Quinazoline derivatives

Claim 2

A quinazoline derivative of the formula I ##STR6## wherein m is 1, 2 or 3 and each R 1 is independently hydroxy, amino, ureido, hydroxyamino, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy, (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-(1-4C)alkyl, hydroxy-(1-4C)alkyl, (2-4C)alkanoyloxy-(1-4C)alkyl, (1-4C)alkoxy-(1-4C)alkyl, cyano-(1-4C)alkyl, amino-(1-4C)alkyl, (1-4C)alkylamino-(1-4C)alkyl, di-[(1-4C)alkyl]amino-(1-4C)alkyl, piperidino-(1-4C)alkyl, morpholino-(1-4C)alkyl, piperazin-1-yl-(1-4C)alkyl, 4-(1-4C)alkylpiperazin-1-yl-(1-4C)alkyl, hydroxy-(2-4C)alkoxy-(1-4C)alkyl, (1-4C)alkoxy-(2-4C)alkoxy-(1-4C)alkyl, hydroxy-(2-4C)alkylamino-(1-4C)alkyl, (1-4C)alkoxy-(2-4C)alkylamino-(1-4C)alkyl, halogeno-(2-4C)alkoxy, hydroxy-(2-4C)alkoxy, (2-4C)alkanoyloxy-(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, (2-4C)alkanoyloxy, hydroxy-(2-4C)alkanoyloxy, (1-4C)alkoxy-(2-4C)alkanoyloxy, phenyl-(1-4C)alkoxy, halogeno-(2-4C)alkylamino, hydroxy-(2-4C)alkylamino, (2-4C)alkanoyloxy-(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, (2-4C)alkanoylamino, (1-4C)alkoxycarbonylamino, benzamido, 3-phenylureido, halogeno-(2-4C)alkanoylamino, hydroxy-(2-4C)alkanoylamino or (1-4C)alkoxy-(2-4C)alkanoylamino, and wherein said benzamido substituent or any phenyl group in a R 1 substituent may optionally bear one or two halogeno, (1-4C)alkyl or (1-4C)alkoxy substituents; and Q is a 9- or 10-membered bicyclic heterocyclic moiety, or a hydrogenated derivative thereof, containing one or two nitrogen heteroatoms and optionally containing a further heteroatom selected from nitrogen, oxygen and sulphur, which heterocyclic moiety, or a hydrogenated derivative thereof, may optionally bear one or two substituents selected from halogeno, hydroxy, oxo, amino, nitro, carbamoyl, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylamino, di-[(1-4C)alkyl]amino and (2-4C)alkanoylamino; or a pharmaceutically-acceptable salt thereof.

Claim 3

A quinazoline derivative of the formula I ##STR7## wherein m is 1, 2 or 3 and each R 1 is independently hydrogen, halogeno, nitro, hydroxy, amino, ureido, hydroxyamino, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy, (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-(1-4C)alkyl, hydroxy-(1-4C)alkyl, (2-4C)alkanoyloxy-(1-4C)alkyl, (1-4C)alkoxy-(1-4C)alkyl, cyano-(1-4C)alkyl, amino-1-4C)alkyl, (1-4C)alkylamino-(1-4C)alkyl, di [(1-4C)alkyl ]amino-(1-4C)alkyl, piperidino-(1-4C)alkyl, morpholino-(1-4C)alkyl, piperazin-1-yl (1-4C)alkyl, 4-(1-4C)alkylpiperazin-1-yl-(1-4C)alkyl, hydroxy-(2-4C)alkoxy-(1-4C)alkyl, (1-4C)alkoxy(2-4C)alkoxy-(1-4C)alkyl, hydroxy-(2-4C)alkylamino-(1-4C)alkyl, (1-4C)alkoxy-(2-4C)alkylamino-(1-4C)alkyl, halogeno-(2-4C)alkoxy, hydroxy-(2-4C)alkoxy, (2-4C)alkanoyloxy-(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, (2-4C)alkanoyloxy, hydroxy-(2-4C)alkanoyloxy, (1-4C)alkoxy-(2-4C)alkanoyloxy, phenyl-(1-4C)alkoxy, halogeno-(2-4C)alkylamino, hydroxy-(2-4C)alkylamino, (2-4C)alkanoyloxy-(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, (2-4C)alkanoylamino, (1-4C)alkoxycarbonylamino, benzamido, 3-phenylureido, halogeno-(2-4C)alkanoylamino, hydroxy-(2-4C)alkanoylamino or (1-4C)alkoxy-(2-4C)alkanoylamino, and wherein said benzamido substituent or any phenyl group in a R 1 substituent may optionally bear one or two halogeno, (1-4C)alkyl or (1-4C)alkoxy substituents; and Q is a 9- or 10-membered bicyclic heterocyclic moiety, or a hydrogenated derivative thereof, containing one or two nitrogen heteroatoms and optionally containing a further heteroatom selected from nitrogen, oxygen and sulphur, which heterocyclic moiety, or a hydrogenated derivative thereof, may optionally bear one or two substituents selected from carboxy, (1-4C)alkoxycarbonyl, halogeno, hydroxy, oxo, amino, nitro, carbamoyl, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylamino, di-[(1-4C)alkyl]amino and (2-4C)alkanoylamino; or a pharmaceutically-acceptable salt thereof; except that 4-(4-quinazolinylamino)quinazoline is excluded.

