxy-(2-4C)alkoxy, amino-(2-4C)alkoxy, (1-4C)alkylamino-(2-4C)alkoxy, di- (1-4C)alkyl!amino-(2-4C)alkoxy, pyrrolidin-1-yl-(2-4C)alkoxy, piperidino-(2-4C)alkoxy, morpholino-(2-4C)alkoxy, piperazin-1-yl-(2-4C)alkoxy, 4-(1-4C)alkylpiperazin-1-yl-(2-4C)alkoxy, hydroxy-(2-4C)alkylamino-(2-4C)alkoxy, di- hydroxy-(2-4C)alkyl!amino-(2-4C)alkoxy, (1-4C)alkoxy-(2-4C)alkylamino-(2-4C)alkoxy, di- (1-4C)alkoxy-(2-4C)alkyl!amino-(2-4C)alkoxy, amino-(2-4C)alkylamino-(2-4C)alkoxy, di- amino-(2-4C)alkyl!amino-(2-4C)alkoxy, (1-4C)alkylamino-(2-4C)alkylamino-(2-4C)alkoxy, di- (1-4C)alkylamino-(2-4C)alkyl!amino-(2-4C)alkoxy, di- (1-4C)alkyl!amino-(2-4C)alkylamino-(2-4C)alkoxy, di-{di- (1-4C)alkyl!amino-(2-4C)alkyl}amino-(2-4C)alkoxy, pyrrolidin-1-yl-(2-4C)alkylamino-(2-4C)alkoxy, piperidino-(2-4C)alkylamino-(2-4C)alkoxy, morpholino-(2-4C)alkylamino-(2-4C)alkoxy, piperazin-1-yl-(2-4C)alkylamino-(2-4C)alkoxy, 4-(1-4C)alkylpiperazin-1-yl-(2-4C)alkylamino-(2-4C)alkoxy, (1-4C)alkylthio-(2-4C)alkoxy, (1-4C)alkylsulphinyl-(2-4C)alkoxy, (1-4C)alkylsulphonyl-(2-4C)alkoxy, halogeno-(2-4C)alkylamino, hydroxy-(2-4C)alkylamino, (1-4C)alkoxy-(2-4C)alkylamino, amino-(2-4C)alkylamino, (1-4C)alkylamino-(2-4C)alkylamino, di- (1-4C)alkyl!amino-(2-4C)alkylamino, pyrrolidin-1-yl-(2-4C)alkylamino, piperidino-(2-4C)alkylamino, morpholino-(2-4C)alkylamino, piperazin-1-yl-(2-4C)alkylamino, 4-(1-4C)alkylpiperazin-1-yl-(2-4C)alkylamino, hydroxy-(2-4C)alkylamino-(2-4C)alkylamino, di- hydroxy-(2-4C)alkyl!amino-(2-4C)alkylamino, (1-4C)alkoxy-(2-4C)alkylamino-(2-4C)alkylamino, di- (1-4C)alkoxy-(2-4C)alkyl!amino-(2-4C)alkylamino, amino-(2-4C)alkylamino-(2-4C)alkylamino, di- amino-(2-4C)alkyl!amino-(2-4C)alkylamino, (1-4C)alkylamino-(2-4C)alkylamino-(2-4C)alkylamino, di- (1-4C)alkylamino-(2-4C)alkyl!amino-(2-4C)alkylamino, di- (1-4C)alkyl!amino-(2-4C)alkylamino-(2-4C)alkylamino, di-{di- (1-4C)alkyl!amino-(2-4C)alkyl}amino-(2-4C)alkylamino, pyrrolidin-1-yl-(2-4C)alkylamino-(2-4C)alkylamino, piperidino-(2-4C)alkylamino-(2-4C)alkylamino, morpholino-(2-4C)alkylamino-(2-4C)alkylamino, piperazin-1-yl-(2-4C)alkylamino-(2-4C)alkylamino, 4-(1-4C)alkylpiperazin-1-yl-(2-4C)alkylamino-(2-4C)alkylamino, N-(1-4C)alkyl-halogeno-(2-4C)alkylamino, N-(1-4C)alkyl-hydroxy-(2-4C)alkylamino, N-(1-4C)alkyl-(1-4C)alkoxy-(2-4C)alkylamino, di- halogeno-(2-4C)alkyl!amino, di- hydroxy-(2-4C)alkyl!amino, di- (1-4C)alkoxy-(2-4C)alkyl!amino, (2-4C)alkanoylamino, 2-oxopyrrolidin-1-yl, 2-oxopiperidin-1-yl, halogeno-(2-4C)alkanoylamino, hydroxy-(2-4C)alkanoylamino, (1-4C)alkoxy-(2-4C)alkanoylamino, (3-4C)alkenoylamino, (3-4C)alkynoylamino, (2-4C)alkanoyloxy-(2-4C)alkanoylamino, amino-(2-4C)alkanoylamino, (1-4C)alkylamino-(2-4C)alkanoylamino, di- (1-4C)alkyl!amino-(2-4C)alkanoylamino, pyrrolidin-1-yl-(2-4C)alkanoylamino, piperidino-(2-4C)alkanoylamino, morpholino-(2-4C)alkanoylamino, piperazin-1-yl-(2-4C)alkanoylamino, 4-(1-4C)alkylpiperazin-1-yl-(2-4C)alkanoylamino, (1-4C)alkylthio-(2-4C)alkanoylamino, (1-4C)alkylsulphinyl-(2-4C)alkanoylamino, (1-4C)alkylsulphonyl-(2-4C)alkanoylamino, N-(1-4C)alkyl-(2-4C)alkanoylamino, N-(1-4C)alkyl-halogeno-(2-4C)alkanoylamino, N-(1-4C)alkyl-hydroxy-(2-4C)alkanoylamino, N-(1-4C)alkyl-(1-4C)alkoxy-(2-4C)alkanoylamino, N-(1-4C)alkyl-(3-4C)alkenoylamino or N-(1-4C)alkyl-(3-4C)alkynoylamino, and wherein any of the above-mentioned R¹ substituents comprising a CH₂ (methylene) group which is not attached to a halogeno, SO or SO₂ group or to a N, O or S atom optionally bears on said CH₂ group a substituent selected from hydroxy, amino, (1-4C)alkoxy, (1-4C)alkylamino and di- (1-4C)alkyl!amino;

