Details for Patent: 6,414,148

Title:	Quinazoline derivatives and pharmaceutical compositions containing them
Abstract:	The invention relates to quinazoline derivatives of formula (1) ##STR1## wherein m is an integer from 1 to 2; R.sup.1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C.sub.1-3 alkyl, C.sub.1-3 alkoxy, C.sub.1-3 alkylthio, or --NR.sup.5 R.sup.6 (wherein R.sup.5 and R.sup.6, which may be the same or different, each represents hydrogen or C.sub.1-3 alkyl); R.sup.2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R.sup.3 represents hydroxy, halogeno, C.sub.1-3 alkyl, C.sub.1-3 alkoxy, C.sub.1-3 alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X.sup.1 represents --O--, --CH.sub.2 --, --S--, --SO--, --SO.sub.2 --, --NR.sup.7 CO--, --CONR.sup.8 --, --SO.sub.2 NR.sup.9 --, --NR.sup.10 SO.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.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl); 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:	Zeneca Limited (London, GB) Zeneca Pharma S.A. (Cedex, FR)
Filing Date:	Mar 25, 1999
Application Number:	09/269,595
Claims:	1. A quinazoline derivative of the formula I: ##STR27## wherein: m is an integer from 1 to 2; R.sup.1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C.sub.1-3 alkyl, C.sub.1-3 alkoxy, C.sub.1-3 alkylthio, or --NR.sup.5 R.sup.6 (wherein R.sup.5 and R.sup.6, which may be the same or different, each represents hydrogen or C.sub.1-3 alkyl); R.sup.2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R.sup.3 represents hydroxy, halogeno, C.sub.1-3 alkyl, C.sub.1-3 alkoxy, C.sub.1-3 alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X.sup.1 represents --O--, R.sup.4 is selected from one of the following eleven groups: 1) C.sub.1-5 alkylR.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.1-5 alkyl through a carbon atom and which heterocyclic group may bear one or two substituent selected from oxo, hydroxy, halogeno, C.sub.1-4 alkyl, C.sub.1-4 hydroxyalkyl, C.sub.1-4 alkoxy, carbamoyl, C.sub.1-4 alkylcarbamoyl, N,N-di(C.sub.1-4 alkyl)carbamoyl, C.sub.1-4 alkanoyl and C.sub.1-4 alkoxycarbonyl) or C.sub.1-5 alkylR.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 selected from oxo, hydroxy, halogeno, C.sub.1-4 alkyl, C.sub.1-4 hydroxyalkyl, C.sub.1-4 alkoxy, carbamoyl, C.sub.1-4 alkylcarbamoyl, N,N-di(C.sub.1-4 alkyl)carbamoyl, C.sub.1-4 alkanoyl and C.sub.1-4 alkoxycarbonyl); 2) C.sub.2-5 alkenylR.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 selected from oxo, hydroxy, halogeno, C.sub.1-4 alkyl, C.sub.1-4 hydroxyalkyl, C.sub.1-4 alkoxy, carbamoyl, C.sub.1-4 alkylcarbamoyl, N,N-di(C.sub.1-4 alkyl)carbamoyl, C.sub.1-4 alkanoyl and C.sub.1-4 alkoxycarbonyl); 3) C.sub.3-5 alkynylR.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 selected from oxo, hydroxy, halogeno, C.sub.1-4 alkyl, C.sub.1-4 hydroxyalkyl, C.sub.1-4 alkoxy, carbamoyl, C.sub.1-4 alkylcarbamoyl, N,N-di(C.sub.1-4 alkyl)carbamoyl, C.sub.1-4 alkanoyl and C.sub.1-4 alkoxycarbonyl); 4) C.sub.1-5 alkylX.sup.2 C.sub.1-5 alkylX.sup.3 R.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.17 CO--, --CONR.sup.18 --, --SO.sub.2 NR.sup.19 --, --NR.sup.20 SO.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.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl) and R.sup.16 represents hydrogen or C.sub.1-3 alkyl); 5) C.sub.1-5 alkylX.sup.4 COR.sup.22 (wherein X.sup.4 represents --O-- or --NR.sup.23 -- (wherein R.sup.23 represents hydrogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl) and R.sup.22 represents --NR.sup.24 R.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.1-4 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl)); 6) C.sub.1-5 alkylX.sup.5 R.sup.27 (wherein X.sup.5 represents --O--, --S--, --SO--, --SO.sub.2 --, --OCO--, --NR.sup.28 CO--, --CONR.sup.29 --, --SO.sub.2 NR.sup.30 --, --NR.sup.31 SO.