US5710158A Expired / Lapsed US ⏱️ 0.0 years remaining

Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase

Assignee: Aventis Pharmaceuticals Inc

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Filing: 1994-04-19

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Granted: 1998-01-20

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Expires: 2014-04-19

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Abstract

Abstract This invention relates to the modulation and/or inhibition of cell signaling, cell proliferation, cell inflammatory response, the control of abnormal cell growth and cell reproduction. More specifically, this invention relates to the use of mono- and/or bicyclic aryl or heteroaryl quinazoline compounds in inhibiting cell proliferation, including compounds which are useful protein tyrosine kinase (PTK) inhibitors. The method of treating cell proliferation using said quinazoline compounds and their use in pharmaceutical compositions is described.

Inventors

👤 Michael R. Myers
👤 Alfred P. Spada
👤 Martin P. Maguire
👤 Paul E. Persons

Bibliographic Details

Application Number —

Jurisdiction US

Data Source google_patents

Last Synchronized 2026-11-03 01:03

CPC Classifications

C; C07; C07D; C07D213/00; C07D213/02; C07D213/04; C07D213/24; C07D213/28; C07D213/30; A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/495; A61K31/505; A61K31/517; A61K31/535; A61K31/5375; A61K31/5377; A61P; A61P19/00; A61P35/00; A61P35/04; A61P37/00; A61P39/00; C07C; C07C43/00; C07C43/02; C07C43/20; C07C43/205; C07C43/2055; C07C43/225; C07C43/23; C07D213/60; C07D213/62; C07D213/63; C07D213/64; C07D215/00; C07D215/02; C07D215/12; C07D215/14; C07D215/16; C07D215/18; C07D215/20; C07D215/22; C07D215/233; C07D215/48; C07D215/50; C07D239/00; C07D239/70; C07D239/72; C07D239/74; C07D239/86; C07D239/88; C07D239/91; C07D239/93; C07D239/94; C07D241/00; C07D241/36; C07D241/38; C07D241/40; C07D241/42; C07D241/50; C07D241/52; C07D265/00; C07D265/04; C07D265/12; C07D265/14; C07D265/20; C07D265/22; C07D277/00; C07D277/60; C07D277/62; C07D277/64; C07D401/00; C07D401/02; C07D401/04; C07D403/00; C07D403/02; C07D403/04; C07D403/12; C07D405/00; C07D405/02; C07D405/04; C07D405/12; C07D409/00; C07D409/02; C07D409/04; C07D471/00; C07D471/02; C07D471/04

Claims Analysis

Total Claims: 20

Claim 1

Independent Claim 120 words

A method of inhibiting cell proliferation in a patient suffering from a disorder characterized by such proliferation comprising administering to a patient a compound of the formula: ##STR89## wherein Ar is selected from substituted or unsubstituted phenyl, α-naphthyl, β-naphthyl, indazolyl, indanyl, pyrazolyl, pyridinyl, indol-3-yl, benzodioxan-6-yl, 1,2,3,4-tetrahydroquinolin-1-yl, or 2,3-dihydroindol-1-yl where the substituents may be located at any appropriate position of the ring system and are described by R; X is a bond, O, S, NHCH 2 or NR 4 ; R independently includes hydrogen, alkyl, hydroxy, alkoxy, phenyl, aralkyl, alkylsulphonyl, haloalkyl or halo; R 5 is hydrogen or alkoxy; R 6 and R 7 are alkoxy; and R 4 is hydrogen, methyl, ethyl or benzyl; or a pharmaceutically acceptable salt thereof.

