Claims for Patent: RE42353

Summary for Patent: RE42353

Title:	Quinazoline derivatives and pharmaceutical compositions containing them
Abstract:	The invention relates to quinazoline derivatives of formula (1) ##STR00001## wherein m is an integer from 1 to 2; R.sup.1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C.sub.1-3alkyl, C.sub.1-3alkoxy, C.sub.1-3alkylthio, or --NR.sup.5R.sup.6 (wherein R.sup.5 and R.sup.6, which may be the same or different, each represents hydrogen or C.sub.1-3alkyl); R.sup.2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R.sup.3 represents hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3alkoxy, C.sub.1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X.sup.1 represents --O--, --CH.sub.2--, --S--, --SO--, --SO.sub.2--, --NR.sup.7CO--, --CONR.sup.8--, --SO.sub.2NR.sup.9--, --NR.sup.10SO.sub.2-- or --NR.sup.11-- (wherein R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 each independently represents hydrogen, C.sub.1-3alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl); R.sup.4 represents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted group selected from alkyl and a 5 or 6 membered saturated carbocyclic or heterocyclic group, and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
Inventor(s):	Thomas; Andrew Peter (Macclesfield, GB), Johnstone; Craig (Macclesfield, GB), Clayton; Edward (Macclesfield, GB), Stokes; Elaine Sophie Elizabeth (Macclesfield, GB), Lohmann; Jean-Jacques Marcel (Reims Cedex, FR), Hennequin; Laurent Francois Andre (Reims Cedex, FR)
Assignee:	AstraZeneca UK Limited (London, GB)
Application Number:	12/170,027
Patent Claims:	1. A quinazoline derivative of the formula I: ##STR00027## wherein: m is an integer from 1 to 2; R.sup.1 represents hydrogen, hydroxy, halogeno, .[.nitro,.]. trifluoromethyl, cyano, C.sub.1-3alkyl, C.sub.1-3alkoxy, C.sub.1-3alkylthio, or --NR.sup.5R.sup.6 (wherein R.sup.5 and R.sup.6, which may be the same or different, each represents hydrogen or C.sub.1-3alkyl); R.sup.2 represents hydrogen, hydroxy, halogeno, methoxy.[.,.]. .Iadd.or .Iaddend.amino.[.or nitro.].; R.sup.3 represents hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3alkoxy, C.sub.1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X.sup.1 represents .[.--O--,.]. .Iadd.--O--;.Iaddend. R.sup.4 is selected from one of the following eleven groups: 1) C.sub.1-5alkylR.sup.12 (wherein R.sup.12 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group is linked to C.sub.1-5alkyl through a carbon atom and which heterocyclic group may bear one or two .[.substituent.]. .Iadd.substituents .Iaddend.selected from oxo, hydroxy, halogeno, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl, C.sub.1-4alkoxy, carbamoyl, C.sub.1-4alkylcarbamoyl, N,N-di(C.sub.1-4alkyl)carbamoyl, C.sub.1-4alkanoyl and C.sub.1-4alkoxycarbonyl) or C.sub.1-5alkylR.sup.13 (wherein R.sup.13 is a group selected from pyrrolidin-1-yl, imidazolidin-1-yl and thiomorpholino, which group may bear one or two .[.substituent.]. .Iadd.substituents .Iaddend.selected from oxo, hydroxy, halogeno, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl, C.sub.1-4alkoxy, carbamoyl, C.sub.1-4alkylcarbamoyl, N,N-di(C.sub.1-4alkyl)carbamoyl, C.sub.1-4alkanoyl and C.sub.1-4alkoxycarbonyl); 2) C.sub.2-5alkenylR.sup.14 (wherein R.sup.14 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or two .[.substituent.]. .Iadd.substituents .Iaddend.selected from oxo, hydroxy, halogeno, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl, C.sub.1-4alkoxy, carbamoyl, C.sub.1-4alkylcarbamoyl, N,N-di(C.sub.1-4alkyl)carbamoyl, C.sub.1-4alkanoyl and C.sub.1-4alkoxycarbonyl); 3) C.sub.3-5alkynylR.sup.15 (wherein R.sup.15 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or two .[.substituent.]. .Iadd.substituents .Iaddend.selected from oxo, hydroxy, halogeno, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl, C.sub.1-4alkoxy, carbamoyl, C.sub.1-4alkylcarbamoyl, N,N-di(C.sub.1-4alkyl)carbamoyl, C.sub.1-4alkanoyl and C.sub.1-4alkoxycarbonyl); 4) C.sub.1-5alkylX.sup.2C.sub.1-5alkylX.sup.3R.sup.16 (wherein X.sup.2 and X.sup.3 which may be the same or different are each --O--, --S--, --SO--, --SO.sub.2--, --NR.sup.17CO--, --CONR.sup.18--, --SO.sub.2NR.sup.19--, --NR.sup.20SO.sub.2-- or --NR.sup.21-- (wherein R.sup.17, R.sup.18, R.sup.19, R.sup.20 and R.sup.21 each independently represents hydrogen, C.sub.1-3alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl) and R.sup.16 represents hydrogen or C.sub.1-3alkyl); 5) C.sub.1-5alkylX.sup.4COR.sup.22 (wherein X.sup.4 represents --O-- or --NR.sup.23-- (wherein R.sup.23 represents hydrogen, C.sub.1-3alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl) and R.sup.22 represents --NR.sup.24R.sup.25 or --OR.sup.26 (wherein R.sup.24, R.sup.25 and R.sup.26 which may be the same or different each represents hydrogen, C.sub.1-4alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl)); 6) C.sub.1-5alkylX.sup.5R.sup.27 (wherein X.sup.5 represents --O--, --S--, --SO--, --SO.sub.2--, --OCO--, --NR.sup.28CO--, --CONR.sup.29--, --SO.sub.2NR.sup.30--, --NR.sup.31SO.sub.2-- or --NR.sup.32-- (wherein R.sup.28, R.sup.29, R.sup.30, R.sup.31 and R.sup.32 each independently represents hydrogen, C.sub.1-3alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl) or X.sup.5 is carbonyl, and R.sup.27 represents cyclopentyl, cyclohexyl or a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which cyclopentyl, cyclohexyl or heterocyclic group may bear one or two .[.substituent.]. .Iadd.substituents .Iaddend.selected from oxo, hydroxy, halogeno, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl, C.sub.1-4alkoxy, carbamoyl, C.sub.1-4alkylcarbamoyl, N,N-di(C.sub.1-4alkyl)carbamoyl, C.sub.1-4alkanoyl and C.sub.1-4alkoxycarbonyl or R.sup.27 is .[.C.sub.1-3allyl.]. .Iadd.C.sub.1-3alkyl .Iaddend.with the proviso that when R.sup.27 is C.sub.1-3alkyl, X.sup.5 is --S--, --SO--, --SO.sub.2--, --SO.sub.2NR.sup.30-- .[.or --NR.sup.31SO.sub.2--.]. .Iadd.or --NR.sup.31SO.sub.2--).Iaddend.; 7) C.sub.1-3alkoxyC.sub.2-4alkyl or C.sub.1-4alkyl; 8) C.sub.1-5alkylX.sup.6C.sub.1-5alkylR.sup.33 (wherein X.sup.6 represents --O--, --S--, --SO--, --SO.sub.2--, --NR.sup.34CO--, --CONR.sup.35--, --SO.sub.2NR.sup.36--, --NR.sup.37SO.sub.2-- or --NR.sup.38-- (wherein R.sup.34, R.sup.35, R.sup.36, R.sup.37 and R.sup.38 each independently represents hydrogen, C.sub.1-3alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl) and R.sup.33 represents cyclopentyl, cyclohexyl or a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which cyclopentyl, cyclohexyl or heterocyclic group may bear one or two .[.substitutes.]. .Iadd.substituents .Iaddend.selected from oxo, hydroxy, halogeno, .[.C.sub.1-4alkyl),.]. .Iadd.C.sub.1-4alkyl, .Iaddend.C.sub.1-4hydroxyalkyl, C.sub.1-4alkoxy, carbamoyl, C.sub.1-4alkylcarbamoyl, N,N-di(C.sub.1-4alkyl)carbamoyl, C.sub.1-4alkanoyl and C.sub.1-4alkoxycarbonyl); 9) R.sup.39 (wherein R.sup.39 is a group selected from pyrrolidin-3-yl, .[.piperidine-3-yl and piperidine-4-yl.]. .Iadd.piperidin-3-yl and piperidin-4-yl .Iaddend.which group may bear one or two .[.substituent.]. .Iadd.substituents .Iaddend.selected from oxo, hydroxy, halogeno, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl, C.sub.1-4alkoxy, carbamoyl, C.sub.1-4alkylcarbamoyl, N,N-di(C.sub.1-4alkyl)carbamoyl, C.sub.1-4alkanoyl and C.sub.1-4alkoxycarbonyl); 10) C.sub.1-5alkylR.sup.40 (wherein R.sup.40 is piperazin-1-yl which bears at least one substituent selected from C.sub.1-4alkanoyl, C.sub.1-4alkoxycarbonyl, C.sub.1-4hydroxyalkyl and --CONR.sup.41R.sup.42 (wherein R.sup.41 and R.sup.42 each independently represents hydrogen .[.or C.sub.1-4alkyl).]. .Iadd.or C.sub.1-4alkyl)).Iaddend.; and 11) C.sub.1-5alkylR.sup.44 (wherein R.sup.44 is morpholino which bears at least one and optionally two .[.substituent.]. .Iadd.substituents .Iaddend.selected from oxo, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl, carbamoyl, C.sub.1-4alkylcarbamoyl, N,N-di(C.sub.1-4alkyl)carbamoyl, C.sub.1-4alkanoyl and C.sub.1-4alkoxycarbonyl); with the further proviso that when R.sup.4 is selected from group 7) .[.R.sup.1 and/or R.sup.2 is/are nitro or.]. at least one R.sup.3 is C.sub.1-3alkanoyloxy; or a salt thereof. 2. A quinazoline derivative as claimed in claim 1 wherein R.sup.1 represents hydrogen, hydroxy, cyano, .[.nitro,.]. trifluoromethyl, methyl, ethyl, methoxy or ethoxy. 3. A quinazoline derivative as claimed in claim 1 or claim 2 wherein R.sup.2 is hydrogen. 4. A quinazoline derivative as claimed in claim 1 or claim 2 wherein the phenyl group bearing (R.sup.3).sub.m is of the formula II: ##STR00028## wherein: R.sup.a represents hydrogen, methyl, fluoro, or chloro; R.sup.b represents hydrogen, methyl, methoxy, bromo, fluoro or chloro; R.sup.c represents hydrogen or hydroxy; R.sup.d represents hydrogen, fluoro or chloro. 5. A quinazoline derivative as claimed in claim 1 or claim 2 wherein R.sup.4 is selected from one of the following nine groups: 1) C.sub.1-4alkylR.sup.12 (wherein R.sup.12 is a group selected from 1,3-dioxolan-2-yl, 1,3-dioxan-2-yl, 1,3-dithiolan-2-yl, 1,3-dithian-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, .[.piperidine-2-yl, piperidine-3-yl, piperidine-4-yl,.]. .Iadd.piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, .Iaddend.morpholin-2-yl, morpholin-3-yl and piperazin-2-yl which group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.2-3alkanoyl and C.sub.1-3alkoxycarbonyl) or C.sub.2-4alkylR.sup.45 (wherein R.sup.45 is a group selected from .