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.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl) 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 selected from oxo, hydroxy, halogeno, C.sub.1-4 alkyl, C.sub.1-4 hydroxyalkyl, C.sub.1-4 alkoxy, carbamoyl, C.sub.1-4 alkylcarbamoyl, N,N-di(C.sub.1-4 alkyl)carbamoyl, C.sub.1-4 alkanoyl and C.sub.1-4 alkoxycarbonyl or R.sup.27 is C.sub.1-3 allyl with the proviso that when R.sup.27 is C.sub.1-3 alkyl, X.sup.5 is --S--, --SO--, --SO.sub.2 --, --SO.sub.2 NR.sup.30 -- or --NR.sup.31 SO.sub.2 --; 7) C.sub.1-3 alkoxyC.sub.2-4 alkyl or C.sub.1-4 alkyl; 8) C.sub.1-5 alkylX.sup.6 C.sub.1-5 alkylR.sup.33 (wherein X.sup.6 represents --O--, --S--, --SO--, --SO.sub.2 --, --NR.sup.34 CO--, --CONR.sup.35 --, --SO.sub.2 NR.sup.36 --, --NR.sup.37 SO.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.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl) 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 selected from oxo, hydroxy, halogeno, C.sub.1-4 alkyl), C.sub.1-4 hydroxyalkyl, C.sub.1-4 alkoxy, carbamoyl, C.sub.1-4 alkylcarbamoyl, N,N-di(C.sub.1-4 alkyl)carbamoyl, C.sub.1-4 alkanoyl and C.sub.1-4 alkoxycarbonyl); 9) R.sup.39 (wherein R.sup.39 is a group selected from pyrrolidin-3-yl, piperidine-3-yl and piperidine-4-yl which group may bear one or two substituent selected from oxo, hydroxy, halogeno, C.sub.1-4 alkyl, C.sub.1-4 hydroxyalkyl, C.sub.1-4 alkoxy, carbamoyl, C.sub.1-4 alkylcarbamoyl, N,N-di(C.sub.1-4 alkyl)carbamoyl, C.sub.1-4 alkanoyl and C.sub.1-4 alkoxycarbonyl); 10) C.sub.1-5 alkylR.sup.40 (wherein R.sup.40 is piperazin-1-yl which bears at least one substituent selected from C.sub.1-4 alkanoyl, C.sub.1-4 alkoxycarbonyl, C.sub.1-4 hydroxyalkyl and --CONR.sup.41 R.sup.42 (wherein R.sup.41 and R.sup.42 each independently represents hydrogen or C.sub.1-4 alkyl); and 11) C.sub.1-5 alkylR.sup.44 (wherein R.sup.44 is morpholino which bears at least one and optionally two substituent selected from oxo, C.sub.1-4 alkyl, C.sub.1-4 hydroxyalkyl, carbamoyl, C.sub.1-4 alkylcarbamoyl, N,N-di(C.sub.1-4 alkyl)carbamoyl, C.sub.1-4 alkanoyl and C.sub.1-4 alkoxycarbonyl); 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.1-3 alkanoyloxy; 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: ##STR28## 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.1-4 alkylR.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, 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.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)carbamoyl, C.sub.2-3 alkanoyl and C.sub.1-3 alkoxycarbonyl) or C.sub.2-4 alkylR.sup.45 (wherein R.sup.45 is a group selected from imidazolidine-1-yl, pyrrolidin-1-yl and thiomorpholino which group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)carbamoyl, C.sub.2-3 alkanoyl and C.sub.1-3 alkoxycarbonyl); 2) 1-R.sup.46 prop-1-en-3-yl, 1-R.sup.46 but-2-en-4-yl, 1-but-1-en-3-yl, 1-R.sup.46 pent-2-en-4-yl or 2-R.sup.46 pent-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 selected from oxo, hydroxy, halogeno, C.sub.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)carbamoyl, C.sub.2-3 alkanoyl and C.sub.1-3 alkoxycarbonyl) or 1-R.sup.47 but-2-en-4-yl, 1-R.sup.47 pent-2-en-4-yl or 2-R.sup.47 pent-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.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)carbamoyl, C.sub.2-3 alkanoyl and C.sub.1-3 alkoxycarbonyl); 3) 1-R.sup.48 prop-1-yn-3-yl, 1-R.sup.48 but-2-yn-4-yl, 1-R.sup.48 but-1-yn-3-yl, 1-R.sup.48 pent-2-yn-4-yl or 2-R.sup.48 pent-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.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)carbamoyl, C.sub.2-3 alkanoyl and C.sub.1-3 alkoxycarbonyl) or 1-R.sup.49 but-2-yn-4-yl, 1-R.sup.49 pent-2-yn-4-yl or 2-R.sup.49 pent-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.