Claim 4

A quinazoline derivative of the formula I ##STR7## wherein m is 1, 2 or 3 and each R 1 is independently hydrogen, halogeno, nitro, hydroxy, amino, ureido, hydroxyamino, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy, (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-(1-4C)alkyl, hydroxy-(1-4C)alkyl, (2-4C)alkanoyloxy-(1-4C)alkyl, (1-4C)alkoxy-(1-4C)alkyl, cyano-(1-4C)alkyl, amino-1-4C)alkyl, (1-4C)alkylamino-(1-4C)alkyl, di [(1-4C)alkyl ]amino-(1-4C)alkyl, piperidino-(1-4C)alkyl, morpholino-(1-4C)alkyl, piperazin-1-yl (1-4C)alkyl, 4-(1-4C)alkylpiperazin-1-yl-(1-4C)alkyl, hydroxy-(2-4C)alkoxy-(1-4C)alkyl, (1-4C)alkoxy(2-4C)alkoxy-(1-4C)alkyl, hydroxy-(2-4C)alkylamino-(1-4C)alkyl, (1-4C)alkoxy-(2-4C)alkylamino-(1-4C)alkyl, halogeno-(2-4C)alkoxy, hydroxy-(2-4C)alkoxy, (2-4C)alkanoyloxy-(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, (2-4C)alkanoyloxy, hydroxy-(2-4C)alkanoyloxy, (1-4C)alkoxy-(2-4C)alkanoyloxy, phenyl-(1-4C)alkoxy, halogeno-(2-4C)alkylamino, hydroxy-(2-4C)alkylamino, (2-4C)alkanoyloxy-(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, (2-4C)alkanoylamino, (1-4C)alkoxycarbonylamino, benzamido, 3-phenylureido, halogeno-(2-4C)alkanoylamino, hydroxy-(2-4C)alkanoylamino or (1-4C)alkoxy-(2-4C)alkanoylamino, and wherein said benzamido substituent or any phenyl group in a R 1 substituent may optionally bear one or two halogeno, (1-4C)alkyl or (1-4C)alkoxy substituents; and Q is a 9- or 10-membered bicyclic heterocyclic moiety, or a hydrogenated derivative thereof, containing one or two nitrogen heteroatoms and optionally containing a further heteroatom selected from nitrogen, oxygen and sulphur, which heterocyclic moiety, or a hydrogenated derivative thereof, may optionally bear one or two substituents selected from carboxy, (1-4C)alkoxycarbonyl, halogeno, hydroxy, oxo, amino, nitro, carbamoyl, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylamino, di-[(1-4C)alkyl]amino and (2-4C)alkanoylamino; or a pharmaceutically-acceptable salt thereof; except that 4-(4-quinazolinylamino)quinazoline is excluded.