n is 0, 1, 2 or 3;

each R² is independently halogeno, trifluoromethyl, hydroxy, amino, nitro, cyano, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylamino, di- (1-4C)alkyl!amino or (2-4C)alkanoylamino;

X is a group of the formula CO, C(R³)₂, CH(OR³), C(R³)₂ --C(R³)₂, C(R³)═

C(R³), C.tbd.C, CH(CN), O, S, SO, SO₂, CONR³, SO₂ NR³, NR³ CO, NR³ SO₂, OC(R³)₂, SC(R³)₂, C(R³)₂ O or C(R³)₂ S wherein each R³ is independently hydrogen or (1-4C)alkyl; and

Q is a phenyl or naphthyl group or a 5- or 6-membered heteroaryl moiety containing 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulphur, which heteroaryl moiety is a single ring or is fused to a benzo ring, and wherein said phenyl or naphthyl group or heteroaryl moiety is optionally substituted with 1, 2 or 3 substituents selected from halogeno, trifluoromethyl, cyano, carbamoyl, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylamino, di- (1-4C)alkyl!amino, (2-4C)alkanoylamino, N-(1-4C)alkylcarbamoyl and N,N-di- (1-4C)alkyl!carbamoyl;

or a pharmaceutically-acceptable salt thereof.

4. An aniline derivative of the formula I as claimed in claim 1 wherein m is 1 with the substituent located at the 6-position or m is 2 with the substituents located at the 6- and 7-positions and each R¹ is hydroxy, amino, methoxy, ethoxy, acetoxy, methylamino, ethylamino, 2-bromoethoxy, 2,2,2-trifluoroethoxy, 2-hydroxyethoxy, 2-methoxyethoxy, 2-ethoxyethoxy, 2-methylaminoethoxy, 2-ethylaminoethoxy, 3-methylaminopropoxy, 3-ethylaminopropoxy, 2-dimethylaminoethoxy, 2-diethylaminoethoxy, 3-dimethylaminopropoxy, 3-diethylaminopropoxy, 2-hydroxyethylamino, 2-methoxyethylamino, 2-ethoxyethylamino, acetamido, 2-chloroacetamido, 2-methylaminoacetamido, 2-ethylaminoacetamido, 2-dimethylaminoacetamido or 2-diethylaminoacetamido, or (R¹)_m is a 6,7-methylenedioxy group;

n is 0 or n is 1 and R² is fluoro, chloro, cyano, methyl or ethyl;

