Patent EP0031237A1 successfully refreshed from Google Patents.
EP0031237A1
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EP
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Quinazoline derivatives, processes for their preparation, compositions containing them and their use as anti-cancer agents
Assignee: BTG International Ltd
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Filing: 1980-12-16
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Granted: —
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Expires: 2000-12-16
Abstract
Abstract Quinazoline derivatives of formula: wherein r represents: 1) a straight or branched chain unsaturated hydrocarbon group, or 2) a straight or branched chain saturated or unsaturated hydrocarbon group which is substituted by at least one: heteroatom, the or each heteroatom being halogeno when R is a C 1 hydrocarbon group; or saturated carbocyclic group; or group containing at least one heteroatom, the or each heteroatom being 0, N or S when R contains a cyclic group; and n is 0 or an integer of 1-4; X or, when n is an integer of at least 2, each X independently, represents a halogeno, C 1 -C 4 alkyl, aryl or aralkyl group or a group including at least one heteroatom; and Y represents a group of formula:- wherein m . 1 (poly-L-glutamates); and the pharmaceutically acceptable salts and esters thereof, which are suitable as anti-cancer agents.
Inventors
- 👤 Terence Richard Jones
- 👤 Kenneth Reginald Harrap
- 👤 Alan Hilary Calvert
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-02 16:29
CPC Classifications
C; C07; C07D; C07D239/00; C07D239/70; C07D239/72; C07D239/95; C07D205/00; C07D205/02; C07D205/04
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
140 words
A compound of formula: wherein R represents: 1) a straight or branched chain unsaturated hydrocarbon group, or 2) a straight or branched chain saturated or unsaturated hydrocarbon group which is substituted by at least one: heteroatom, the or each heteroatom being halogeno when R is a C 1 hydrocarbon group; or saturated carbocyclic group; or group containing at least one heteroatom, the or each heteroatom being O, N or S when R contains a cyclic group; n is O or an integer of 1 - 4; X or, when n is an integer of at least 2, each X independently, represents a halogeno, C 1 -C 4 alkyl, aryl or aralkyl group or a group including at least one heteroatom; and Y represents a group of formula:- wherein m ≥ 1 (poly-L-glutamates); or a pharmaceutically acceptable salt or ester thereof.
Claim 2
Dependent Claim
140 words
A compound of formula: wherein R represents: 1) a straight or branched chain unsaturated hydrocarbon group, or 2) a straight or branched chain saturated or unsaturated hydrocarbon group which is substituted by at least one: heteroatom, the or each heteroatom being halogeno when R is a C 1 hydrocarbon group; or saturated carbocyclic group; or group containing at least one heteroatom, the or each heteroatom being O, N or S when R contains a cyclic group; n is O or an integer of 1 - 4; X or, when n is an integer of at least 2, each X independently, represents a halogeno, C 1 -C 4 alkyl, aryl or aralkyl group or a group including at least one heteroatom; and Y represents a group of formula:- wherein m ≥ 1 (poly-L-glutamates); or a pharmaceutically acceptable salt or ester thereof.
Claim 3
Dependent Claim
18 words
A compound according to claim 1 wherein R contains up to 6 carbon atoms in its hydrocarbon chain.
Claim 4
Dependent Claim
17 words
A compound according to claim 2 wherein R contains a total of up to 4 carbon atoms.
Claim 5
Dependent Claim
34 words
A compound according to claim 2 or 3, wherein R is an unsaturated hydrocarbon group, optionally substituted as defined under 2) in claim 1, having 3 or 4 carbon atoms in the hydrocarbon chain.
Claim 6
Dependent Claim
12 words
A compound according to claim 4 wherein R is allyl or propargyl.
Claim 7
Dependent Claim
33 words
A compound according to claim 2 or 3, wherein R is a saturated hydrocarbon group substituted as defined under 2) in claim 1, having 1 to 3 carbon atoms in the hydrocarbon chain.
Claim 8
Dependent Claim
27 words
A compound according to any one of claims 1 to 4 and 6 wherein the group R contains 1-4 heteroatoms selected from halogeno, O, N and S.
Claim 9
Dependent Claim
37 words
A compound according to claim 7 wherein the substituent of R is: -CN, - COOH or a salt or ester thereof, -OH, =O,halogeno, NH 2 , -CONH 2 , -CO-C 6 H 5 , oxiranyl or 5-uracilyl.
Claim 10
Dependent Claim
26 words
A compound according to claim 8 wherein R is: cyanoalkyl, carboxyalkyl, alkoxycarbonylalkyl,hydroxyalkyl, haloalkyl, carbamoylalkyl, benzoylalkyl or oxiranylalkyl, the alkyl groups containing 1 to 6 carbon atoms.
