Imperial Chemical Industries Limited

National Research Development Corporation

Leslie R Hughes

John Oldfield

Howard Tucker

Stephen J Pegg

Andrew John Barker

Peter R Marsham

Alasdair T Glen

Neville S Crossley

Kenneth D Burrows

Peter Warner

The invention relates to quinazoline derivatives, or pharmaceutically-acceptable salts thereof, which possess anti-tumour activity; to processes for their manufacture; and to pharmaceutical compositions containing them. The invention provides a quinazoline of the formula: ##STR1## wherein R.sup.1 is hydrogen or amino, or alkyl or alkoxy each of up to 6 carbon atoms; or R.sup.1 is substituted alkyl or alkoxy each of up to 3 carbon atoms;

6-substituted quinazolines processing anti-tumor activity

Anti-tumor agents

A compound of the formula ##STR1## wherein X has the formula --CR.sup.5 .dbd.CR.sup.6 --, --C.ident.C-- or ##STR2## wherein ring A is phenyl, naphthyl or heterocyclic; wherein R.sup.1 is hydrogen, alkyl, alkanoyl or aroyl;

Alkene, alkyne or cycloalkylene derivatives

A quinazoline of the formula:- ##STR1## wherein R.sup.1 is alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkylthio, aryl, aryloxy, arylalkyl, halogeno, hydroxy, mercapto, pyridylthio, pyrimidinylthio, or substituted alkyl or alkoxy; wherein R.sup.2 is hydrogen, alkyl, alkenyl, alkynyl, substituted alkyl or alkanoyl; wherein Ar is phenylene, naphthylene or heterocyclene which is unsubstituted or bears one or more substituents and wherein R.sup.3 is such that R.sup.3 --NH.sub.2 is an amino acid; or a pharmaceutically-acceptable salt or ester thereof. The compounds possess anti-tumor activity.

Pharmaceutical compositions comprising quinazolin-4-one derivatives

The invention relates to a quinoline of the formula: ##STR1## wherein each of R.sup.1 and R.sup.2, which may be the same or different, is hydrogen, halogeno, hydroxy, cyano, carbamoyl, nitro or amino, alkyl, alkoxy, alkylthio, alkylamino, dialkylamino or alkanoylamino each of up to 4 carbon atoms, or substituted alkyl or alkoxy each of up to 3 carbon atoms, provided that both R.sup.1 and R.sup.2 are not hydrogen; the quinoline ring may bear further substituents; R.sup.3 is hydrogen or alkyl of up to 4 carbon atoms; R.sup.4 is hydrogen, alkyl, alkenyl or alkynyl each of up to 4 carbon atoms or substituted alkyl of up to 3 carbon atoms; Ar is phenylene, naphthylene or heterocyclene which is unsubstituted or which bears one or more substituents; R.sup.5 is such that R.sup.5 --NH.sub.2 is an amino acid; or a pharmaceutically-acceptable salt or ester thereof. The compounds possess anti-tumor activity.

Quinoline derivatives having anti-tumor activity

The invention relates to quinazoline derivatives, or pharmaceutically-acceptable salts thereof, which possess anti-tumor activity; to processes for their manufacture; and to pharmaceutical compositions containing them. The invention provides a quinazoline of the formula: ##STR1## wherein R.sup.1 is hydrogen or amino, or alkyl or alkoxy each of up to 6 carbon atoms; or R.sup.1 is substituted alkyl or alkoxy each of up to 3 carbon atoms;

Quinazoline derivatives possessing anti-tumor activity

A compound of the formula ##STR1## wherein X has the formula --CR.sup.5 .dbd.CR.sup.6 --, --C.tbd.C-- or ##STR2## wherein ring A is phenyl, naphthyl or heterocyclic; wherein R.sup.1 is hydrogen, alkyl, alkanoyl or aroyl;

A quinazoline of the formula: ##STR1## wherein R.sup.1 is alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkylthio, aryl, aryloxy, arylalkyl, halogeno, hydroxy, mercapto, pyridylthio, pyrimidinylthio, or substituted alkyl or alkoxy;