[.imidazolidine-1-yl,.]. .Iadd.imidazolidin-1-yl, .Iaddend.pyrrolidin-1-yl and thiomorpholino which group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.2-3alkanoyl and C.sub.1-3alkoxycarbonyl); 2) 1-R.sup.46prop-1-en-3-yl, 1-R.sup.46but-2-en-4-yl, .[.1-but-1-en-3-yl,.]. .Iadd.1-R.sup.46but-1-en-3-yl, .Iaddend.1-R.sup.46pent-2-en-4-yl or 2-R.sup.46pent-3-en-5yl (wherein R.sup.46 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group is linked to the alkenyl group through a carbon atom and which heterocyclic group may bear one or two .[.substituent.]. .Iadd.substituents .Iaddend.selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.2-3alkanoyl and C.sub.1-3alkoxycarbonyl) or 1-R.sup.47but-2-en-4-yl, 1-R.sup.47pent-2-en-4-yl or 2-R.sup.47pent-3-en-5-yl (wherein R.sup.47 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, of which one is N and the other is selected independently from O, S and N, which heterocyclic group is linked to the alkenyl group through a nitrogen atom and which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.2-3alkanoyl and C.sub.1-3alkoxycarbonyl); 3) 1-R.sup.48prop-1-yn-3-yl, 1-R.sup.48but-2-yn-4-yl, 1-R.sup.48but-1-yn-3-yl, 1-R.sup.48pent-2-yn-4-yl or 2-R.sup.48pent-3-yn-5-yl (wherein R.sup.48 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group is linked to the alkynyl group through a carbon atom and which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.2-3alkanoyl and C.sub.1-3alkoxycarbonyl) or 1-R.sup.49but-2-yn-4-yl, 1-R.sup.49pent-2-yn-4-yl or 2-R.sup.49pent-3-yn-5-yl (wherein R.sup.49 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, of which one is N and the other is selected independently from O, S and N, which heterocyclic group is linked to the alkynyl group through a nitrogen atom and which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, N,N-di(C.sub.1-3alkylcarbamoyl, C.sub.2-3alkanoyl and C.sub.1-3alkoxycarbonyl); 4) C.sub.2-3alkylX.sup.2C.sub.1-3alkylX.sup.3R.sup.16 (wherein X.sup.2 and X.sup.3 are as defined in claim 1 and R.sup.16 represents hydrogen or C.sub.1-3alkyl); 5) C.sub.2-3alkylX.sup.4COR.sup.22 (wherein X.sup.4 is as defined in claim 1 and R.sup.22 represents --NR.sup.24R.sup.25 or --OR.sup.26 (wherein R.sup.24, R.sup.25 and R.sup.26 which may be the same or different each represents hydrogen, C.sub.1-4alkyl or C.sub.1-2alkoxyethyl)); 6) C.sub.2-3alkylX.sup.5R.sup.27 (wherein X.sup.5 is as defined in claim 1 and R.sup.27 represents a group selected from cyclopentyl, cyclohexyl, pyrrolidinyl and piperidinyl which group is linked to X.sup.5 through a carbon atom and which group may carry one substituent selected from oxo, hydroxy, halogeno, C.sub.1-2alkyl, C.sub.1-2hydroxyalkyl, C.sub.1-2alkoxy, carbamoyl, C.sub.1-2alkylcarbamoyl, N,N-di(C.sub.1-2alkyl)carbamoyl, acetyl and C.sub.1-2alkoxycarbonyl or R.sup.27 is C.sub.1-3alkyl with the proviso that when R.sup.27 is C.sub.1-3alkyl, X.sup.5 is --S--, --SO--, --SO.sub.2--, --SO.sub.2N.sup.30-- or --NR.sup.31SO.sub.2--); 7) C.sub.2-3alkylX.sup.6C.sub.2-3alkyl.sup.33 (wherein X.sup.6 is as defined in claim 1 and R.sup.33 represents a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or two .[.substituent.]. .Iadd.substituents .Iaddend.selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.2-3alkanoyl, and C.sub.1-3alkoxycarbonyl); 8) C.sub.2-3alkylR.sup.40 .Iadd.(wherein R.sup.40 .Iaddend.is piperazin-1-yl which bears at least one substituent selected from acetyl, C.sub.1-2alkoxycarbonyl, C.sub.1-2hydroxyalkyl and CONR.sup.41R.sup.42 (wherein R.sup.41 and R.sup.42 each independently represents hydrogen .[.or C.sub.1-2alkyl).]. .Iadd.or C.sub.1-2alkyl)).Iaddend.; and 9) C.sub.2-3alkylR.sup.44 .Iadd.(wherein R.sup.44 .Iaddend.is morpholino which bears at least one and optionally two substituents selected from oxo, .[.C.sub.1-2alky,.]. .Iadd.C.sub.1-2alkyl, .Iaddend.C.sub.1-2hydroxyalkyl, carbamoyl, C.sub.1-2alkylcarbamoyl, N,N-di(C.sub.1-2alkyl)carbamoyl, .[.acaetyl.]. .Iadd.acetyl .Iaddend.and C.sub.1-2alkoxycarbonyl). 6. A quinazoline derivative as claimed in claim 5 wherein R.sup.4 is selected from one of the following seven groups: 1) .[.C.sub.1-3alkylR.sup.12.]. .Iadd.C.sub.1-3alkylR.sup.12 .Iaddend.