6-BENZYL-2,3,4,7-TETRAHYDRO-INDOLO [2,3-C] QUINOLINE COMPOUNDS USEFUL AS PDE5 INHIBITORS
United States Patent Application
The compounds of formula (I)
wherein R1 to R8 and R11 have the meanings as given in the description, the salts thereof, the N-oxides of the compounds and the salts thereof, and the stereoisomers of the compounds, the salts, the N-oxides of the compounds and the N-oxides of the salts thereof are effective inhibitors of the type 5 phosphodiesterase.
Inventors:
Weinbrenner, Steffen (Konstanz, DE)
Dunkern, Torsten (Volkertshausen, DE)
Marx, Degenhard (Moos, DE)
Schmidt, Beate (Allensbach, DE)
Stengel, Thomas (Konstanz, DE)
Flockerzi, Dieter (Allensbach, DE)
Kautz, Ulrich (Allensbach, DE)
Hauser, Daniela (Singen, DE)
Diefenbach, J?rg (Stockach-Winterspuren, DE)
Christiaans, Johannes A. M. (Lelystad, NL)
Menge, Wiro M. P. B. (Arnhem, NL)
Application Number:
Publication Date:
05/13/2010
Filing Date:
01/30/2008
Export Citation:
NYCOMED GmbH (Konstanz, DE)
Primary Class:
Other Classes:
International Classes:
A61K31/475; A61K31/56; A61P1/16; A61P9/12; A61P11/00; C07D471/04
View Patent Images:
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Related US Applications:
March, 2007Jomard et al.September, 2006Feng et al.August, 2009Shakhov et al.January, 2006MartinJuly, 2007RoszellDecember, 2002Henricus Adan et al.October, 2008Clauzel et al.January, 2007Betz et al.October, 2004Gudmunsson et al.January, 2008BayrockMarch, 2007Avramoff et al.
Attorney, Agent or Firm:
NATH & ASSOCIATES PLLC (112 South West Street, Alexandria, VA, 22314, US)
1. A compound of formula (I)
wherein R1 is selected from the group consisting of
R11 or R1 and R11 combine
R2 is selected from the group consisting of hydrogen and 1-3C- R3 is selected from the group consisting of hydrogen and 1-3C- R4 is selected from the group consisting of hydrogen, halogen, 1-3C-alkoxy, R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy, 1-3C-alkoxy, nitro, amino, —NH—C(O)-1-2C-alkyl, —NH—C(O)—NH2 and a methoxy group substituted by 2 or 3 or R4 and R5 combine to form a group selected from the group consisting of —O—CH2—O—, —O—CH2—CH2— and —CH2—CH2—O—; R6 is selected from the group consisting of
R7 is selected from the group consisting of
R8 is selected from the group consisting of
under the proviso that the compound 6-benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- a salt thereof, an N-oxide of the compound or the salt thereof or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.
2. The compound according to claim 1, wherein R1 is selected from the group consisting of
R11 or R1 and R11 combine
R2 is selected from the group consisting of hydrogen and 1-3C- R3 is selected from the group consisting of hydrogen and 1-3C- R4 is selected from the group consisting of hydrogen, halogen, 1-3C-alkoxy, R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy, 1-3C-alkoxy, nitro, amino, —NH—C(O)-1-2C-alkyl and —NH—C(O)—NH2; R6 is selected from the group consisting of
R7 is selected from the group consisting of
R8 is selected from the group consisting of
under the proviso that the compound 6-benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- a salt thereof, an N-oxide of the compound or the salt thereof or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.
3. The compound according to claim 1, wherein R1 is selected from the group consisting of
R11 or R1 and R11 combine
R2 is selected from the group consisting of hydrogen and 1-3C- R3 is selected from the group consisting of hydrogen and 1-3C- R4 is selected from the group consisting of hydrogen, halogen and 1-3C- R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy and 1-3C- R6 is selected from the group consisting of
R7 is selected from the group consisting of
R8 is selected from the group consisting of
under the proviso that the compound 6-benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- a salt thereof, an N-oxide of the compound or the salt thereof or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.