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkylcarbamoyl, C.sub.2-3 alkanoyl and C.sub.1-3 alkoxycarbonyl); 4) C.sub.2-3 alkylX.sup.2 C.sub.1-3 alkylX.sup.3 R.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.1-3 alkyl); 5) C.sub.2-3 alkylX.sup.4 COR.sup.22 (wherein X.sup.4 is as defined in claim 1 and R.sup.22 represents --NR.sup.24 R.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.1-4 alkyl or C.sub.1-2 alkoxyethyl)); 6) C.sub.2-3 alkylX.sup.5 R.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.1-2 alkyl, C.sub.1-2 hydroxyalkyl, C.sub.1-2 alkoxy, carbamoyl, C.sub.1-2 alkylcarbamoyl, N,N-di(C.sub.1-2 alkyl)carbamoyl, acetyl and C.sub.1-2 alkoxycarbonyl or R.sup.27 is C.sub.1-3 alkyl with the proviso that when R.sup.27 is C.sub.1-3 alkyl, X.sup.5 is --S--, --SO--, --SO.sub.2 --, --SO.sub.2 N.sup.30 -- or --NR.sup.31 SO.sub.2 --); 7) C.sub.2-3 alkylX.sup.6 C.sub.2-3 alkyl.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 selected from oxo, hydroxy, halogeno, C.sub.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)carbamoyl, C.sub.2-3 alkanoyl, and C.sub.1-3 alkoxycarbonyl); 8) C.sub.2-3 alkylR.sup.40 is piperazin-1-yl which bears at least one substituent selected from acetyl, C.sub.1-2 alkoxycarbonyl, C.sub.1-2 hydroxyalkyl and CONR.sup.41 R.sup.42 (wherein R.sup.41 and R.sup.42 each independently represents hydrogen or C.sub.1-2 alky); and 9) C.sub.2-3 alkylR.sup.44 is morpholino which bears at least one and optionally two substituents selected from oxo, C.sub.1-2 alky, C.sub.1-2 hydroxyalkyl, carbamoyl, C.sub.1-2 alkylcarbamoyl, N,N-di(C.sub.1-2 alkyl)carbamoyl, acaetyl and C.sub.1-2 alkoxycarbonyl). 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 (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.1-2 alkyl, C.sub.1-2 hydroxyalkyl, C.sub.1-2 alkoxy, carbamoyl, C.sub.1-2 alkylcarbamoyl, N,N-di(C.sub.1-2 alkyl)carbamoyl, acetyl and C.sub.1-2 alkoxycarbonyl) or C.sub.2-3 alkylR.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.1-2 alkyl, C.sub.1-2 hydroxyalkyl, C.sub.1-2 alkoxy, carbamoyl, C.sub.1-2 alkylkcarbamoyl, N,N-di(C.sub.1-2 alkyl)carbamoyl, acetyl and C.sub.1-2 alkoxycarbonyl); 2) 1-R.sup.50 but-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.1-2 alkyl, C.sub.1-2 hydroxyalkyl, C.sub.1-2 alkoxy, carbamoyl, C.sub.1-2 alkylcarbamoyl, N,N-di(C.sub.1-2 alkyl)carbamoyl, acetyl and C.sub.1-2 alkoxycarbonyl). 3) 1-R.sup.51 but-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.1-2 alkyl, C.sub.1-2 hydroxyalkyl, C.sub.1-2 alkoxy, carbamoyl, C.sub.1-2 alkylcarbamoyl, N,N-di(C.sub.1-2 alkyl)carbamoyl, acetyl and C.sub.1-2 alkoxycarbonyl); 4) C.sub.2-3 alkylX.sup.2 C.sub.1-3 alkylX.sup.3 R.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.1-3 alkyl); 5) 2-(3,3-dimethylureido)ethyl, 3-(3,3dimethylureido)propyl, 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, 2-(isopropoxycarbonylamino)ethyl, 3-(isopropoxycarbonylamino)propyl, 2-(isobutoxycarbonylamino)ethyl, 3-(isobutoxycarbonylamino)propyl, 2-(t-butoxycarbonylamino)ethyl or 3-(t-butoxycarbonylamino)propyl; 6) C.sub.2-3 alkylX.sup.5 R.sup.27 (wherein R.sup.27 is C.sub.1-2 alkyl and X.sup.5 is --S--, --SO--, --SO.sub.2 --, --SO.sub.2 NR.sup.30 -- or --NR.sup.31 SO.sub.2 --; and 7) C.sub.2-3 alkyX.sup.6 C.sub.2-3 alkylR.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: ##STR29## 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.1-4 alkylR.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.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)carbamoyl, C.sub.2-3 alkanoyl and C.sub.1-3 alkoxycarbonyl) or C.sub.2-4 alkylR.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.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)carbamoyl, C.sub.2-3 alkanoyl and C.sub.1-3 alkoxycarbonyl); 2) 1-R.sup.9a prop-1-en-3-yl, 1-R.sup.9a but-2-en-4-yl, 1-R.sup.9a but-1-en-3-yl, 1-R.sup.9a pent-2-en-4-yl or 2-R.sup.9a pent-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.