X is a group of the formula CO, C(R³)₂, CH(OR³), O, S, SO₂, CONR³, SO₂ NR³, OC(R³)₂ or SC(R³)₂ wherein each R³ is independently hydrogen or methyl; and

Q is a phenyl group which is optionally substituted with 1 or 2 substituents selected from fluoro, chloro, bromo, trifluoromethyl, cyano and carbamoyl,

or Q is a 5- or 6-membered heteroaryl moiety selected from furyl, thienyl, pyridyl, oxazolyl, imidazolyl, thiazolyl, pyrimidinyl and 1,2,4-triazolyl which is optionally substituted with 1 or 2 substituents selected from fluoro, chloro, methyl, ethyl, methoxy and ethoxy;

or a pharmaceutically-acceptable salt thereof.

5. An aniline derivative of the formula I as claimed in claim 1

wherein m is 1 or 2 and each R¹ is hydroxy, methoxy, ethoxy, 2-hydroxyethoxy, 2-methoxyethoxy, 2-methylaminoethoxy or 2-dimethylaminoethoxy, or (R¹)_m is a methylenedioxy group;

n is 0 or n is 1 and R², which is located ortho to the group of formula --X--Q, is fluoro, chloro, cyano, methyl or ethyl;

X is a group of the formula CO, C(R³)₂, CH(OR³), O, S, SO₂, CONR³, SO₂ NR³, OC(R³)₂ or SC(R³)₂ wherein each R³ is independently hydrogen or methyl; and

Q is a phenyl group which is optionally substituted with 1 or 2 substituents selected from fluoro, chloro, bromo, trifluoromethyl, cyano and carbamoyl,

or Q is a 5- or 6-membered heteroaryl moiety selected from furyl, thienyl, pyridyl, oxazolyl, imidazolyl, thiazolyl, pyrimidinyl and 1,2,4-triazolyl which is optionally substituted with a substituent selected from methyl and ethyl;

or a pharmaceutically-acceptable salt thereof.

6. An aniline derivative of the formula I as claimed in claim 1 wherein m is 1 with the substituent located at the 6-position or m is 2 with the substituents located at the 6- and 7-positions and each R¹ is hydroxy, amino, methoxy, ethoxy, acetoxy, methylamino, ethylamino, 2-bromoethoxy, 2,2,2-trifluoroethoxy, 2-hydroxyethoxy, 2-methoxyethoxy, 2-methylaminoethoxy, 3-methylaminopropoxy, 2-dimethylaminoethoxy, 3-dimethylaminopropoxy, 2-(pyrrolidin-1-yl)ethoxy, 3-(pyrrolidin-1-yl)propoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(piperazin-1-yl)ethoxy, 3-(piperazin-1-yl)propoxy, 2-(4-methylpiperazin-1-yl)ethoxy, 3-(4-methylpiperazin-1-yl)propoxy, 2-hydroxyethylamino, 2-methoxyethylamino, 3-methoxypropylamino, 2-dimethylaminoethylamino, 3-dimethylaminopropylamino, 2-(pyrrolidin-1-yl)ethylamino, 3-(pyrrolidin-1-yl)propylamino, 2-piperidinoethylamino, 3-piperidinopropylamino, 2-morpholinoethylamino, 3-morpholinopropylamino, 2-(piperazin-1-yl)ethylamino, 3-(piperazin-1-yl)propylamino, 2-(4-methylpiperazin-1-yl)ethylamino, 3-(4-methylpiperazin-1-yl)propylamino, acetamido, 2-chloroacetamido, 2-methylaminoacetamido, 2-ethylaminoacetamido, 2-dimethylaminoacetamido or 2-diethylaminoacetamido, or (R¹)_m is a 6,7-methylenedioxy group;

n is 0, 1 or 2 and each R² is independently fluoro, chloro, bromo, cyano, methyl or ethyl;

