Claims
- 1. A quinoline derivatives according to the formula 1
- 2. The quinoline derivative of claim 1, wherein in R, R1, R2, and R3, said C1-8 alkylcarbonyl is acetyl, said C1-8 alkoxy is benzyloxy or phenylethoxy, said fluorine atoms are trifluoromethyl, said C2-6 alkenyl is allyl, said C2-6 alkynyl is ethynyl or propargyl, said cyano-C1-6 alkyl is cyanomethyl, said C1-8 alkoxy-carbonyl is tert-butoxycarbonyl, and said C1-8 alkoxy is methoxy or ethoxy, and in R4 said fluorine atoms are trifluoromethyl, said C1-8 alkoxy is methoxy or ethoxy, and said C1-2 alkylene group is a methylene group.
- 3. The quinoline derivative of formula 1 of claim 1, wherein R, R1, R2, R3, X, Z, P, Q, n and m have the meanings given in claim 1.
R4 is a straight-chain or branched C1-20 alkyl radical which can be saturated or unsaturated, with one to three double and/or triple bonds, and which can be unsubstituted or optionally substituted on the same or different Catoms by one, two or more aryl, heteroaryl, halogen, C1-6 alkoxy, amino, mono-C1-4 alkylamino or di-C4 alkylamino; a phenyl ring or a naphthyl ring, each of which can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of straight-chain or branched C1-8 alkyl, C3-7 cycloalkyl, halogen, cyano, C1-6 alkoxycarbonylamino, C1-6 alkoxy, carboxyl, C1-6 alkoxycarbonyl, straight-chain or branched C1-6 alkyl which is substituted by one or more fluorine atoms, hydroxyl, straightchain or branched C1-6 alkoxy, benzyloxy, nitro, amino, mono-C1-4 alkylamino, di-C1-4 alkylamino, aryl, which can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of straight-chain or branched C1-8 alkyl, C3-7 cycloalkyl, carboxyl, straight-chain or branched C1-6 alkoxycarbonyl, by trifluoromethyl, hydroxyl, straight-chain or branched C1-8 alkoxy, benzyloxy, nitro, amino, mono-C1-4 alkylamino, di-C1-4 alkylamino, cyano, straight-chain or branched cyano-C1-6 alkyl; a 2-, 4-, 5- or 6-pyrimidinyl radical, or a 2-, 4-, 5- or 6-pyrimidinyl-C1-4 alkyl wherein the C1-4 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O) and the 2-, 4-, 5- or 6-pyrimidinyl radical can be unsubstituted or mono- or up to trisubstituted by the same or different substituents from the group of hydrogen, or Y wherein Y is a C1-6 alkyl, halogen, nitro, amino, mono-C1-6 alkylamino, di-C1-6 alkylamino, hydroxyl, C-6 alkoxy, benzyloxy, carboxyl, C1-6 alkoxycarbonyl, C1-6 alkoxycarbonylamino or C1-6 alkyl which is mono- or polysubstituted by fluorine, C6-10 aryl and C6-10 aryl-C1-6 alkyl; a 3-, 4-, 5- or 6-pyridazinyl radical, or a 3-, 4-, 5- or 6-pyridazinyl-C1-4 alkyl r wherein the C1-4 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 3-, 4-, 5- or 6-pyridazinyl radical can be unsubstituted or mono- or up to trisubstituted by the same or different substituents from the group of hydrogen, or Y; a 2-, 3-, 5- or 6-pyrazinyl radical, or a 2-, 3-, 5- or 6-pyrazinyl-C1-4 alkyl radical, wherein the C1-4 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 2-, 3-, 5- or 6-pyrazinyl radical can be unsubstituted or mono- or up to trisubstituted by the same or different substituents from the group of hydrogen, or Y; a 3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl radical, or a 3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl-C1-4 alkyl radical, wherein the C1-4 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-4 alkyl, halogen or oxo (═O), and the 3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl radical can be unsubstituted or mono- or up to pentasubstituted by the same or different substituents from the group of hydrogen, or Y; a 2-, 4-, 5-, 6-, 7-, or 8-quinazolinyl radical, or a 2-, 4-, 5-, 6-, 7 or 8-quinazolinyl-C1-4 alkyl radical, wherein the C1-4 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of hydrogen, C1-6 alkyl, halogen or oxo (═O), and the 2-, 4-, 5-, 6-, 7-, or 8-quinazolinyl radical can be unsubstituted or mono- or up to pentasubstituted by the-same or different substituents from the group of hydrogen, or Y; a 2-, 3-, 5-, 6-, 7-, or 8-quinoxalinyl radical, or a 2-, 3-, 5-, 6-, 7-, or 8-quinoxalinyl-C1-4 alkyl radical, wherein the C1-4 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 2-, 3-, 5-, 6-, 7-, or 8-quinoxalinyl radical can be unsubstituted or mono- or up to pentasubstituted by the same or different substituents from the group of hydrogen, or Y; a 1-, 4-, 5-, 6-, 7-, or 8-phthalazinyl radical, or a 1-, 4-, 5-, 6-, 7-, or 8-phthalazinyl-C1-4 alkyl radical, wherein the C1-4 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 1-, 4-, 5-, 6-, 7-, or 8-phthalazinyl radical can be unsubstituted or mono- or up to pentasubstituted by the same or different substituents from the group of hydrogen, or Y; a 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl radical, or a 2-, 3-, 4-, 5-, 6-, 7 or 