Claim 11
Dependent Claim
21 words
A compound according to claim 8, wherein R is: cyanomethyl, carboxymethyl, ethoxycarbonylmethyl, 3-hydroxypropyl, 2-chloro-, 2-bromo-or 2-fluoro-ethyl, carbamoylmethyl, phenacyl, oxiranylmethyl or 5-uracilylmethyl.
Claim 12
Dependent Claim
26 words
A compound according to any one of the preceding claims, wherein n is 1 or 2 and X is halogeno or C 1 -C 4 alkyl.
Claim 13
Dependent Claim
16 words
A compound according to claim 11 wherein n is 1 and X is chloro or methyl.
Claim 14
Dependent Claim
31 words
A compound according to any one of the preceding claims, wherein Y is an L-glutamic acid residue, one or both of the acid groups optionally being in salt or ester form.
Claim 15
Dependent Claim
21 words
N-(4-(N-((2-amino-4-hydroxy-6-quinazolinyl) methyl)prop-2-ynylamino)benzoyl)-L-glutamic acid, N-(2-methyl-4-(N - ((2-amino-4-hydroxy-6-quinazolinyl) methyl)prop-2-ynylamino)benzoyl)-L-glutamic acid or N -(2-chloro-4-(N-((2-amino-4-hydroxy-6-quinazolinyl) methyl)prop-2-ynylamino)benzoyl)-L-glutamic acid or a salt or ester of these compounds.
Claim 16
Dependent Claim
21 words
N-(4-(N-((2-amino-4-hydroxy-6-quinazolinyl) methyl)prop-2-ynylamino)benzoyl)-L-glutamic acid, N-(2-methyl-4-(N - ((2-amino-4-hydroxy-6-quinazolinyl) methyl)prop-2-ynylamino)benzoyl)-L-glutamic acid or N -(2-chloro-4-(N-((2-amino-4-hydroxy-6-quinazolinyl) methyl)prop-2-ynylamino)benzoyl)-L-glutamic acid or a salt or ester of these compounds.
Claim 17
Dependent Claim
20 words
A compound according to any one of the preceding claims in the form of a disodium salt or diethyl ester.
Claim 18
Dependent Claim
145 words
-16. A process for preparing a compound as claimed in claim 1 which comprises completely or partially deprotecting a compound of formula: wherein X and n are as defined in claim 1, R 2 is equivalent to R as defined in claim I or is a group R in protected form, R 1 is hydrogen or an amino-protecting group and Y' represents a group of formula a), b) or c) as defined in claim I for Y or a salt of said groups or said groups in partially or completely protected form, the protecting group in Y' being an ester group or other protecting group, with the proviso that the compound of formula Ia contains at least one protecting group and that, if deprotection is carried out to remove more than one protecting group, the deprotections may be carried out simultaneously or in any order.
Claim 19
Dependent Claim
79 words
A process for preparing a compound as claimed in claim 1 which comprises coupling a compound of formula: wherein R 1 is as defined in claim 16 and X" is a leaving group, with a compound of formula: wherein R 2 , X, n and Y' are as defined in claim 16,to form a compound of formula (Ia) as defined in claim 16 but which need contain no protecting groups, and if necessary, deprotecting the compound of formula Ia.
Claim 20
Dependent Claim
64 words
A process according to claim 17 wherein the compound of formula II,wherein Y' is in protected form,is prepared by reacting a compound of formula wherein X, n and Y' are as defined in claim 17 with Y' being in protected form, with a compound of formula R 2 X' wherein R 2 is as defined in claim 17 and X' is a leaving group.
Claim 21
Dependent Claim
78 words
A process according to claim 16 wherein the compound of formula Ia,wherein R 1 is an amino-protecting group and Y' is in protected form,is prepared by reacting a compound of formula: wherein X , n and Y' are as defined in claim 16, Y' ' being in protected form, and R 1 is an amino-protecting group,with a compound of formula R 2 X' wherein R 2 is as defined in claim 16 and X' is a leaving group.
Claim 22
Dependent Claim
58 words
A process according to claim 19 wherein the compound of formula Ib is prepared by reacting a compound of formula: wherein R 1 is an amino-protecting group and Z is -CH 2 -X" wherein X" is a leaving group, CN or CHO, with a compound of formula: wherein X, Y' and n are as defined in claim 19.
Claim 23
Dependent Claim
37 words
A process according to any one of claims 16 to 20 wherein the compound of formula I produced is an acid which is subsequently converted to a pharmaceutically acceptable salt by addition of an acid or base.
Claim 24
Dependent Claim
28 words
A pharmaceutical composition comprising, as active ingredient, a compound as claimed in any one of claims 1 to 15 in association with a pharmaceutically acceptable carrier or diluent.
Claim 25
Dependent Claim
10 words
A composition according to claim 22 in sterile injectable form.
Claim 26
Dependent Claim
18 words
A compound as claimed in any one of claims 1 to 15 for use as an anti-cancer agent.
References Cited (Backward Citations)
US3472851A
Cited
US3471498A
Cited
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