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)carbamoyl, C.sub.2-3 alkanoyl and C.sub.1-3 alkoxycarbonyl) or 1-R.sup.10a but-2-en-4-yl, 1-R.sup.10a pent-2-en-4-yl or 2-R.sup.10a pent-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.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbomoyl, N,N-di(C.sub.1-3 alkyl)carbamoyl, C.sub.1-3 alkanoyl and C.sub.1-3 alkoxycarbonyl); 3) 1-R.sup.11a prop-1-yn-3-yl, 1-R.sup.11a but-2-yn-4-yl, 1-R.sup.11a but-1-yn-3-yl, 1-R.sup.11a pent-2-yn-4-yl or 2-R.sup.11a pent-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.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)carbamoyl, C.sub.2-3 alkanoyl and C.sub.1-3 alkoxycarbonyl) or 1-R.sup.12a but-2-yn-4-yl, 1-.sup.12a pent-2-yn-4-yl or 2-R.sup.12a pent-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.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbarmoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)carbarmoyl, C.sub.1-3 alkanoyl and C.sub.1-3 alkoxycarbonyl); 4) C.sub.2-3 alkylX.sup.2a C.sub.1-3 alkylX.sup.3a R.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.14a CO--, or --NR.sup.15a -- (wherein R.sup.14a and R.sup.15a each independently represents hydrogen, C.sub.1-2 alkyl or C.sub.1-2 alkoxyethyl) and R.sup.13a represents hydrogen or C.sub.1-3 alkyl); 5) C2-3alkylX.sup.4a COR.sup.16a (wherein X.sup.4a represents --O-- or --NR.sup.17a --(wherein R.sup.17a represents hydrogen, C.sub.1-3 alkyl or C.sub.1-2 alkoxyethyl) and R.sup.16a represents --NR.sup.18a R.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.1-4 alkyl or C.sub.1-2 alkoxyethyl)); 6) C.sub.2-3 alkylX.sup.5a R.sup.21a (wherein X.sup.5a represents carbonyl, --O--, --S--, --SO--, --SO.sub.2 --, --NR.sup.22a CO--, --NR.sup.23a SO.sub.2 --, or --NR.sup.24a -- (wherein R.sup.22a, R.sup.23a and R.sup.23a each independently represents hydrogen, C.sub.1-2 alkyl or C.sub.1-2 alkoxyethyl) 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.1-2 alkyl, C.sub.1-2 hydroxyalkyl, C.sub.1-2 alkoxy, carbamoyl, C.sub.1-2 alkylcarbamoyl, N,N-di(C.sub.1-2 alkyl)carbamoyl, acetyl and C.sub.1-2 alkoxycarbonyl or R.sup.21a is C.sub.1-3 alkyl with that proviso that when R.sup.21a is C.sub.1-3 alkyl, X.sup.5a is --S--, --SO--, --SO.sub.2 -- or --NR.sup.23a SO.sub.2 --); 7) C.sub.2-3 alkylX.sup.6a C.sub.2-3 alkylR.sup.25a (wherein X.sup.6a represents --O--, --S--, --SO--, --SO.sub.2 --, --NR.sup.26a CO--, --NR.sup.27a SO.sub.2 -- or --NR.sup.28a -(wherein R.sup.26a, R.sup.27a and R.sup.28a each independently represents hydrogen, C.sub.1-2 alkyl or C.sub.1-2 alkoxyethyl) 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.1-3 alkyl, C.sub.1-3 hydroxyalkyl, C.sub.1-3 alkoxy, carbamoyl, C.sub.1-3 alkylcarbamoyl, N,N-di(C.sub.1-3 alkyl)cabamoyl, C.sub.2-3 alkanoyl, and C1-3allkoxycarbonyl); 8) C.sub.2-3 alkylR.sup.29a (wherein R.sup.29a is piperizin-1-yl which bears at least one substituent selected from acetyl, C.sub.1-2 alkoxycarbonyl, C.sub.1-2 hydroxyalkyl and CONR.sup.30a R.sup.31a (wherein R.sup.30a and R.sup.31a each independently represents hydrogen or C.sub.1-2 alkyl); and 9) C.sub.2-3 alkylR.sup.33a (wherein R.sup.33a is morpholino which bears at least one and optionally two substituents selected from oxo, C.sub.1-2 alkyl, C.sub.1-2 hydroxyalkyl, carbamoyl, C.sub.1-2 alkylcarbamoyl, N,N-di(C.sub.1-2 alkyl)carbamoyl, acetyl and C.sub.1-2 alkoxycarbonyl); 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-methoxyquinzoli ne; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-morpholinobut-2-en-1-yloxy)quin azoline; (E)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-morpholinobut-2-en-1-yloxy) -quinazoline; 4-(4-chloro-2-fluoroanilino)-7-(3-(2,6-dimethylmorpholino)propoxy)-6-methox yquinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-([N-methyl-N-methylsulphonyl]am ino)-propoxy)quinazoline; 