Method of producing antitumor effect using quinazolin-4-one derivatives

A compound of the formula ##STR1## wherein X has the formula ##STR2## wherein ring a is phenyl, naphthyl or heterocyclic; wherein R.sup.1 is hydrogen, alkyl, alkanoyl or aroyl; wherein R.sup.2, R.sup.3 and R.sup.4, which may be the same or different, each is an electron withdrawing substituent selected from halogeno, nitro, cyano, trifluoromethyl, alkylthio, alkylsulphinyl, and alkylsulphonyl or each is hydrogen, alkyl, alkoxy or dialkylamino provided that when ring A is phenyl or naphthyl at least one of R.sup.2, R.sup.3 and R.sup.4 is an electron-withdrawing substituent; wherein R.sup.5 and R.sup.6, which may be the same or different, each is hydrogen, halogeno or alkyl; wherein R.sup.7 is alkyl or halogenoalkyl; and wherein R.sup.8 is carbamoyl, alkyl, cycloalkyl, alkenyl, alkynyl, halogenoalkyl, halogenoalkenyl, halogenoalkynyl, alkanoyl, alkylcarbamoyl, dialkylcarbamoyl or aroyl; or wherein R.sup.8 is alkyl or alkenyl which bears one or more substituents selected from cyano, carbamoyl, amino, hydroxy, alkanoyl, alkoxy, alkylthio, alkenylthio, alkylsulphinyl, alkenylsulphinyl, alkylsulphonyl, alkenylsulphonyl, alkanoylamino, alkoxycarbonylamino, alkylsulphonamido, alkylamino, dialkylamino, dialkylsulphamoyl, aroyl, aryl, arylthio, arylsulphinyl, arylsulphonyl, heterocyclylthio, heterocyclylsulphinyl and heterocyclylsulphonyl; or wherein R.sup.8 has the formula ##STR3## wherein ring B is phenyl, naphthyl or heterocyclyl and wherein R.sup.2, R.sup.3 and R.sup.4 have any of the meanings stated above, provided that when R.sup.7 is methyl R.sup.8 is not also methyl.

Anti-tumour agents

The invention relates to quinazoline derivatives which possess anti-tumor activity; to processes for their manufacture; and to pharmaceutical compositions containing them. The invention provides a quinazoline of the formula: ##STR1## wherein R.sup.1 is hydrogen or amino, or alkyl or alkoxy each of up to 6 carbon atoms; or R.sup.1 is substituted alkyl or alkoxy each of up to 3 carbon atoms;

A quinazoline of the formula: ##STR1## wherein R.sup.1 is alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkylthio, aryl, aryloxy, arylthio, arylalkyl, halogeno, hydroxy or mercapto, or substituted alkyl or alkoxy;

A compound of the formula ##STR1## wherein X has the formula ##STR2## wherein ring A is phenyl, naphthyl or heterocyclic; wherein R.sup.1 is hydrogen, alkyl, alkanoyl or aroyl; wherein R.sup.2, R.sup.3 and R.sup.4, which may be the same or different, each is an electron withdrawing substituent selected from halogeno, nitro, cyano, trifluoromethyl, alkylthio, alkylsulphinyl and alkylsulphonyl or each is hydrogen, alkyl, alkoxy or dialkylamino provided that when ring A is phenyl or naphthyl at least one of R.sup.2, R.sup.3 and R.sup.4 is an electron-withdrawing substituent; wherein R.sup.5 and R.sup.6, which may be the same or different, each is hydrogen, halogeno or alkyl; wherein R.sup.7 is alkyl or halogenoalkyl; and wherein R.sup.8 is carbamoyl, alkyl, cycloalkyl, alkenyl, alkynyl, halogenoalkyl, halogenoalkenyl, halogenoalkynyl, alkanoyl, alkylcarbamoyl, dialkylcarbamoyl or aroyl; or wherein R.sup.8 is alkyl or alkenyl which bears one or more substituents selected from cyano, carbamoyl, amino, hydroxy, alkanoyl, alkoxy, alkylthio, alkenylthio, alkylsulphinyl, alkenylsulphinyl, alkylsulphonyl, alkenylsulphonyl, alkanoylamino, alkoxycarbonylamino, alkylsulphonamido, alkylamino, dialkylamino, dialkylsulphamoyl, aroyl, aryl, arylthio, arylsulphinyl, arylsulphonyl, heterocyclylthio, heterocyclylsulphinyl and heterocyclylsulphonyl; or wherein R.sup.8 has the formula ##STR3## wherein ring B is phenyl, naphthyl or heterocyclyl and wherein R.sup.2, R.sup.3 and R.sup.4 have any of the meanings stated above, provided that when R.sup.7 is methyl R.sup.8 is not also methyl.

Acylanilides of the formula ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are substituents defined in claim 1; wherein R.sup.4 is hydrogen or alkyl of up to 4 carbon atoms, or is joined to R.sup.5 as stated below;

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Macclesfield, United Kingdom

Leslie R Hughes