(wherein R.sup.12 is a group selected from 1,3-dioxolan-2-yl, 1,3-dioxan-2-yl, 1,3-dithiolan-2-yl, 1,3-dithian-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl and piperazin-2-yl which group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-2alkyl, C.sub.1-2hydroxyalkyl, C.sub.1-2alkoxy, carbamoyl, C.sub.1-2alkylcarbamoyl, N,N-di(C.sub.1-2alkyl)carbamoyl, acetyl and C.sub.1-2alkoxycarbonyl) or C.sub.2-3alkylR.sup.45 (wherein R.sup.45 is a group selected from imidazolidin-1-yl, pyrrolidin-1-yl and thiomorpholino which group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-2alkyl, C.sub.1-2hydroxyalkyl, C.sub.1-2alkoxy, carbamoyl, C.sub.1-2alkylkcarbamoyl, N,N-di(C.sub.1-2alkyl)carbamoyl, acetyl and C.sub.1-2alkoxycarbonyl); 2) 1-R.sup.50but-2-en-4-yl (wherein R.sup.50 is a group selected from imidazolidin-1-yl, 1,3-dioxolan-2-yl, 1,3-dioxan-2-yl, 1,3-dithiolan-2-yl, 1,3-dithian-2-yl, piperidin-4-yl, pyrrolidin-1-yl, pyrrolidin-3-yl, piperazin-1-yl, morpholino, thiomorpholino and piperidino which group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-2alkyl, C.sub.1-2hydroxyalkyl, C.sub.1-2alkoxy, carbamoyl, C.sub.1-2alkylcarbamoyl, N,N-di(C.sub.1-2alkyl)carbamoyl, acetyl and C.sub.1-2alkoxycarbonyl). 3) 1-R.sup.51but-2-yn-4-yl (wherein R.sup.51 is a group selected from imidazolidin-1-yl, 1,3-dioxolan-2-yl, 1,3-dioxan-2-yl, 1,3-dithiolan-2-yl, 1,3-dithian-2-yl, piperidin-4-yl, pyrrolidin-1-yl, pyrrolidin-3-yl, piperazin-1-yl morpholino, thiomorpholino and piperidino which group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-2alkyl, C.sub.1-2hydroxyalkyl, C.sub.1-2alkoxy, carbamoyl, C.sub.1-2alkylcarbamoyl, N,N-di(C.sub.1-2alkyl)carbamoyl, acetyl and C.sub.1-2alkoxycarbonyl); 4) C.sub.2-3alkylX.sup.2C.sub.1-3alkylX.sup.3R.sup.16 (wherein X.sup.2 and X.sup.3 are as defined in claim 1 and R.sup.16 represents hydrogen or C.sub.1-3alkyl); 5) 2-(3,3-dimethylureido)ethyl, .[.3-(3,3dimethylureido)propyl,.]. .Iadd.3-(3,3-dimethylureido)propyl, .Iaddend.2-(3-methylureido)ethyl, 3-(3-methylureido)propyl, 2-ureidoethyl, 3-ureidopropyl, 2-(N,N-dimethylcarbamoyloxy)ethyl, 3-(N,N-dimethylcarbamoyloxy)propyl, 2-(N-methylcarbamoyloxy)ethyl, 3-(N-methylcarbamoyloxy)propyl, 2-(carbamoyloxy)ethyl, 3-(carbamoyloxy)propyl, 2-(1,3,3-trimethylureido)ethyl, .[.3-1,3,3-trimethylureido)propyl,.]. .Iadd.3-(1,3,3-trimethylureido)propyl, .Iaddend.2-(isopropoxycarbonylamino)ethyl, 3-(isopropoxycarbonylamino)propyl, 2-(isobutoxycarbonylamino)ethyl, 3-(isobutoxycarbonylamino)propyl, 2-(t-butoxycarbonylamino)ethyl or 3-(t-butoxycarbonylamino)propyl; 6) C.sub.2-3alkylX.sup.5R.sup.27 (wherein R.sup.27 is C.sub.1-2alkyl and X.sup.5 is --S--, --SO--, --SO.sub.2--, --SO.sub.2NR.sup.30-- .[.or --NR.sup.31 SO.sub.2--.]. .Iadd.or --NR.sup.31SO.sub.2--).Iaddend.; and 7) C.sub.2-3alkyX.sup.6C.sub.2-3alkylR.sup.33 (wherein X.sup.6 is as defined in claim 1 and R.sup.33 represents a group selected from morpholino, 2-oxopyrrolidin-1-yl, pyrrolidin-1-yl, piperidino, piperazin-1-yl and 4-methylpiperazin-1-yl). 7. A quinazoline derivative of the formula 1a: ##STR00029## wherein: R.sup.1a is hydrogen or methoxy; R.sup.2a is hydrogen; the phenyl group bearing (R.sup.3a).sub.ma is the 4-chloro-2-fluorophenyl group or the 4-bromo-2-fluorophenyl group; X.sup.1a is --O--; R.sup.4a is selected from one of the following nine groups: 1) C.sub.1-4alkylR.sup.7a (wherein R.sup.7a is a group selected from 1,3-dioxolan-2-yl, 1,3-dioxan-2-yl, 1,3-dithiolan-2-yl, 1,3-dithian-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl and piperazin-2-yl which group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.2-3alkanoyl and C.sub.1-3alkoxycarbonyl) or C.sub.2-4alkylR.sup.8a (wherein R.sup.8a is a group selected from imidazolidin-1-yl, pyrrolidin-1-yl and thiomorpholino which group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.2-3alkanoyl and C.sub.1-3alkoxycarbonyl); 2) 1-R.sup.9aprop-1-en-3-yl, 1-R.sup.9abut-2-en-4-yl, 1-R.sup.9abut-1-en-3-yl, 1-R.sup.9apent-2-en-4-yl or 2-R.sup.9apent-3-en-5-yl (wherein R.sup.9a is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group is linked to the alkenyl group through a carbon atom and which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.2-3alkanoyl and C.sub.1-3alkoxycarbonyl) or 1-R.sup.10abut-2-en-4-yl, 1-R.sup.10apent-2-en-4-yl or 2-R.sup.10apent-3-en-5-yl (wherein R.sup.10a is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, of which one is N and the other is selected independently from O, S and N, which heterocyclic group is linked to the alkenyl group through a nitrogen atom and which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbomoyl, N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.1-3alkanoyl and C.sub.1-3alkoxycarbonyl); 3) 1-R.sup.11aprop-1-yn-3-yl, 1-R.sup.11abut-2-yn-4-yl, 1-R.sup.11abut-1-yn-3-yl, 1-R.sup.11apent-2-yn-4-yl or 2-R.sup.11apent-3-yn-5-yl (wherein R.sup.11a is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group is linked to the alkynyl group through a carbon atom and which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.2-3alkanoyl and C.sub.1-3alkoxycarbonyl) or 1-R.sup.12abut-2-yn-4-yl, .[.1-.sup.12apent-2-yn-4-yl.]