Claims
- 1. A method for the selective treatment of cell growth and differentiation characterized by activity of the human epidermal growth factor receptor type 2 (HER2) comprising administering to a patient in need of such treatment an HER2 receptor inhibiting effective amount of a compound of the formula: ##STR12## wherein A is a substituted or unsubstituted monocyclic aryl or heteroaryl ring selected from phenyl, pyrrolyl, thienyl, furyl, thiazolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, isothiazolyl, isoxazolyl and oxazolyl;
- X is a bond, O, S, SO, SO.sub.2, OCH.sub.2, CR.sub.4 .dbd.CR.sub.4, C.tbd.C, NR.sub.4 or NR.sub.4 CH.sub.2 ;
- R independently includes hydrogen, alkyl, phenyl, halophenyl, aralkyl, hydroxy, alkoxy, aryloxy, acyloxy, halo, haloalkyl, amino, mono- and di-alkylamino, acylamino, carboxy, amido, mono- and di-alkylamido, alkylthio, alkylsulfinyl, and alkylsulfonyl;
- R.sub.4 is hydrogen, alkyl or aralkyl; and
- R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are independently hydrogen, alkoxy or aralkoxy; or
- a pharmaceutically acceptable salt thereof.
- 2. A method for the selective treatment of cell growth and differentiation characterized by activity of the human epidermal growth factor receptor type 2 (HER2) comprising administering to a patient in need of such treatment an HER2 receptor inhibiting effective amount of a compound of the formula: ##STR13## wherein A is a substituted or unsubstituted bicyclic aryl or heteroaryl ring selected from naphthyl, tetralinyl, 1,2,3,4-tetrahydroquinolinyl, benzofuryl, benzothienyl, indanyl, indolyl, indolinyl, 1,3-benzodioxolyl, benzodioxanyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, quinazolinyl and quinoxalinyl.
- X is a bond, O, S, SO, SO.sub.2, OCH.sub.2, CR.sub.4 .dbd.CR.sub.4, C.tbd.C, NR.sub.4 or NR.sub.4 CH.sub.2 ;
- R independently includes hydrogen, alkyl, phenyl, halophenyl, aralkyl, hydroxy, alkoxy, aryloxy, acyloxy, halo, haloalkyl, amino, mono- and di-alkylamino, acylamino, carboxy, amido, mono- and di-alkylamido, alkylthio, alkylsulfinyl, and alkylsulfonyl;
- R.sub.4 is hydrogen, alkyl or aralkyl; and
- R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are independently hydrogen, alkoxy or aralkoxy; or a pharmaceutically acceptable salt thereof.
- 3. A method for the selective treatment of cell growth and differentiation characterized by activity of the human epidermal growth factor receptor type 2 (HER2) comprising administering to a patient in need of such treatment an HER2 receptor inhibiting effective amount of a compound of the formula: ##STR14## wherein A is a substituted or unsubstituted monocyclic cycloalkyl or heterocycloalkyl ring selected from cyclopentyl, cyclohexyl, cycloheptyl, decalinyl, piperdinyl, piperazinyl, morpholinyl or decahydroquinolinyl.
- X is a bond, O, S, SO, SO.sub.2, OCH.sub.2, CR.sub.4 .dbd.CR.sub.4, C.tbd.C, NR.sub.4 or NR.sub.4 CH.sub.2 ;
- R independently includes hydrogen, alkyl, phenyl, halophenyl, aralkyl, hydroxy, alkoxy, aryloxy, acyloxy, halo, haloalkyl, amino, mono- and di-alkylamino, acylamino, carboxy, amido, mono- and di-alkylamido, alkylthio, alkylsulfinyl, and alkylsulfonyl;
- R.sub.4 is hydrogen, alkyl or aralkyl; and
- R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are independently hydrogen, alkoxy or aralkoxy; or a pharmaceutically acceptable salt thereof.
- 4. A method for the selective treatment of cell growth and differentiation characterized by activity of the human epidermal growth factor receptor type 2 (HER2) comprising administering to a patient in need of such treatment an HER2 receptor inhibiting effective amount of a compound of the formula: ##STR15## wherein A is a substituted or unsubstituted bicyclic cycloalkyl or heterocycloalkyl ring selected from decalinyl or decahydroquinolinyl.
- X is a bond, O, S, SO, SO.sub.2, OCH.sub.2, CR.sub.4 .dbd.CR.sub.4, C.tbd.C, NR.sub.4 or NR.sub.4 CH.sub.2 ;
- R independently includes hydrogen, alkyl, phenyl, halophenyl, aralkyl, hydroxy, alkoxy, aryloxy, acyloxy, halo, haloalkyl, amino, mono- and di-alkylamino, acylamino, carboxy, amido, mono- and di-alkylamido, alkylthio, alkylsulfinyl, and alkylsulfonyl;
- R.sub.4 is hydrogen, alkyl or aralkyl; and
- R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are independently hydrogen, alkoxy or aralkoxy; or a pharmaceutically acceptable salt thereof.