7-(2-[N-tert-butoxycarbonylamino]ethoxy)-4-(4-chloro-2-fluoroanilino)-6-met hoxyquinazoline; 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(3-([N-methyl-N-methylsulphonyl]ami no)-propoxy)quinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-2-(2-oxoimidazolidin-1-yl)ethoxy)q uinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(3-oxomorpholino)ethoxy)quinazo line; 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-(3-oxomorpholino)ethoxy)quinazol ine; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-thiomorpholinoethoxy)quinazolin e; (S)-4-(4-bromo-2-fluoroanilino)-7-(3-(2-carbamoylpyrrolidin-1-yl)propoxy-6- methoxyquinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-(2-oxopyrrolidin-1-yl)propoxy)q uinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-oxopyrrolidin-1-yl)ethoxy)-q uinazoline; (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)-qui nazoline; and 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(3-(2-oxopyrrolidin-1-yl)propoxy)-q uinazoline; 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)quinazo line; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-3-yl)-methoxyqu inazoline; 4-(4-bromo-2-fluoroanilino)-7-3-(1,1-dixothiomorpholino)propoxy)-6-methoxyq uinazoline; 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)quinazol ine, 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]etho xy)-ethoxy)quinazoline; 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-([N-methyl-N-methoxyacetyl]amin o)-ethoxy)quinazoline; and 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-2-oxopyrrolidin-1-yl)ethoxy)quin azoline; 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)quinaz oline; (S)-4-4-chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-3-yl)-methox yquinazoline; and (R)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-3-yl)-metho xyquinazoline; 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)quinaz oline; and salts thereof. 12. A quinazoline derivative as claimed in any one of claims 1 and 7-11 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.1-3 alkylR.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.2-3 alkylR.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.50 but-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.51 but-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.2-3 alkylX.sup.2 C.sub.1-3 alkylX.sup.3 R.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.1-3 alkyl); 5) C.sub.2-3 alkylX.sup.5 R.sup.27 (wherein R.sup.27 is C.sub.1-2 alkyl and X.sup.5 is -S-, -SO-, -SO.sub.2 -, -SO.sub.2 NR.sup.30 -or- NR.sup.31 SO.sub.2 -(wherein R.sup.30 and R.sup.31 are as defined in claim 1)); and 6) C.sub.2-3 alkylX.sup.6 C.sub.2-3 alkylR.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: ##STR30## wherein: m is an integer from 1 to 2; R.sup.1 represents hydrogen, hydroxy, halogeno, nitro, trifuloromethyl, eyano, C.sub.1-3 alkyl, C.sub.1-3 alkoxy, C.sub.1-3 alkylthio, or -NR.sup.5 R.sup.6 (wherein R.sup.5 and R.sup.6, which may be the same or different, each represents hydrogen or C.sub.1-3 alkyl); R.sub.2 represents hydrogen, hydroxy, halageno, methoxy, amino or nitro; R.sub.3 represents hydroxy, halogeno, C.sub.1-3 alkyl, C.sub.1-3 alkoxy, C.sub.1-3 alkanoyloxy, 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.1-5 alkylR.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.1-5 alkyl through a carbon atom and which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C.sub.1-4 alkyl, C.sub.1-4 hydroxyalkyl and C.sub.1-4 alkoxy) or C.sub.1-5 alkylR.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.1-4 alkyl, C.sub.1-4 hydroxyalkyl and C.sub.1-4 alkoxy); 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 substituents selected from oxo, hydroxy, halogeno, C.sub.1-4 alkyl, C.sub.1-4 hydroyalkyl and C.sub.1-4 alkoxy); 3) C.sub.2-5 alkynylR.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.1-4 alkyl, C.sub.1-4 hydroxyalkyl and C.sub.1-4 alkoxy); 4) C.sub.1-5 alkylX.sup.2 C.sub.1-5 alkylX.sup.3 R.