. .Iadd.1-R.sup.12apent-2-yn-4-yl .Iaddend.or 2-R.sup.12apent-3-yn-5-yl (wherein R.sup.12a is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, of which one is N and the other is selected independently from O, S and N, which heterocyclic group is linked to the alkynyl group through a nitrogen atom and which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, .[.carbarmoyl,.]. .Iadd.carbamoyl, .Iaddend.C.sub.1-3alkylcarbamoyl, .[.N,N-di(C.sub.1-3alkyl)carbarmoyl, C.sub.1-3alkanoyl.]. .Iadd.N,N-di(C.sub.1-3alkyl)carbamoyl, C.sub.2-3alkanoyl .Iaddend.and C.sub.1-3alkoxycarbonyl); 4) C.sub.2-3alkylX.sup.2aC.sub.1-3alkylX.sup.3aR.sup.13a (wherein X.sup.2a and X.sup.3a which may be the same or different each represents, --O--, --S--, --SO--, --SO.sub.2--, --NR.sup.14aCO--, or --NR.sup.15a-- (wherein R.sup.14a and R.sup.15a each independently represents hydrogen, C.sub.1-2alkyl or C.sub.1-2alkoxyethyl) and R.sup.13a represents hydrogen or C.sub.1-3alkyl); 5) .[.C2-3alkylX.sup.4aCOR.sup.16a.]. .Iadd.C.sub.2-3alkylX.sup.4aCOR.sup.16a .Iaddend.(wherein X.sup.4a represents --O-- or --NR.sup.17a--(wherein R.sup.17a represents hydrogen, C.sub.1-3alkyl or C.sub.1-2alkoxyethyl) and R.sup.16a represents --NR.sup.18aR.sup.19a or --OR.sup.20a (wherein R.sup.18a, R.sup.19a and R.sup.20a which may be the same or different each represents hydrogen, C.sub.1-4alkyl or C.sub.1-2alkoxyethyl)); 6) C.sub.2-3alkylX.sup.5aR.sup.21a (wherein X.sup.5a represents carbonyl, --O--, --S--, --SO--, --SO.sub.2--, --NR.sup.22aCO--, --NR.sup.23aSO.sub.2--, or --NR.sup.24a-- (wherein R.sup.22a, R.sup.23a and .[.R.sup.23a each independently.]. .Iadd.R.sup.24a each independently .Iaddend.represents hydrogen, C.sub.1-2alkyl or C.sub.1-2alkoxyethyl) and R.sup.21a represents a group selected from cyclopentyl, cyclohexyl, pyrrolidinyl and piperidinyl which group is linked to X.sup.5a through a carbon atom and which group may carry one substituent selected from oxo, hydroxy, halogeno, C.sub.1-2alkyl, C.sub.1-2hydroxyalkyl, C.sub.1-2alkoxy, carbamoyl, C.sub.1-2alkylcarbamoyl, N,N-di(C.sub.1-2alkyl)carbamoyl, acetyl and C.sub.1-2alkoxycarbonyl or R.sup.21a is C.sub.1-3alkyl with .[.that proviso.]. .Iadd.the proviso .Iaddend.that when R.sup.21a is C.sub.1-3alkyl, X.sup.5a is --S--, --SO--, --SO.sub.2-- or --NR.sup.23aSO.sub.2--); 7) C.sub.2-3alkylX.sup.6aC.sub.2-3alkylR.sup.25a (wherein X.sup.6a represents --O--, --S--, --SO--, --SO.sub.2--, --NR.sup.26aCO--, --NR.sup.27aSO.sub.2-- or --NR.sup.28a-(wherein R.sup.26a, R.sup.27a and R.sup.28a each independently represents hydrogen, C.sub.1-2alkyl or C.sub.1-2alkoxyethyl) and R.sup.25a represents a 5 or 6 membered saturated heterocyclic group with one or two heteratoms selected independently from O, S and N, which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3hydroxyalkyl, C.sub.1-3alkoxy, carbamoyl, C.sub.1-3alkylcarbamoyl, .[.N,N-di(C.sub.1-3alkyl)cabamoyl,.]. .Iadd.N,N-di(C.sub.1-3alkyl)carbamoyl, .Iaddend.C.sub.2-3alkanoyl, and .[.C1-3allkoxycarbonyl);.]. .Iadd.C.sub.1-3alkoxycarbonyl);.Iaddend. 8) C.sub.2-3alkylR.sup.29a (wherein R.sup.29a is .[.piperizin-1-yl.]. .Iadd.piperazin-1-yl .Iaddend.which bears at least one substituent selected from acetyl, C.sub.1-2alkoxycarbonyl, C.sub.1-2hydroxyalkyl and CONR.sup.30aR.sup.31a (wherein R.sup.30a and R.sup.31a each independently represents hydrogen .[.or C.sub.1-2alkyl).]. .Iadd.or C.sub.1-2alkyl)).Iaddend.; and 9) C.sub.2-3alkylR.sup.33a (wherein R.sup.33a is morpholino which bears at least one and optionally two substituents selected from oxo, C.sub.1-2alkyl, C.sub.1-2hydroxyalkyl, carbamoyl, C.sub.1-2alkylcarbamoyl, N,N-di(C.sub.1-2alkyl)carbamoyl, acetyl and C.sub.1-2alkoxycarbonyl); or a salt thereof. .[.8. A quinazoline derivative as claimed in claim 1 selected from: 4-(4-chloro-2-fluoroanilino)-7-(1,3-dioxolan-2-ylmethoxy)-6-methoxyquinzo- line; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-morpholinobut-2-en-1-ylo- xy)quinazoline; (E)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-morpholinobut-2-en-1-ylox- y)-quinazoline; 4-(4-chloro-2-fluoroanilino)-7-(3-(2,6-dimethylmorpholino)propoxy)-6-meth- oxyquinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-([N-methyl-N-methylsulphonyl]- amino)-propoxy)quinazoline; 7-(2-[N-tert-butoxycarbonylamino]ethoxy)-4-(4-chloro-2-fluoroanilino)-6-m- ethoxyquinazoline; 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(3-([N-methyl-N-methylsulphonyl]a- mino)-propoxy)quinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-2-(2-oxoimidazolidin-1-yl)ethoxy- )quinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(3-oxomorpholino)ethoxy)quina- zoline; 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-(3-oxomorpholino)ethoxy- )quinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-thiomorpholinoethoxy)quinazol- ine; (S)-4-(4-bromo-2-fluoroanilino)-7-(3-(2-carbamoylpyrrolidin-1-yl)prop- oxy-6-methoxyquinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-(2-oxopyrrolidin-1-yl)propoxy- )quinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-oxopyrrolidin-1-yl)ethoxy)- -quinazoline; (S)-7-(3-(2-carbamoylpyrrolidin-1-yl)propoxy)-4-(4-chloro-2-fluoroanilino- )-6-methoxyquinazoline, 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-morpholinoethoxy)ethoxy)-q- uinazoline; and 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(3-(2-oxopyrrolidin-1-yl)propoxy)- -quinazoline; and salts thereof..]