8-quinolyl-C1-4 alkyl radical, wherein the C1-4 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl radical can be unsubstituted or mono- or up to hexasubstituted by the same or different substituents from the group of hydrogen, or Y; a 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl radical, or a 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl-C1-4 alkyl radical, wherein the C1-4 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 1-, 4-, 5-, 6-, 7- or 8-isoquinolyl radical can be unsubstituted or mono- or up to hexasubstituted by the same or different substituents from the group of hydrogen, or Y; a 2-, 6-, 8- or 9-[9H]-purinyl radical, or a 2-, 6-, 8- or 9-[9H]-purinyl-C1-4 alkyl radical, wherein the C1-4 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 2-, 6-, 8- or 9[9H]-purinyl radical can be unsubstituted or mono- to trisubstituted by the same or different substituents from the group of hydrogen, or Y; a 2-, 6-, 7- or 8-[7H]-purinyl radical, or a 2-, 6-, 7- or 8-[7H]-purinyl-C1-4 alkyl radical, wherein the C1-4 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 2-, 6-, 7- or 8-[7H]-radical can be unsubstituted or mono- or up to trisubstituted by the same or different substituents from the group of hydrogen, or Y; a 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl radical, or a 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl-C1-4 alkyl radical, where the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl radical can be unsubstituted or mono- to octasubstituted by the same or different substituents from the group of hydrogen, or Y; a 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-phenanthridinyl radical, or a 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-phenanthridinyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono-or polysubstituted by the same or different substituents from the group of hydrogen, C1-6 alkyl, halogen or oxo (═O), and the 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-phenanthridinyl radical can be unsubstituted or mono- or up to octasubstituted by the same or different substituents of Y; a 2-, 3-, 4-, 5- or 6-pyridyl radical where the 2-, 3-, 4-, 5- or 6-pyridyl radical can be unsubstituted or mono- or up to tetrasubstituted by the same or different substituents from the group of hydrogen, or Y; a 2-, 3-, 4-, 5- or 6-pyridinyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 2-, 3-, 4-, 5- or 6-pyridinyl radical can be unsubstituted or mono- or up to tetrasubstituted by the same or different substituents from the group of hydrogen, or Y; a 2-, 3-, 4- or 5-thienyl radical, or a 2-, 3-, 4- or 5-thienyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 2-, 3-, 4- or 5-thienyl radical can be unsubstituted or mono- or up to trisubstituted by the same or different substituents from the group of hydrogen, or Y; a 2-, 4-, or 5-thiazolyl radical, or a 2-, 4-, or 5-thiazolyl c1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 2-, 4-, or 5-thiazolyl radical can be unsubstituted or mono- or disubstituted by the same or different substituents from the group of hydrogen, or Y; a 3-, 4-, or 5-isothiazolyl radical, or a 3-, 4-, or 5-isothiazolyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 3-, 4-, or 5-isothiazolyl radical can be unsubstituted or mono- or disubstituted by the same or different substituents from the group of hydrogen, or Y; a 2-, 4-, 5-, 6-, or 7-benzothiazolyl radical, or a 2-, 4-, 5-, 6-, or 7-benzothiazolyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 2-, 4-, 5-, 6-, or 7-benzothiazolyl radical can be unsubstituted or mono- or up to tetrasubstituted by the same or different substituents from the group of hydrogen, or Y; a 1-, 2-, 4-, or 5-imidazolyl radical, or a 1-, 2-, 4-, or 5 imidazolyl-C1-6 alkyl r wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 1-, 2-, 4-, or 5-imidazolyl radical can be unsubstituted or mono- or up to trisubstituted by the same or different substituents from the group of hydrogen, or Y; a 1-, 3-, 4-, or 5-pyrazolyl radical, or a 1-, 3-, 4- or 5-pyrazolyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 1-, 3-, 4- or 5-pyrazolyl radical can be unsubstituted or mono- or up to trisubstituted by the same of different substituents from the group of hydrogen, or Y; a 1-, 2-, 3-, 4-, or 5-pyrrolyl radical, or a 1-, 2-, 3-, 4-, or 5-pyrrolyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 1-, 2-, 3-, 4- or 5-pyrrolyl radical can be unsubstituted or mono- or up to tetrasubstituted by the same or different substituents from the group of hydrogen, or Y; a 1-, 3-, or 5-[1.2.4]-triazolyl radical, or a 1-, 3-, or 5-[1.2.4]-triazolyl-C1-6alkyl radical, different substituents from the group of hydrogen, C1-6 alkyl, halogen or oxo (═O), and the 1-, 3-, or 5-[1.2.4]-triazolyl radical can