X is a group of the formula CO, CH₂, CH(OH), O, S, SO₂, CONH, SO₂ NH, NHCO, NHSO₂ or OCH₂ ; and

Q is a phenyl group which is optionally substituted with 1 or 2 substituents selected from fluoro, chloro, bromo, trifluoromethyl, cyano, carbamoyl, methyl and methoxy, or Q is a 5- or 6-membered heteroaryl moiety selected from furyl, thienyl, oxazolyl, imidazolyl, thiazolyl and pyridyl which is optionally substituted with 1 or 2 substituents selected from fluoro, chloro, methyl, ethyl, methoxy and ethoxy;

or a pharmaceutically-acceptable salt thereof.

7. An aniline derivative of the formula I as claimed in claim 1 wherein (R¹)_m is 6,7-dimethoxy;

n is 1 and R², which is located ortho to the group of formula --X--Q, is fluoro, chloro or methyl.

X is a group of the formula CO, CH₂, CH(OH), O, S, SO₂, CONH, SO₂ NH or OCH₂ ; and

Q is a phenyl group which is optionally substituted with 1 or 2 substituents selected from fluoro, chloro, trifluoromethyl, cyano and carbamoyl,

or Q is 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-imidazolyl, 1-methylimidazol-2-yl, 4-imidazolyl, 1-methylimidazol-4-yl, 5-imidazolyl, 1-methylimidazol-5-yl, 2-thiazolyl, 4-thiazolyl or 5-thiazolyl;

or a pharmaceutically-acceptable acid-addition salt thereof.

8. An aniline derivative of the formula I as claimed in claim 1 wherein (R¹)_m is 6,7-dimethoxy, 6-methoxy-7-(2,2,2-trifluoroethoxy), 6-(2-dimethylaminoethoxy)-7-methoxy, 6-(3-dimethylaminopropoxy)-7-methoxy, 6-(2-morpholinoethoxy)-7-methoxy, 6-(3-morpholinopropoxy)-7-methoxy, 6-(2-dimethylaminoethoxy), 6-(3-dimethylaminopropoxy), 6-(2-morpholinoethoxy), 6-(3-morpholinopropoxy), 6-amino, 6-acetamido, 6-(2-chloroacetamido), 6-(2-methylaminoacetamido), 6-(2-methoxyethylamino, 6-(2-dimethylaminoethylamino)-7-methoxy, 6-(3-dimethylaminopropylamino)-7-methoxy, 6-(2-morpholinoethylamino)-7-methoxy or 6-(3-morpholinopropylamino)-7-methoxy;

n is 1 or 2 and R² is fluoro, chloro or methyl;

X is a group of formula OCH₂ ; and

Q is 2-furyl, 3-furyl, 2-thienyl, 2-pyridyl or 1-methylimidazol-2-yl;

or a pharmaceutically-acceptable acid-addition salt thereof.

9. An aniline derivative of the formula I as claimed in claim 1 wherein (R¹)_m is 6,7-dimethoxy;

n is 1 and R² is fluoro, chloro or methyl;

X is a group of the formula OCH₂ ; and

Q is 2-furyl, 3-furyl, 2-thienyl, 2-pyridyl or 1-methylimidazol-2-yl;

or a pharmaceutically-acceptable acid-addition salt thereof.