Claim 2

Independent Claim 120 words

Claim 3

Dependent Claim 38 words

The method according to claim 1 wherein the compound is selected from the group consisting of: 4-(3,4,5-trimethoxyphenylamino)-6,7-dimethoxyquinazoline, 4-(N-methyl-3,4,5-trimethoxyanilino)-6,7-dimethoxyquinazoline, 4-(N-methyl-4-methoxyanilino)-6,7-dimethoxyquinazoline, 4-(N-methyl-4-chloroanilino)-6,7-dimethoxyquinazoline, (6,7-dimethoxyquinazolin-4-yl)methyl-(3-trifluoromethylphenyl)amine, (3-chlorophenyl)-(6,7-dimethoxyquinazolin-4-yl)methylamine, N-phenyl-N-(6,7,8-dimethoxyquinazolin-4-yl)methylamine, benzyl-(6,7-dimethoxyquinazolin-4-yl)phenylamine, (3-chlorophenyl)-(6,7-dimethoxyquinazolin-4-yl)ethylamine, (6,7-dimethoxyquinazolin-4-yl) methyl-p-tolyl-amine, (4-methoxybenzyl)-(6,7-dimethoxyquinazolin-4-yl)amine, (3,5-dimethoxybenzyl)-(6,7-dimethoxyquinazolin-4-yl)amine, 4-(pyrazol-3-ylamino)-6,7-dimethoxyquinazoline, and 6,7-dimethoxy-4-(N-methylanilino)quinazoline; or a pharmaceutically acceptable salt thereof.

Claim 4

Dependent Claim 17 words

The method according to claim 1 wherein the compound is 4-(pyrazol-3-ylamino)-6,7-dimethoxyquinazoline or a pharmaceutically acceptable salt thereof.

Claim 5

Dependent Claim 29 words

The method according to claim 1 wherein the compound is selected from the group consisting of: (6,7-dimethoxyquinazolin-4-yl)-5-indazolylamine, 4- N-(5-indanyl)amino!-6,7-dimethoxyquinazoline, 4-(3,6-dioxananilino)-6,7-dimethoxyquinazoline, 6,7-dimethoxy-4-(α-naphthylamino)quinazoline, and 6,7-dimethoxy-4-(β-naphthylamino)quinazoline; or a pharmaceutically acceptable salt thereof.

Claim 6

Dependent Claim 27 words

The method according to claim 1 wherein the compound is selected from the group consisting of: 4-(3,4,5-trimethoxyphenoxyl)-6,7-dimethoxyquinazoline, 4-(3-methoxythiophenoxy)-6,7-dimethoxyquinazoline, 4-(3-chlorothiophenoxy)-6,7-dimethoxyquinazoline, and 4-(3-chlorophenoxy)-6,7-dimethoxyquinazoline; or a pharmaceutically acceptable salt thereof.

Claim 7

Dependent Claim 38 words

The method according to claim 1 wherein the compound is selected from the group consisting of: 4-(4-hydroxyphenyl)-6,7-dimethoxyquinazoline, 4-(naphthalen-1-yl)-6,7-dimethoxyquinazoline, 4-(naphthalen-2-yl)-6,7-dimethoxyquinazoline, 4-(3-fluoro-4-methoxyphenyl)-6,7-dimethoxyquinazoline, 4-(3-phenylphenyl)-6,7-dimethoxyquinazoline, 4-(2-methoxypyridin-5-yl)-6,7-dimethoxyquinazoline, 4-(1 -benzylindol-3-yl)-6,7-dimethoxyquinazoline, 4-(indol-3-yl)-6,7-dimethoxyquinazoline, 4-(1 -methylindol-3-yl)-6,7-dimethoxyquinazoline, 4-(1-methylsulphonylindol-3-yl)-6,7-dimethoxyquinazoline, (±)-4-(2-methyl-1,2,3,4-tetrahydroquinolin-1-yl)-6,7-dimethoxyquinazoline, 4-(1,2,3,4-tetrahydroquinolin-1-yl)-6,7-dimethoxyquinazoline, and 4-(2,3-dihydroindol-1-yl)-6,7-dimethoxyquinazoline; or a pharmaceutically acceptable salt thereof.

Claim 8

Dependent Claim 27 words

A compound selected from the group consisting of: 4-(3,4,5-trimethoxyphenylamino)-6,7-dimethoxyquinazoline, 4-(N-methyl-3,4,5-trimethoxyanilino)-6,7-dimethoxyquinazoline, 4-(N-methyl-4-methoxyanilino)-6,7-dimethoxyquinazoline, 4-(N-methyl-4-chloroanilino)-6,7-dimethoxyquinazoline, (6,7-dimethoxyquinazolin-4-yl)methyl-(3-trifluoromethylphenyl)amine, (3-chlorophenyl)-(6,7-dimethoxyquinazolin-4-yl)methylamine, N-phenyl-N-(6,7,8-dimethoxyquinazolin-4-yl)methylamine, (3-chlorophenyl)-(6,7-dimethoxyquinazolin-4-yl)ethylamine, (6,7-dimethoxyquinazolin-4-yl)methyl-p-tolyl-amine, (4-methoxybenzyl)-(6,7-dimethoxyquinazolin-4-yl)amine, (3,5-dimethoxybenzyl)-(6,7-dimethoxyquinazolin-4-yl)amine, and 6,7-dimethoxy-4-(N-methylanilino)quinazoline; or a pharmaceutically acceptable salt thereof.