be unsubstituted or mono- or disubstituted by the same or different substituents from Y; a 1-, 4-, or 5-[1.2.3]-triazolyl radical, or a 1-, 4-, or 5-[1.2.3]-triazolyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of c1-6 alkyl, halogen or oxo (═O), and the 1-, 4-, or 5[1.2.3]-triazolyl radical can be unsubstituted or mono- or disubstituted by the same or different substituents from the group of hydrogen, or Y; a 1- or 5-[1H]-tetrazolyl radical, or a 1-, or 5-[1H]-tetrazolyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 1-, or 5-[1H]-tetrazolyl radical can be unsubstituted or substituted by hydrogen, or Y; a 2- or 5-[2H]-tetrazoyl radical, or a 2- or 5-[2H]-tetrazolyl-C1-6 alkyl radical, where C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 2- or 5-[2H]-tetrazolyl radical can be unsubstituted or substituted by hydrogen, or Y; a 2-, 4-, or 6-[1.3.5]-triazinyl radical, or a 2-, 4-, or 6-[1.3.5]-triazinyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be substituted or mono- or polysubstituted by the same or different substituents from the group of hydrogen, C1-6 alkyl, halogen or oxo (═O), and the 2-, 4-, or 6-[1.3.5]-triazinyl radical can be unsubstituted or mono- or disubstituted by the same or different substituents from the group of hydrogen, or Y; a 2-, 4-, or 5-oxazolyl radical, or a 2-, 4-, or 5-oxazolyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 2-, 4-, or 5-oxazolyl radical can be unsubstituted or mono- or disubstituted by the same or different substituents from the group of hydrogen, or Y; a 3-, 4-, or 5-isoxazolyl radical, or a 3-, 4-, or 5-isoxazolyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 3-, 4-, or 5-isoxazolyl radical can be unsubstituted or mono- or disubstituted by the same or different substituents from the group of hydrogen, or Y; a 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl radical, or a 1-, 2-, 3-, 4-, 5-, 6 or 7-indolyl-C1-6 alkyl radical, wherein the C1-6 alkyl radical can be unsubstituted or mono- or polysubstituted by the same or different substituents from the group of C1-6 alkyl, halogen or oxo (═O), and the 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl radical can be unsubstituted or mono- or up to hexasubstituted by the same or different substituents from the group of hydrogen, or Y.
- 4. The quinoline derivative of claim 3, wherein in R4 said fluorine atoms are trifluoromethyl, and said C1-8 alkoxy is methoxy or ethoxy.
- 5. The quinoline derivative of claim 1, wherein R, R1, R2, R3, X, Z, P, Q, n and m have the meanings given above, and R4 is phenyl which is unsubstituted or substituted by one to five the same or different C1-6 alkoxy groups, where adjacent oxygen atoms can also be linked by C1-2 alkylene groups.
- 6. The quinoline derivative of claim 1, wherein R, R1, R2, R3, X, Z, P, Q, n and m have the meanings given above and R4 is 3,5-dimethoxyphenyl.
- 7. The quinoline derivative of claim 1, wherein R4 has the meanings given above, R, R1, R2, R3 each is hydrogen, Z is an oxygen atom, X is a nitrogen atom, P and Q are each two hydrogen atoms—as in —CH2—, m is zero, and n is 3.
- 8. The quinoline derivative of claim 1, wherein R, R1, R2, R3 are each a hydrogen atom, Z is an oxygen atom, X is a nitrogen atom, P and Q each are two hydrogen atoms as in CH2—, m is zero, n is 3, and R4 is a 3,5-dimethoxyphenyl radical.
- 9. A process far preparing the quinoline derivative of claim 1, which comprises reacting a quinoline carboxylic acid of formula (2)
- 10. The process of claim 9, wherein said leaving group is halogen, hydroxyl, C1-6 alkoxy, —O-tosyl, —O-mesyl, or imidazolyl.
- 11. The process of claim 10, wherein said C1-6 alkoxy is methoxy or ethoxy.
- 12. A therapeutic method for treating tumors in mammals, which comprises administering to a mammal in need therefor at least one quinoline derivative of claim 1 in a tumor treatment effective dose.
- 13. A medicament which comprises as active ingredient at least one quinoline derivative according of claim 1, together with conventional pharmaceutically acceptable auxiliaries, additives and carriers.
- 14. The pharmaceutically acceptable acid addition salt of the quinoline derivative of claim 1, when formed with one of the acids hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acvid, succinic acid, lactic acid, citric acid, acetic acid, tartaric acid, malic acid, maleic acid, embonic acid, malonic acid, trifluoroacetic acid, metanesulfonic acid, and sulfoacetic acid.
Priority Claims (1)
Number |
Date |
Country |
Kind |
100 35 928.0 |
Jul 2000 |
DE |
|
RELATED APPLICATION
[0001] This application is a division of co-pending application Ser. No. 09/910,141 filed Jul. 20, 2001.
Divisions (1)
|
Number |
Date |
Country |
Parent |
09910141 |
Jul 2001 |
US |
Child |
10713859 |
Nov 2003 |
US |