10. An aniline derivative of the formula I as claimed in claim 1 selected from:

4-(4-benzoyl-3-chloroanilino)-6,7-dimethoxyquinazoline,

4-{3-chloro-4- 1-hydroxy-1-(4-pyridyl)methyl!anilino}-6,7-dimethoxyquinazoline,

4-(4-benzyl-3-chloroanilino)-6,7-dimethoxyquinazoline,

4-(3-chloro-4-phenylthioanilino)-6,7-dimethoxyquinazoline,

4- 3-chloro-4-(1-methylimidazol-2-ylthio)anilino!-6,7-dimethoxyquinazoline,

6,7-dimethoxy-4- 4-(N-phenylsulphamoyl)anilino!quinazoline,

6,7-dimethoxy-4- 3-methyl-4-(2-pyridylmethoxy)anilino!quinazoline,

4- 3-chloro-4-(4-fluorobenzoyl)anilino)-6,7-dimethoxyquinazoline,

4- 2-fluoro-4-(2-pyridylmethoxy)anilino!-6,7-dimethoxyquinazoline,

4- 3-fluoro-4-(2-pyridylmethoxy)anilino!-6,7-dimethoxyquinazoline,

4- 3-chloro-4-(2-pyridylmethoxy)anilino!-6,7-dimethoxyquinazoline,

4- 3-chloro-4-(1-methylimidazol-2-ylmethoxy)anilino!-6,7-dimethoxyquinazoline,

6,7-dimethoxy-4- 3-methyl-4-(1-methylimidazol-2-ylmethoxy)anilino!quinazoline,

6,7-dimethoxy-4- 3-methyl-4-(2-thiazolylmethoxy)anilino!quinazoline,

4- 3-fluoro-4-(2-pyridylmethoxy)anilino!-6,7-dimethoxyquinazoline,

4- 2-fluoro-4-(2-pyridylmethoxy)anilino!-6-(3-morpholinopropoxy)quinazoline

6-(3-dimethylaminopropoxy)-7-methoxy-4- 3-methyl-4-(2-pyridylmethoxy)anilino!quinazoline,

7-methoxy-4- 3-methyl-4-(2-pyridylmethoxy)anilino!-6-(3-morpholinopropoxy)quinazoline or

4- 2-fluoro-4-(2-pyridylmethoxy)anilino!-6-(2-methoxyethylamino)quinazoline

or a pharmaceutically-acceptable acid-addition salt thereof.

11. A process for the preparation of an aniline derivative of the formula I, or a pharmaceutically-acceptable salt thereof, as claimed in any one of claims 1, 2, 3 and 4 to 10 which comprises:

(a) the reaction of a quinazoline derivative of the formula II ##STR7## wherein Z is a displaceable group, with an aniline of the formula III, ##STR8## (b) for the production of those compounds of the formula I wherein R¹ or R² is hydroxy, the cleavage of an aniline derivative of the formula I wherein R¹ or R² is (1-4C)alkoxy;

(c) for the production of those compounds of the formula I wherein R¹ is amino or hydroxyamino, the reduction of an aniline derivative of the formula I wherein R¹ is nitro;

(d) for the production of those compounds of the formula I wherein R¹ is (2-4C)alkanoylamino, substituted (2-4C)alkanoylamino, (3-4C)alkenoylamino, (3-4C)alkynoylamino, N-(1-4C)alkyl-(2-4C)alkanoylamino, substituted N-(1-4C)alkyl-(2-4C)-alkanoylamino, N-(1-4C)alkyl-(3-4C)alkenoylamino or N-(1-4C)alkyl-(2-4C)alkynoylamino or R² is (2-4C)alkanoylamino, the acylation of an aniline derivative of the formula I wherein R¹ or R² is amino;

(e) for the production of those compounds of the formula I wherein R¹ is (1-4C)alkoxy or substituted (1-4C)alkoxy or R¹ is (1-4C)alkylamino, di- (1-4C)alkyl!amino or substituted (1-4C)alkylamino, the alkylation of an aniline derivative of the formula I wherein R¹ is hydroxy or amino as appropriate;

(f) for the production of those compounds of the formula I wherein X is a group of the formula CH(OH) or CH₂, the reduction of a compound of the formula I wherein X is a group of the formula CO;

(g) for the production of those compounds of the formula I wherein X is a group of the formula SO or SO₂, the oxidation of an aniline derivative of the formula I wherein X is a group of the formula S;

(h) for the production of those compounds of the formula I wherein R¹ is (2-4C)alkanoyloxy, the acylation of an aniline derivative of the formula I wherein R¹ is hydroxy;

(i) for the production of those compounds of the formula I wherein R¹ is hydroxy, the hydrolysis of an aniline derivative of the formula I wherein R¹ is (2-4C)alkanoyloxy;

(j) for the production of those compounds of the formula I wherein R¹ is a (2-4C)alkoxy group which bears a hydroxy, amino, substituted hydroxy or substituted amino group, the reaction of a compound of the formula I wherein R¹ is a hydroxy-(2-4C)alkoxy group, or a reactive derivative thereof, with water, ammonia, an alcohol or an amine as appropriate;