- 5. A method for the selective treatment of cell growth and differentiation characterized by activity of the human epidermal growth factor receptor type 2 (HER2) comprising administering to a patient in need of such treatment an HER2 receptor inhibiting effective amount of a compound of the formula: ##STR16## wherein A is substituted and unsubstituted phenyl, pyridyl, thienyl, furyl, pyrazolyl, naphthyl, tetralinyl, 1,2,3,4-tetrahydroquinolinyl, indanyl, indolyl, indolinyl, quinolinyl, tetrahydroquinolinyl, cyclohexyl, piperdinyl or piperazinyl;
- X is a bond, O, S, or NR.sub.4 ;
- R is hydrogen, alkyl, alkoxy, halo, haloalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenyl and aralkyl;
- R.sub.4 is hydrogen, alkyl or aralkyl; and
- R.sub.5, R.sub.6, R.sub.7, and R.sub.8 are independently hydrogen or alkoxy; or a pharmaceutically acceptable salt thereof.
- 6. A method for the selective treatment of cell growth and differentiation characterized by activity of the human epidermal growth factor receptor type 2 (HER2) comprising administering to a patient in need of such treatment an HER2 receptor inhibiting effective amount of a compound of the formula: ##STR17## wherein A is substituted and unsubstituted phenyl, naphthyl or indolyl;
- X is a bond;
- R is hydrogen, methoxy, ethoxy, chloro, trifluoromethyl, methylsulfonyl, phenyl and benzyl;
- R.sub.4 is hydrogen, methyl or benzyl; and
- R.sub.5, R.sub.6, R.sub.7, and R.sub.8 are independently hydrogen or methoxy; or a pharmaceutically acceptable salt thereof.
- 7. A method according to claim 1 where the compound administered is 4-(2-phenylethylenyl)-6,7-dimethoxyquinazoline or a pharmaceutically acceptable thereof.
- 8. A method according to claim 2 where said compound administered is 6,7-dimethoxy-4-naphthalen-1yl-ethynylquinazoline or a pharmaceutically acceptable thereof.
- 9. A method according to claim 5 where said compound administered is selected from:
- 4-(2-methoxypyridin-5-yl)-6,7-dimethoxyquinazoline,
- 4-(4-phenylpiperidin-1-yl)-6,7-dimethoxyquinazoline,
- 4-�4-(3-chlorophenyl)piperazin-1-yl!-6,7-dimethoxyquinazoline and
- 4-(1,2,3,4-tetrahydroquinolin-1 -yl)-6,7-dimethoxyquinazoline or a pharmaceutically acceptable thereof.
- 10. A method according to claim 5 where said compound administered is selected from:
- 6,7-dimethoxy-4-(.beta.-naphthylamino)quinazoline,
- 4-�N-(5-indanyl)amino!-6,7-dimethoxyquinazoline,
- N-benzyl-N-(6,7-dimethoxyquinazolin-4-yl)-N-phenylamine,
- 6,7-dimethoxy-4-(N-methylanilino) quinazoline,
- N-(3-chlorophenyl)-N-(6,7-dimethoxyquinazolin-4-yl)-N-methylamine,
- 4-(3-aminopyrazolyl)-6,7-dimethoxyquinazoline and
- 4-(cyclohexylanilino)-6,7-dimethoxyquinazoline or a pharmaceutically acceptable thereof.
- 11. A method according to claim 5 where the compound administered is 6,7-dimethoxy-4-(.alpha.-naphthylamino)quinazoline or a pharmaceutically acceptable salt thereof.
- 12. A method according to claim 6 where said compound administered is selected from:
- 4-(naphthalen-1-yl)-6,7-dimethoxyquinazoline,
- 4-(naphthalen-2-yl)-6,7-dimethoxyquinazoline,
- 4-(3-phenylphenyl)-6,7-dimethoxyquinazoline,
- 4-(indol-3-yl)-6,7-dimethoxyquinazoline and
- 4-(1-methylindol-3-yl)-6,7-dimethoxyquinazoline or a pharmaceutically acceptable salt thereof.
- 13. A method according to claim 6 where the compound administered is 4-(1-benzylindol-3-yl)-6,7-dimethoxyquinazoline or a pharmaceutically acceptable salt thereof.
Parent Case Info
This application is a continuation-in-part application of PCT International Application Serial No. PCT/US94/14180 having International filing date of Dec. 8, 1994, and a CIP application of United States and U.S. Ser. No. 08/166,199, filed Dec. 10, 1993 , now U.S. Pat. No. 5,480,893, which is a continuation-in-part application of U.S. Ser. No. 07/988,515, filed Dec. 10, 1992, now abandoned, which is a continuation-in-part application of U.S. Ser. No. 07/698,420, filed May 10, 1991, now abandoned, and PCT International Application Serial No. PCT/US92/03736 filed May 6, 1992.
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Continuation in Parts (3)
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Parent |
166199 |
Dec 1993 |
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Parent |
988515 |
Dec 1992 |
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Parent |
698420 |
May 1991 |
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