Claim 9

Dependent Claim 27 words

Claim 10

Dependent Claim 11 words

A compound which is 4-(pyrazol-3-ylamino)-6,7-dimethoxyquinazoline or a pharmaceutically acceptable salt thereof.

Claim 11

Dependent Claim 11 words

A compound which is 4-(pyrazol-3-ylamino)-6,7-dimethoxyquinazoline or a pharmaceutically acceptable salt thereof.

Claim 12

Dependent Claim 21 words

A compound selected from the group consisting of: (6,7-dimethoxyquinazolin-4-yl)-5-indazolylamine, 4- N-(5-indanyl)amino!-6,7-dimethoxyquinazoline, 4-(3,6-dioxananilino)-6,7-dimethoxyquinazoline, 6,7-dimethoxy-4-(α-naphthylamino)quinazoline, and 6,7-dimethoxy-4-(β-naphthylamino)quinazoline; or a pharmaceutically acceptable salt thereof.

Claim 13

Dependent Claim 21 words

Claim 14

Dependent Claim 19 words

A compound selected from the group consisting of: 4-(3,4,5-trimethoxyphenoxy)-6,7-dimethoxyquinazoline, 4-(3-methoxythiophenoxy)-6,7-dimethoxyquinazoline, 4-(3-chlorothiophenoxy)-6,7-dimethoxyquinazoline, and 4-(3-chlorophenoxy)-6,7-dimethoxyquinazoline; or a pharmaceutically acceptable salt thereof.

Claim 15

Dependent Claim 19 words

Claim 16

Dependent Claim 28 words

A compound selected from the group consisting of: 4-(4-hydroxyphenyl)-6,7-dimethoxyquinazoline, 4-(naphthalen-1-yl)-6,7-dimethoxyquinazoline, 4-(naphthalen-2-yl)-6,7-dimethoxyquinazoline, 4-(3-fluoro-4-methoxyphenyl)-6,7-dimethoxyquinazoline, 4-(3-phenylphenyl)-6,7-dimethoxyquinazoline, 4-(2-methoxypyridin-5-yl)-6,7-dimethoxyquinazoline, 4-(1-benzylindol-3-yl)-6,7-dimethoxyquinazoline, 4-(indol-3-yl)-6,7-dimethoxyquinazoline, 4-(1-methylindol-3-yl)-6,7-dimethoxyquinazoline, 4-(1-methylsulphonylindol-3-yl)-6,7-dimethoxyquinazoline, (±)-4-(2-methyl-1,2,3,4-tetrahydroquinolin-1-yl)-6,7-dimethoxyquinazoline, 4-(1,2,3,4-tetrahydroquinolin-1-yl)-6,7-dimethoxyquinazoline, and 4-(2,3-dihydroindol-1-yl)-6,7-dimethoxyquinazoline; or a pharmaceutically acceptable salt thereof.

Claim 17

Dependent Claim 28 words

Claim 18

Dependent Claim 15 words

A compound according to claim 9 which is 6,7-dimethoxy-4-(α-naphthylamino)quinazoline or a pharmaceutically acceptable salt thereof.

Claim 19

Dependent Claim 15 words

A compound according to claim 11 which is 6,7-dimethoxy-4-(1-methylsulphonylindol-3-yl)quinazoline or a pharmaceutically acceptable salt thereof.

Claim 20

Dependent Claim 15 words

A compound according to claim 11 which is 4-(1-benzylindol-3-yl)-6,7-dimethoxyquinazoline or a pharmaceutically acceptable salt thereof.

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USPTO Annuity & Maintenance Windows

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	2001-01-19	2001-07-21	2002-01-20	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2005-01-19	2005-07-21	2006-01-20	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2009-01-19	2009-07-21	2010-01-20	$7700.00	Window Closed / Lapsed

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