(k) for the production of those compounds of the formula I wherein X is a group of the formula OC(R³)₂, the alkylation of a phenol of the formula IV ##STR9## with an alkylating agent of the formula Z--C(R³)₂ --Q wherein Z is a displaceable group;

or

(1) for the production of those compounds of the formula I wherein R¹ is (1-4C)alkylamino or substituted (2-4C)alkylamino, the reductive amination of formaldehyde, a (2-4C)alkanoaldehyde or a substituted (2-4C)alkanoaldehyde;

and when a pharmaceutically-acceptable salt of an aniline derivative of the formula I is required it may be obtained using a conventional procedure.

12. A pharmaceutical composition which comprises an aniline derivative of the formula I, or a pharmaceutically-acceptable salt thereof, as claimed in any one of claims 1, 2, 3 and 4 to 10 in association with a pharmaceutically-acceptable diluent or carrier.

13. A method for producing an anti-proliferative effect in a warm-blooded animal in need of such treatment which comprises administering to said animal an effective amount of an aniline derivative of the formula I, or a pharmaceutically-acceptable salt thereof, as claimed in any one of claims 1, 2, 3 and 4 to 10.

2. An aniline derivative of the formula I ##STR5## wherein:

m is 1, 2 or 3;

each R¹ is independently halogeno, hydroxy, amino, hydroxyamino, ureido, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy, (2-4C)alkanoyloxy, (2-4C)alkenyloxy, (2-4C)alkynyloxy, (1-3C)alkylenedioxy, (1-4C)alkylamino, di- (1-4C)alkyl!amino, pyrrolidin-1-yl, piperidino, morpholino, piperazin-1-yl, 4-(1-4C)alkylpiperazin-1-yl, (1-4C)alkylthio, halogeno-(2-4C)alkoxy, hydroxy-(2-4C)alkoxy, (1-4C)alkoxy-(2-4C)alkoxy, amino-(2-4C)alkoxy, (1-4C)alkylamino-(2-4C)alkoxy, di- (1-4C)alkyl!amino-(2-4C)alkoxy, pyrrolidin-1-yl-(2-4C)alkoxy, piperidino-(2-4C)alkoxy, morpholino-(2-4C)alkoxy, piperazin-1-yl-(2-4C)alkoxy, 4-(1-4C)alkylpiperazin-1-yl-(2-4C)alkoxy, hydroxy-(2-4C)alkylamino-(2-4C)alkoxy, di- hydroxy-(2-4C)alkyl!amino-(2-4C)alkoxy, (1-4C)alkoxy-(2-4C)alkylamino-(2-4C)alkoxy, di- (1-4C)alkoxy-(2-4C)alkyl!amino-(2-4C)alkoxy, amino-(2-4C)alkylamino-(2-4C)alkoxy, di- amino-(2-4C)alkyl!amino-(2-4C)alkoxy, (1-4C)alkylamino-(2-4C)alkylamino-(2-4C)alkoxy, di- (1-4C)alkylamino-(2-4C)alkyl!amino-(2-4C)alkoxy, di- (1-4C)alkyl!amino-(2-4C)alkylamino-(2-4C)alkoxy, di-{di- (1-4C)alkyl!amino-(2-4C)alkyl}amino-(2-4C)alkoxy, pyrrolidin-1-yl-(2-4C)alkylamino-(2-4C)alkoxy, piperidino-(2-4C)alkylamino-(2-4C)alkoxy, morpholino-(2-4C)alkylamino-(2-4C)alkoxy, piperazin-1-yl-(2-4C)alkylamino-(2-4C)alkoxy, 