. .[.9. A quinazoline derivative as claimed in claim 1 selected from: 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)quina- zoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-3-yl)-- methoxyquinazoline; 4-(4-bromo-2-fluoroanilino)-7-3-(1,1-dixothiomorpholino)propoxy)-6-methox- yquinazoline; 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)quinaz- oline, 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-2-pyrrolidin-1-ylethoxy- )ethoxy)-quinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-[4-methylpiperazin-1-yl]et- hoxy)-ethoxy)quinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-([N-methyl-N-methoxyacetyl]am- ino)-ethoxy)quinazoline; and 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-2-oxopyrrolidin-1-yl)ethoxy)qu- inazoline; and salts thereof..]. .[.10. A quinazoline derivative as claimed in claim 1 selected from: (E)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-(pyrrolidin-1-yl)but-2-en- -1-yloxy)-quinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-(methylsulphonyl)propoxy)quin- azoline; (S)-4-4-chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-3-- yl)-methoxyquinazoline; and (R)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-3-yl)-met- hoxyquinazoline; and salts thereof..]. .[.11. A quinazoline derivative as claimed in claim 1 selected from: 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-(methylsulphonyl)propoxy)quin- azoline; and salts thereof..]. 12. A quinazoline derivative as claimed in .[.any one of claims 1 and 7-11.]. .Iadd.claim 1 or claim 7 .Iaddend.in the form of pharmaceutically acceptable salt. 13. A quinazoline derivative as claimed in claim 1 or claim 2 wherein R.sup.1 represents methoxy. 14. A quinazoline derivative as claimed in claim 1 or claim 2 wherein m is 2. 15. A quinazoline derivative as claimed in claim 1 or claim 2 wherein the phenyl group bearing (R.sup.3)m is the 4-chloro-2-fluorophenyl group or the 4-bromo-2-fluorophenyl group. 16. A quinazoline derivative as claimed in claim 1 or claim 2 wherein R.sup.4 is selected from one of the following six groups: 1) C.sub.1-3alkylR.sup.12 (wherein R.sup.12 is 1,3-dioxolan-2-yl, 1,3-dioxan-2-yl, 1,3dithiolan-2-yl, 1,3-dithian-2-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, 1-methylpiperidin-2-yl, 1-methylpiperidin-3-yl, 1-methylpiperidin-4- yl, 1-methylpyrrolidin-2-yl, 1-methylpyrrolidin-3-yl, piperazin-2-yl, 1-methylpiperazine-2-yl, 4-methylpiperazin-2-yl, 1,4-dimethylpiperazin-2-yl, morpholin-2-yl, morpholin-3-yl, 4-methylmorpholin-2-yl or 4-methylmorpholin-3- yl) or C.sub.2-3alkylR.sup.45 (wherein R.sup.45 is pyrrolidin-1-yl, thiomorpholino, 1,1- dioxothiomorpholino, 2-oxopyrrolidin-1-yl, 2-(N-methylcarbamoyl)pyrrolidin-1-yl, 2-(N,N-dimethylcarbamoyl)pyrrolidin-1-yl, 2-carbamoylpyrrolidin-1yl, 2- oxoimidazolidin-1-yl or 3-methyl-2-oxoimidazolidin-1-yl); 2) 1-R.sup.50but-2-en-4-yl (wherein R.sup.50 is 2-oxoimidazolidin-1-yl, 1,3-dioxolan-2-yl, 1,3- dioxan-2-yl, 1,3-dithiolan-2-yl, 1,3-dithian-2-yl, piperidin-4-yl, 1-methylpiperidin-4- yl, pyrrolidin-1-yl, 1-methylpyrrolidin-3-yl, piperazin-1-yl, morpholino, thiomorpholino, 4-methylpiperazin-1-yl, piperidino or 3-methyl-2-oxoimidazolidin- 1-yl); 3) 1-R.sup.51but-2-yn-4-yl (wherein R.sup.51 is 2-oxoimidazolidin-1-yl, 1,3-dioxolan-2-yl, 1,3- dioxan-2-yl, 1,3-dithiolan-2-yl, 1,3-dithian-2-yl, piperidin-4-yl, 1-methylpiperidin-4- yl, pyrrolidin-1-yl, 1-methylpyrrolidin-3-yl, piperazin-1-yl, morpholino, thiomorpholino, 4-methylpiperazin-1-yl, piperidino or 3-methyl-2-oxoimidazolidin- 1-yl); 4) C.sub.2-3alkylX.sup.2C.sub.1-3alkylX.sup.3R.sup.16 (wherein X.sup.2 and X.sup.3 are as defined in claim 17 and R.sup.16 represents hydrogen or C.sub.1-3alkyl); 5) C.sub.2-3alkylX.sup.5R.sup.27 (wherein R.sup.27 is C.sub.1-2 alkyl and X.sup.5 is -S-, -SO-, -SO.sub.2-, -SO.sub.2NR.sup.30-or- NR.sup.31SO.sub.2-(wherein R.sup.30 and R.sup.31 are as defined in claim 1)); and 6) C.sub.2-3alkylX.sup.6C.sub.2-3alkylR.sup.33 (wherein X.sup.6 is as defined in claim 1 and R.sup.33 represents a group selected from pyrrolidin-1-yl, 4-methylpiperazin-1-yl and morpholino). 