Claim 5

A quinazoline derivative of the formula I ##STR8## wherein M is 1, 2 or 3 and each R 1 is independently hydrogen, halogeno, nitro, hydroxy, amino, ureido, hydroxyamino, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy, (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-(1-4C)alkyl, hydroxy-(1-4C)alkyl, (2-4C)alkanoyloxy-(1-4C)alkyl, (1-4C)alkoxy-(1-4C)alkyl, cyano-(1-4C)alkyl, amino-1-4C)alkyl, (1-4C)alkylamino-(1-4C)alkyl, di[(1-4C)alkyl]amino-(1-4C)alkyl, piperidino-(1-4C)alkyl, morpholino-(1-4C)alkyl, piperazin-1-yl-(1-4C)alkyl, 4-(1-4C)alkylpiperazin-1-yl-(1-4C)alkyl, hydroxy-(2-4C)alkoxy-(1-4C)alkyl, (1-4C)alkoxy-(2-4C)alkoxy-(1-4C)alkyl, hydroxy-(2-4C)alkylamino-(1-4C)alkyl, (1-4C)alkoxy-(2-4C)alkylamino-(1-4C)alkyl, halogeno-(2-4C)alkoxy, hydroxy-(2-4C)alkoxy, (2-4C)alkanoyloxy-(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, (2-4C)alkanoyloxy, hydroxy-(2-4C)alkanoyloxy, (1-4C)alkoxy-(2-4C)alkanoyloxy, phenyl-(1-4C)alkoxy, halogeno-(2-4C)alkylamino, hydroxy-(2-4C)alkylamino, (2-4C)alkanoyloxy-(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, (2-4C)alkanoylamino, (1-4C)alkoxycarbonylamino, benzamido, 3-phenylureido, halogeno-(2-4C)alkanoylamino, hydroxy-(2-4C)alkanoylamino, (1-4C)alkoxy-(2-4C)alkanoylamino, 2-oxopyrrolidin-1-yl or 2-oxopiperidin-1-yl, and wherein said benzamido substituent or any phenyl group in a R 1 substituent may optionally bear one or two halogeno, (1-4C)alkyl or (1-4C)alkoxy substituents; and Q is a 9- or 10-membered bicyclic heterocyclic moiety, or a hydrogenated derivative thereof, containing one or two nitrogen heteroatoms and optionally containing a further heteroatom selected from nitrogen, oxygen and sulphur, which heterocyclic moiety, or a hydrogenated derivative thereof, may optionally bear one or two substituents selected from cyano, carboxy, (1-4C)alkoxycarbonyl, halogeno, hydroxy, oxo, amino, nitro, carbamoyl, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylamino, di-[(1-4C)alkyl]amino and (2-4C)alkanoylamino; or a pharmaceutically-acceptable salt thereof; except that 4-(4-quinazolinylamino)quinazoline is excluded.

Claim 6

A quinazoline derivative of the formula I ##STR8## wherein M is 1, 2 or 3 and each R 1 is independently hydrogen, halogeno, nitro, hydroxy, amino, ureido, hydroxyamino, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy, (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-(1-4C)alkyl, hydroxy-(1-4C)alkyl, (2-4C)alkanoyloxy-(1-4C)alkyl, (1-4C)alkoxy-(1-4C)alkyl, cyano-(1-4C)alkyl, amino-1-4C)alkyl, (1-4C)alkylamino-(1-4C)alkyl, di[(1-4C)alkyl]amino-(1-4C)alkyl, piperidino-(1-4C)alkyl, morpholino-(1-4C)alkyl, piperazin-1-yl-(1-4C)alkyl, 4-(1-4C)alkylpiperazin-1-yl-(1-4C)alkyl, hydroxy-(2-4C)alkoxy-(1-4C)alkyl, (1-4C)alkoxy-(2-4C)alkoxy-(1-4C)alkyl, hydroxy-(2-4C)alkylamino-(1-4C)alkyl, (1-4C)alkoxy-(2-4C)alkylamino-(1-4C)alkyl, halogeno-(2-4C)alkoxy, hydroxy-(2-4C)alkoxy, (2-4C)alkanoyloxy-(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, (2-4C)alkanoyloxy, hydroxy-(2-4C)alkanoyloxy, (1-4C)alkoxy-(2-4C)alkanoyloxy, phenyl-(1-4C)alkoxy, halogeno-(2-4C)alkylamino, hydroxy-(2-4C)alkylamino, (2-4C)alkanoyloxy-(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, (2-4C)alkanoylamino, (1-4C)alkoxycarbonylamino, benzamido, 3-phenylureido, halogeno-(2-4C)alkanoylamino, hydroxy-(2-4C)alkanoylamino, (1-4C)alkoxy-(2-4C)alkanoylamino, 2-oxopyrrolidin-1-yl or 2-oxopiperidin-1-yl, and wherein said benzamido substituent or any phenyl group in a R 1 substituent may optionally bear one or two halogeno, (1-4C)alkyl or (1-4C)alkoxy substituents; and Q is a 9- or 10-membered bicyclic heterocyclic moiety, or a hydrogenated derivative thereof, containing one or two nitrogen heteroatoms and optionally containing a further heteroatom selected from nitrogen, oxygen and sulphur, which heterocyclic moiety, or a hydrogenated derivative thereof, may optionally bear one or two substituents selected from cyano, carboxy, (1-4C)alkoxycarbonyl, halogeno, hydroxy, oxo, amino, nitro, carbamoyl, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylamino, di-[(1-4C)alkyl]amino and (2-4C)alkanoylamino; or a pharmaceutically-acceptable salt thereof; except that 4-(4-quinazolinylamino)quinazoline is excluded.