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.17 CO-, -CONR.sup.18-, -SO.sub.2 NR.sup.19 -, -NR.sup.20 SO- or -NR.sup.21 - (wherein R.sup.17, R.sup.18, R.sup.19, R.sup.20 and R.sup.21 each independetly represents hydrogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl) and R.sup.16 represents hydrogen or C.sub.1-3 alkyl); 5) C.sub.1-5 alkylX.sup.4 COR.sup.22 (wherein X.sup.4 represents -O- or -NR.sup.23 -(wherein R.sup.23 represents hydrogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl) and R.sup.22 represents -NR.sup.24 R.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.1-4 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl)); 6) C.sub.1-5 alkylX.sup.5 R.sup.27 (wherein X.sup.5 represents -O-, -S-, -SO.sub.2 -, -OCO-, -NR.sup.28 CO-, -CONR.sup.29 -, -SO.sub.2 NR.sup.30 -, -NR.sup.31 SO.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.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl) 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.1-4 alkyl, C.sub.1-4 hydroxyalkyl and C.sub.1-4 alkoxy; and 7) C.sub.1-3 alkoxyC.sub.2-4 alkyl or C.sub.1-4 alkyl; 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.1-3 alkanoyloxy; 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: ##STR31## 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: ##STR32## (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: ##STR33## (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 of compounds of formula I and salts thereof in which the group of formula IIa: ##STR34## (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: ##STR35## (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: ##STR36## (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: (wherein R.sup.14 is as defined im claim 1 and L.sup.1 is as defined herein); (d) the reaction of a compound of the formula VII: ##STR37## with a compound of the formula 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.1-5 alkylR.sup.53, wherein R.sup.53 is selected from one of the following three groups: 1) X.sup.7 R.sup.27 (wherein X.sup.7 represents --O--, --S--, --SO.sub.2 --, --NR.sup.54 CO--, --NR.sup.55 SO.sub.2 -- or --NR.sup.56 -- (wherein R.sup.54, R.sup.55 and R.sup.56 each independently represents hydrogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl) and R.sup.27 is as defined in claim 1); 2) X.sup.8 C.sub.1-5 alkylX.sup.3 R.sup.16 (wherein X.sup.8 represents --O--, --S--, --SO.sub.12 --, --NR.sup.57 CO--, --NR.sup.58 SO.sub.2 -- or --NR.sup.59 -- (wherein R.sup.57, R.sup.58 and R.sup.59 each independently represents hydrogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl) and X.sup.3 and R.sup.16 are as defined in claim 1); and 3) X.sup.9 C.sub.1-5 alkylR.sup.33 (wherein X.sup.9 represents --O--, --S--, --SO.sub.2 --, --NR.sup.60 CO--NR.sup.61 SO.sub.2 -- or --NR.sup.62 -- (wherein R.sup.60, R.sup.61 and R.sup.62 each independently represent hydrogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxyC.sub.2-3 alkyl) and R.sup.33 is as defined in claim 1); the reaction of a compound of the formula X: ##STR38## (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.1-5 alkyl) with a compound of the formula 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.2-5 alkylR.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.1-4 alkyl, C.sub.1-4 hydroxyalkyl, C.sub.1-4 alkoxy, carbamoyl, C.sub.1-4 alkylcarbamoyl, N,N-di(C.sub.1-4 alkyl)carbamoyl, C.sub.1-4 alkanoyl and C.sub.1-4 alkoxycarbonyl), the reaction of a compound of formula X (wherein R.sup.63 is C.sub.2-5 alkyl) with a compound of the formula 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.5 R.sup.6 where one or both of R.sup.5 and R.sup.6 are C.sub.1-3 alkyl, 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 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.