17. A quinazoline derivative of the formula I: ##STR00030## wherein: m is an integer from 1 to 2; R.sup.1 represents hydrogen, hydroxy, halogeno, .[.nitro,.]. trifuloromethyl, .[.eyano,.]. .Iadd.cyano, .Iaddend.C.sub.1-3alkyl, C.sub.1-3alkoxy, C.sub.1-3alkylthio, or -NR.sup.5R.sup.6 (wherein R.sup.5and R.sup.6, which may be the same or different, each represents hydrogen or C.sub.1-3alkyl); .[.R.sub.2.]. .Iadd.R.sup.2 .Iaddend.represents hydrogen, hydroxy, .[.halageno,.]. .Iadd.halogeno, .Iaddend.methoxy.[.,.]. .Iadd.or .Iaddend.amino.[.or nitro.].; .[.R.sub.3.]. .Iadd.R.sup.3 .Iaddend.represents hydroxy, halogeno, C.sub.1-3alkyl, C.sub.1-3alkoxy, C.sub.1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X.sup.1 represents -O-; R.sup.4 is selected from one of the following seven groups: 1) C.sub.1-5alkylR.sup.12 (wherein R.sup.12 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group is linked to C.sub.1-5alkyl through a carbon atom and which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl and C.sub.1-4alkoxy) or C.sub.1-5alkylR.sup.13 (wherein R.sup.13 is a group selected from pyrrolidin-1-yl, imidazolidin-1-yl and thiomorpholino, which group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl and C.sub.1-4alkoxy); 2) .[.C.sub.2-5alkenylR.sup.14.]. .Iadd.C.sub.2-5alkenylR.sup.14 .Iaddend.(wherein R.sup.14 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-4alkyl, .[.C.sub.1-4hydroyalkyl.]. .Iadd.C.sub.1-4hydroxyalkyl .Iaddend.and C.sub.1-4alkoxy); 3) C.sub.2-5alkynylR.sup.15 (wherein R.sup.15 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or two substituents selected from oxo, hydroxy halogeno, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl and C.sub.1-4alkoxy); 4) C.sub.1-5alkylX.sup.2C.sub.1-5alkylX.sup.3R.sup.16 (wherein X.sup.2 and X.sup.3 which may be the same or different are each -O-, -S-, -SO-, -SO.sub.2-, -NR.sup.17CO-, -CONR.sup.18-, .[..sup.-SO.sub.2NR.sup.19-, -NR.sup.20SO.sub.2-.]. .Iadd.--SO.sub.2NR.sup.19--, --NR.sup.20SO.sub.2-- .Iaddend.or -NR.sup.21- (wherein R.sup.17, R.sup.18, R.sup.19, R.sup.20 and R.sup.21 each .[.independetly.]. .Iadd.independently .Iaddend.represents hydrogen, C.sub.1-3alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl) and R.sup.16 represents hydrogen or C.sub.1-3alkyl); 5) C.sub.1-5alkylX.sup.4COR.sup.22 (wherein X.sup.4 represents -O- or -NR.sup.23-(wherein R.sup.23 represents hydrogen, C.sub.1-3alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl) and R.sup.22 represents -NR.sup.24R.sup.25 or -OR.sup.26 (wherein R.sup.24, R.sup.25 and R.sup.26 which may be the same or different each represents hydrogen, C.sub.1-4alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl)); 6) C.sub.1-5alkylX.sup.5R.sup.27 (wherein X.sup.5 represents -O-, -S-, -SO.sub.2-, -OCO-, -NR.sup.28CO-, -CONR.sup.29-, -SO.sub.2NR.sup.30-, -NR.sup.31SO.sub.2- or -NR.sup.32-(wherein R.sup.28, R.sup.29, R.sup.30, R.sup.31 and R.sup.32 each independently represents hydrogen, C.sub.1-3alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl) and R.sup.27 represents cyclopentyl, cyclohexyl or a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which cyclopentyl, cyclohexyl or heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl .[.and C.sub.1-4alkoxy.]. .Iadd.and C.sub.1-4alkoxy).Iaddend.; and 7) C.sub.1-3alkoxyC.sub.2-4alkyl or C.sub.1-4alkyl; with the proviso that when R.sup.4 is selected from group 7) .[.R.sup.1 and/or R.sup.2 is/are nitro or.]. at least one R.sup.3 is C.sub.1-3alkanoyloxy; and salts thereof. 18. A quinazoline derivative as claimed in claim 17 wherein R.sup.1 represents methoxy. 19. A quinazoline derivative as claimed in 17 or claim 18 wherein R.sup.2 represents hydrogen. 20. A quinazoline derivative as claimed in claim 17 or claim 18 wherein the phenyl group bearing (R.sup.3)m is of the formula II: ##STR00031## wherein: R.sup.a represents hydrogen, methyl, fluoro or chloro; R.sup.b represents hydrogen, methyl, methoxy, bromo, fluoro or chloro; R.sup.c represents hydrogen or hydroxy; R.sup.d represents hydrogen, fluoro or chloro. 21. A process for the preparation of a quinazoline derivative of formula I or salt thereof (as defined in claim 1) which comprises: (a) the reaction of a compound of the formula III: ##STR00032## (wherein R.sup.1, R.sup.2, X.sup.1 and R.sup.4 are as defined in claim 1 and L.sup.1 is a displaceble moiety), with a compound of the formula IV: ##STR00033## (wherein R.sup.3 and m are as defined in claim 1) whereby to obtain compounds of the formula I and salts thereof; (b) for the .[.preperation.]