4-(1-4C)alkylpiperazin-1-yl-(2-4C)alkylamino-(2-4C)alkoxy, (1-4C)alkylthio-(2-4C)alkoxy, (1-4C)alkylsulphinyl-(2-4C)alkoxy, (1-4C)alkylsulphonyl-(2-4C)alkoxy, halogeno-(2-4C)alkylamino, hydroxy-(2-4C)alkylamino, (1-4C)alkoxy-(2-4C)alkylamino, amino-(2-4C)alkylamino, (1-4C)alkylamino-(2-4C)alkylamino, di- (1-4C)alkyl!amino-(2-4C)alkylamino, pyrrolidin-1-yl-(2-4C)alkylamino, piperidino-(2-4C)alkylamino, morpholino-(2-4C)alkylamino, piperazin-1-yl-(2-4C)alkylamino, 4-(1-4C)alkylpiperazin-1-yl-(2-4C)alkylamino, hydroxy-(2-4C)alkylamino-(2-4C)alkylamino, di- hydroxy-(2-4C)alkyl!amino-(2-4C)alkylamino, (1-4C)alkoxy-(2-4C)alkylamino-(2-4C)alkylamino, di- (1-4C)alkoxy-(2-4C)alkyl!amino-(2-4C)alkylamino, amino-(2-4C)alkylamino-(2-4C)alkylamino, di- amino-(2-4C)alkyl!amino-(2-4C)alkylamino, (1-4C)alkylamino-(2-4C)alkylamino-(2-4C)alkylamino, di- (1-4C)alkylamino-(2-4C)alkyl!amino-(2-4C)alkylamino, di- (1-4C)alkyl!amino-(2-4C)alkylamino-(2-4C)alkylamino, di-{di- (1-4C)alkyl!amino-(2-4C)alkyl}amino-(2-4C)alkylamino, pyrrolidin-1-yl-(2-4C)alkylamino-(2-4C)alkylamino, piperidino-(2-4C)alkylamino-(2-4C)alkylamino, morpholino-(2-4C)alkylamino-(2-4C)alkylamino, piperazin-1-yl-(2-4C)alkylamino-(2-4C)alkylamino, 4-(1-4C)alkylpiperazin-1-yl-(2-4C)alkylamino-(2-4C)alkylamino, N-(1-4C)alkyl-halogeno-(2-4C)alkylamino, N-(1-4C)alkyl-hydroxy-(2-4C)alkylamino, N-(1-4C)alkyl-(1-4C)alkoxy-(2-4C)alkylamino, di- halogeno-(2-4C)alkyl!amino, di- hydroxy-(2-4C)alkyl!amino, di- (1-4C)alkoxy-(2-4C)alkyl!amino, (2-4C)alkanoylamino, 2-oxopyrrolidin-1-yl, 2-oxopiperidin-1-yl, halogeno-(2-4C)alkanoylamino, hydroxy-(2-4C)alkanoylamino, (1-4C)alkoxy-(2-4C)alkanoylamino, (3-4C)alkenoylamino, (3-4C)alkynoylamino, (2-4C)alkanoyloxy-(2-4C)alkanoylamino, amino-(2-4C)alkanoylamino, (1-4C)alkylamino-(2-4C)alkanoylamino, di- (1-4C)alkyl!amino-(2-4C)alkanoylamino, pyrrolidin-1-yl-(2-4C)alkanoylamino, piperidino-(2-4C)alkanoylamino, morpholino-(2-4C)alkanoylamino, piperazin-1-yl-(2-4C)alkanoylamino, 4-(1-4C)alkylpiperazin-1-yl-(2-4C)alkanoylamino, (1-4C)alkylthio-(2-4C)alkanoylamino, (1-4C)alkylsulphinyl-(2-4C)alkanoylamino, (1-4C)alkylsulphonyl-(2-4C)alkanoylamino, N-(1-4C)alkyl-(2-4C)alkanoylamino, N-(1-4C)alkyl-halogeno-(2-4C)alkanoylamino, N-(1-4C)alkyl-hydroxy-(2-4C)alkanoylamino, N-(1-4C)alkyl-(1-4C)alkoxy-(2-4C)alkanoylamino, N-(1-4C)alkyl-(3-4C)alkenoylamino or N-(1-4C)alkyl-(3-4C)alkynoylamino, and wherein any of the above-mentioned R¹ substituents comprising a CH₂ (methylene) group which is not attached to a halogeno, SO or SO₂ group or to a N, O or S atom optionally bears on said CH₂ group a substituent selected from hydroxy, amino, (1-4C)alkoxy, (1-4C)alkylamino and di- (1-4C)alkyl!amino;

n is 0, 1, 2 or 3;

each R² is independently halogeno, trifluoromethyl, hydroxy, amino, nitro, cyano, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylamino, di- (1-4C)alkyl!amino or (2-4C)alkanoylamino;