Claim 7

A quinazoline derivative of the formula I as claimed in claim 1 or claim 2 wherein m is 1, 2 or 3 and each R 1 is independently hydroxy, amino, fluoro, chloro, nitro, methyl, ethyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, methylenedioxy, ethylenedioxy, methylamino, ethylamino, dimethylamino, diethylamino, pyrrolidin-1-yl, piperidino, morpholino, piperazin-1-yl, 4-methylpiperazin-1-yl, methylthio, ethylthio, acetamido, propionamido or 2-chloroacetamido; and Q is indolyl, 1H-benzimidazolyl, 1H-indazolyl, benzoxazolyl, benzothiazolyl, 1H-benzotriazolyl, benzo[c]furazanyl, benzo[c][2,1,3]thiadiazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl or, quinoxalinyl, which may optionally bear one or two substituents selected from fluoro, chloro, hydroxy, amino, carboxy, methyl, ethyl, methoxy, ethoxy, methylamino, dimethylamino, acetamido, methoxycarbonyl and ethoxycarbonyl; or a pharmaceutically-acceptable salt thereof.

Claim 8

A quinazoline derivative of the formula I as claimed in claim 1 or claim 2 wherein (R 1 ) m is 6-hydroxy, 7-hydroxy, 6,7-dihydroxy, 6-amino, 7-amino, 6-fluoro, 7-fluoro, 6-chloro, 7-chloro, 6-nitro, 6-methoxy, 7-methoxy, 6,7-dimethoxy, 6,7-diethoxy, 6-hydroxy-7-methoxy, 6,7-methylenedioxy, 6,7-ethylenedioxy, 6-methylamino, 7-methylamino, 6-ethylamino, 6-dimethylamino, 7-dimethylamino, 6-diethylamino, 6-pyrrolidin-1-yl, 7-pyrrolidin-1-yl, 6-piperidino, 7-piperidino, 6-morpholino, 7-morpholino, 6-piperazin-1-yl, 7-piperazin-1-yl, 6-(4-methylpiperazin-1-yl), 7-(4-methylpiperazin-1-yl), 6-methylthio, 7-methylthio, 6-amino-7-methoxy, 6-amino-7-methylamino, 6-acetamido, 7-acetamido, 6-(2-chloroacetamido) or 7-(2-chloroacetamido); and Q is 4-, 5- or 6-indolyl, 1H-benzimidazol-4-yl, 1H-benzimidazol-5-yl, 1H-benzimidazol-6-yl, 1H-indazol-4-yl, 1H-indazol-5-yl, 1H-indazol-6-yl, 1H-indazol-7-yl, 5- or 6-benzoxazolyl, 5- or 6-benzothiazolyl, 1H-benzotriazol-4-yl, 1H-benzotriazol-5-yl, 1H-benzotriazol-6-yl, benzo[c][2,1,3]thiadiazol-4-yl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 4-, 5-, 6-, 7- or 8-cinnolinyl, 5-, 6-, 7- or 8-quinazolinyl or 2-, 5- or 6-quinoxalinyl, which may optionally bear one or two substituents selected from fluoro, chloro, methyl, ethyl and methoxy; or a pharmaceutically-acceptable salt thereof.

Claim 9

A quinazoline derivative of the formula I as claimed in claim 1 wherein (R 1 ) m is 6-amino, 6,7-dimethoxy, 6-piperidino or 6-acetamido; and Q is 5-indolyl, 1H-indazol-5-yl, 6-benzothiazolyl, 1H-benzotriazol-5-yl, benzo[c][2,1,3]thiadiazol-4-yl, 5-quinolyl, 6-quinolyl, 8-quinolyl, 5-isoquinolyl or 5-quinoxalinyl; or a pharmaceutically-acceptable salt thereof.

Claim 10

A quinazoline derivative of the formula I as claimed in claim 1 selected from: 6,7-dimethoxy-4-(5-quinolylamino)quinazoline, 6,7-dimethoxy-4-(6-quinolylamino)quinazoline, 6,7-dimethoxy-4-(5-isoquinolylamino)quinazoline, 6,7-dimethoxy-4-(5-indolylamino)quinazoline, 6,7-dimethoxy-4-[(1H-indazol-5-yl)amino]quinazoline, 4-(6-benzothiazolylamino)-6,7-dimethoxyquinazoline and 4-[(benzo[c][2,1,3]thiadiazol-4-yl)amino]-6,7-dimethoxyquinazoline; or a pharmaceutically-acceptable acid-addition salt thereof.

Claim 11

A pharmaceutical composition which comprises a quinazoline derivative of the formula I, or a pharmaceutically-acceptable salt thereof, as claimed in any one of claims 1-7 in association with a pharmaceutically-acceptable diluent or carrier.