. .Iadd.preparation .Iaddend.of compounds of formula I and salts thereof in which the group of formula IIa: ##STR00034## (wherein R.sup.3 and m are as defined in claim 1) represents a phenyl group carrying one or more hydroxy groups, the deprotection of a compound of formula V: ##STR00035## (wherein X.sup.1, m, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined in claim 1, P represents a phenolic hydroxy protecting group and p1 is an integer from 1 to 5 equal to the number of protected hydroxy groups and such that m-p1 is equal to the number of R.sup.3 substituents which are not protected hydroxy); (c) for the preparation of those compounds of formula I and salts thereof wherein the substituent X.sup.1 is --O--, the reaction of a compound of the formula VI: ##STR00036## (wherein X.sup.1, R.sup.1, R.sup.2 and R.sup.3 are as defined in claim 1) with a compound of formula VII: R.sup.4--L.sup.1 (VII) (wherein .[.R.sup.14.]. .Iadd.R.sup.4 .Iaddend.is as defined .[.im.]. .Iadd.in .Iaddend.claim 1 and L.sup.1 is as defined herein); (d) the reaction of a compound of the formula VII: ##STR00037## with a compound of the formula IX: R.sup.4--X.sup.1--H (IX) (wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, m and X.sup.1 are as defined in claim 1 and L.sup.1 is as defined herein); (e) for the preparation of compounds of formula I and salts thereof wherein R.sup.4 is C.sub.1-5alkylR.sup.53, wherein R.sup.53 is selected from one of the following three groups: 1) X.sup.7R.sup.27 (wherein X.sup.7 represents --O--, --S--, --SO.sub.2--, --NR.sup.54CO--, --NR.sup.55SO.sub.2-- or --NR.sup.56-- (wherein R.sup.54, R.sup.55 and R.sup.56 each independently represents hydrogen, C.sub.1-3alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl) and R.sup.27 is as defined in claim 1); 2) X.sup.8C.sub.1-5alkylX.sup.3R.sup.16 (wherein X.sup.8 represents --O--, --S--, .[.--SO.sub.12--,.]. .Iadd.--SO.sub.2--, .Iaddend.--NR.sup.57CO--, --NR.sup.58SO.sub.2-- or --NR.sup.59-- (wherein R.sup.57, R.sup.58 and R.sup.59 each independently represents hydrogen, C.sub.1-3alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl) and X.sup.3 and R.sup.16 are as defined in claim 1); and 3) X.sup.9C.sub.1-5alkylR.sup.33 (wherein X.sup.9 represents --O--, --S--, --SO.sub.2--, --NR.sup.60CO--NR.sup.61SO.sub.2-- or --NR.sup.62-- (wherein R.sup.60, R.sup.61 and R.sup.62 each independently .[.represent.]. .Iadd.represents .Iaddend.hydrogen, C.sub.1-3alkyl or C.sub.1-3alkoxyC.sub.2-3alkyl) and R.sup.33 is as defined in claim 1); the reaction of a compound of the formula X: ##STR00038## (wherein X.sup.1, R.sup.1, R.sup.2, R.sup.3 and m are as defined in claim 1, L.sup.1 is as defined herein and R.sup.63 is C.sub.1-5alkyl) with a compound of the formula XI: R.sup.53--H (XI) (wherein R.sup.53 is as defined herein) to give a compound of the formula I; (f) for the preparation of compounds of the formula I wherein R.sup.4 is C.sub.2-5alkylR.sup.45, (wherein R.sup.45 is a group selected from imidazolidin-1-yl, pyrrolidin-1-yl and thiomorpholino, which group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-4alkyl, C.sub.1-4hydroxyalkyl, C.sub.1-4alkoxy, carbamoyl, C.sub.1-4alkylcarbamoyl, N,N-di(C.sub.1-4alkyl)carbamoyl, C.sub.1-4alkanoyl and C.sub.1-4alkoxycarbonyl), the reaction of a compound of formula X (wherein R.sup.63 is C.sub.2-5alkyl) with a compound of the formula XIa: R.sup.45--H (XIa) (wherein R.sup.45 is as defined herein) to give a compound of the formula I; (g) for the preparation of those compounds of the formula I and salts thereof wherein the substituent R.sup.1 is represented by --NR.sup.5R.sup.6 where one or both of R.sup.5 and R.sup.6 are C.sub.1-3alkyl, the reaction of compounds of formula I wherein the substituent R.sup.1 is an amino group with an alkylating agent; (h) for the prepation of compounds of formula I and salts thereof wherein one or more of the substituents R.sup.1, R.sup.2 or R.sup.3 is an amino group, the reduction of a corresponding compound .[.of formula I.]. wherein the substituent(s) at the corresponding position(s) of the quinazoline and/or aniline ring is/are a nitro group(s): and when a pharmaceutically acceptable salt of a quinazoline derivative of formula I is required, reaction of the compound obtained with an acid or base whereby to obtain the desired pharmaceutically acceptable salt. 22. A pharmaceutical composition which comprises as active ingredient a compound of formula I as defined in .[.any one of claims 1 and 7-11.]. .Iadd.claim 1 or claim 7 .Iaddend.or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable excipient or carrier. .[.23. A method for producing an antiangiogenic and/or vascular permeability reducing effect in a warm-blooded animal in need of such treatment which comprises administering to said animal an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof as defined in any one of claims 1 and 7-11..].