X is a group of the formula CO, C(R³)₂, CH(OR³), C(R³)₂ --C(R³)₂, C(R³)═

C(R³), C.tbd.C, CH(CN), O, S, SO, SO₂, CONR³, SO₂ NR³, NR³ CO, NR³ SO₂, SC(R³)₂, C(R³)₂ O or C(R³)₂ S wherein each R³ is independently hydrogen or (1-4C)alkyl; and

Q is a phenyl or naphthyl group or a 5- or 6-membered heteroaryl moiety containing 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulphur, which heteroaryl moiety is a single ring or is fused to a benzo ring, and wherein said phenyl or naphthyl group or heteroaryl moiety is optionally substituted with 1, 2 or 3 substituents selected from halogeno, trifluoromethyl, cyano, carbamoyl, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylamino, di- (1-4C)alkyl!amino, (2-4C)alkanoylamino, N-(1-4C)alkylcarbamoyl and N,N-di- (1-4C)alkyl!carbamoyl;

or a pharmaceutically-acceptable salt thereof.

3. An aniline derivative of the formula I ##STR6## wherein m is 1 with the substituent located at the 6-position, or m is 2 with the substituents located at the 6- and 7-positions;

each R¹ is fluoro, chloro, bromo, hydroxy, amino, methoxy, ethoxy, acetoxy, methylamino, ethylamino, 2-bromoethoxy, 2,2,2-trifluoroethoxy, 2-hydroxyethoxy, 2-methoxyethoxy, 2-ethoxyethoxy, 2-methylaminoethoxy, 2-ethylaminoethoxy, 3-methylaminopropoxy, 3-ethylaminopropoxy, 2-dimethylaminoethoxy, 2-diethylaminoethoxy, 3-dimethylaminopropoxy, 3-diethylaminopropoxy, 2-(pyrrolidin-1-yl)ethoxy, 3-(pyrrolidin-1-yl)propoxy, 2-piperidinoethoxy, 3-piperidinopropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy, 2-(piperazin-1-yl)ethoxy, 3-(piperazin-1-yl)propoxy, 2-(4-methylpiperazin-1-yl)ethoxy, 3-(4-methylpiperazin-1-yl)propoxy, 2-hydroxyethylamino, 2-methoxyethylamino, 2-ethoxyethylamino, 3-methoxypropylamino, 2-dimethylaminoethylamino, 3-dimethylaminopropylamino, 2-(pyrrolidin-1-yl)ethylamino, 3-(pyrrolidin-1-yl)propylamino, 2-piperidinoethylamino, 3-piperidinopropylamino, 2-morpholinoethylamino, 3-morpholinopropylamino, 2-(piperazin-1-yl)ethylamino, 3-(piperazin-1-yl)propylamino, 2-(4-methylpiperazin-1-yl)ethylamino, 3-(4-methylpiperazin-1-yl)propylamino, acetamido, 2-chloroacetamido, 2-methylaminoacetamido, 2-ethylaminoacetamido, 2-dimethylaminoacetamido or 2-diethylaminoacetamido, or (R¹)_m is a 6,7-methylenedioxy group;

n is 0, 1 or 2;

each R² is independently fluoro, chloro, bromo, cyano, methyl or ethyl;

X is a group of the formula CO, C(R³)₂, CH(OR³), O, S, SO₂, CONR³, SO₂ NR³, NR³ CO, NR³ SO₂, OC(R³)₂ or SC(R³)₂ wherein each R³ is independently hydrogen or methyl; and

Q is a phenyl group which is optionally substituted with 1 or 2 substituents selected from fluoro, chloro, bromo, trifluoromethyl, cyano, carbamoyl, methyl and methoxy, or Q is a 5- or 6-membered heteroaryl moiety selected from furyl, thienyl, oxazolyl, imidazolyl, thiazolyl, pyridyl, pyrimidinyl and 1,2,4-triazolyl which is optionally substituted with 1 or 2 substituents selected from fluoro, chloro, methyl, ethyl, methoxy and ethoxy;

or a pharmaceutically-acceptable salt thereof.