4. The compound according to claim 1 selected from the group consisting of 6-(4-Methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Methoxy-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-Benzyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Methoxy-benzyl)-3-methyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c] 6-(4-Bromo-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Methoxy-benzyl)-2,3,4,7-tetrahydro-1H-indolo[2,3-c] 6-Benzo[1,3]dioxol-5-ylmethyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Bromo-benzyl)-2,3,4,7-tetrahydro-1H-indolo[2,3-c] 6-(3-Methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 3,3-Dimethyl-6-(4-trifluoromethoxy-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Ethoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 3,3-Dimethyl-6-(3-nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Isopropyl-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3-Chloro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 3,3-Dimethyl-6-(4-nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Methoxy-benzyl)-3-methyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-Benzo[1,3]dioxol-5-ylmethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3-Nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Chloro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3-Bromo-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3,5-Difluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3-Fluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3,4-Difluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 3,3-Dimethyl-6-(4-methyl-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(2-Fluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3-Fluoro-4-methoxy-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3-Fluoro-4-methoxy-benzyl)-2,3,4,7-tetrahydro-1H-indolo[2,3-c] 6-(2,3-Difluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3,5-Difluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(2,3-Dihydro-benzofuran-5-ylmethyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3-Fluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3-Chloro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3-Chloro-5-fluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-Benzo[1,3]dioxol-5-ylmethyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3-Fluoro-4-hydroxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Hydroxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Amino-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one, 6-(3-Amino-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(4-Amino-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- 6-(3-Amino-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1- N-[4-(3,3-Dimethyl-1-oxo-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl]- N-[4-(3,3-Dimethyl-1-oxo-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl]- N-[4-(1-Oxo-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl]- 6-(4-Methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(4-Methoxy-benzyl)-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-Benzyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-Benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(4-Hydroxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 3,3-Dimethyl-6-(4-trifluoromethoxy-benzyl)-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(4-Amino-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(4-Ethoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 3,3-Dimethyl-6-(3-nitro-benzyl)-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(3-Amino-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(4-Isopropyl-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-Benzo[1,3]dioxol-5-ylmethyl-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- N-[4-(1-Hydroxy-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl]- 6-Benzo[1,3]dioxol-5-ylmethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(3-Bromo-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- N-[4-(1-Hydroxy-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl]- 6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(2-Fluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(3,4-Difluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(3,5-Difluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(3-Fluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- N-[4-(1-Hydroxy-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl]- [4-(1-Hydroxy-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl]- 6-(3-Fluoro-4-methoxy-benzyl)-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(3-Amino-benzyl)-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(3,5-Difluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(2,3-Difluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- [4-(3,3-Dimethyl-1-oxo-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl]- [4-(1-Oxo-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl] 6-(4-Methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c] 6-(3-Fluoro-4-hydroxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(2,3-Dihydro-benzofuran-5-ylmethyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(3-Fluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- 6-(3-Chloro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1- and salts thereof, N-oxides of the compounds and the salts thereof and stereoisomers of the compounds, salts, N-oxides of the compounds and N-oxides of the salts thereof.
5. (canceled)
6. A pharmaceutical composition comprising at least one of the compounds, pharmaceutically acceptable salts thereof, N-oxides of the compounds and the salts thereof and stereoisomers of the compounds, salts, N-oxides of the compounds and N-oxides of the salts thereof according to claim 1, together with at least one pharmaceutically acceptable auxiliary.
7. The pharmaceutical composition according to claim 6 further comprising at least one therapeutic agent selected from the group consisting of corticosteroids, anticholinergics, beta-mimetics, lung surfactants, endothelin antagonists, prostacyclins, calcium channel blockers, beta-blockers, type 4 phosphodiesterase inhibitors, antidepressants and antibiotics.
8. (canceled)
9. (canceled)
10. (canceled)
11. (canceled)
12. A method of treating or preventing an acute or chronic airway disease comprising administering to a patient in need thereof a therapeutically effective amount of a compound, pharmaceutically acceptable salt thereof, N-oxide of the compound or the salt thereof or stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof according to claim 1.
13. The method of treating or preventing an acute or chronic airway disease according to claim 12, in which the acute or chronic airway disease is selected from the group consisting of pulmonary hypertension, lung fibrosis, asthma, bronchitis, emphysema and chronic obstructive pulmonary disease.
14. A method of treating or preventing portal hypertension, liver cirrhosis, toxic liver damage, hepatitis, non-alcoholic steatohepatitis or liver fibrosis comprising administering to a patient in need thereof a therapeutically effective amount of a compound, pharmaceutically acceptable salt thereof, N-oxide of the compound or the salt thereof or stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof according to claim 1.
Description:
FIELD OF APPLICATION OF THE INVENTIONThe invention relates to 6-benzyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinoline compounds, which are used in the pharmaceutical industry for the manufacture of pharmaceutical compositions.KNOWN TECHNICAL BACKGROUND6-Benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one is described in Khimiya Geterotsiklicheskikh Soedinenii (3-6 without mentioning any pharmaceutical activity thereof. WO 02/064590 discloses nitrogen-containing heterocyclic PDE5 inhibiting compounds.DESCRIPTION OF THE INVENTIONIt has now been found that the 6-benzyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinoline compounds, which are described in detail below, have surprising and advantageous properties.The invention relates to compounds of formula (I) whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 is selected from the group consisting of hydrogen, halogen, 1-3C-alkoxy,R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy, 1-3C-alkoxy, nitro, amino, —NH—C(O)-1-2C-alkyl, —NH—C(O)—NH2 and a methoxy group substituted by 2 or 3 orR4 and R5 combine to form a group selected from —O—CH2—O—, —O—CH2—CH2— and —CH2—CH2—O—;R6 is selected from the group consisting of R7 is selected from the group consisting of R8 is selected from the group consisting of
under the proviso that the compound 6-benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.1-3C-Alkyl is a straight-chain or branched alkyl group having 1 to 3 carbon atoms. Examples are methyl, ethyl, n-propyl and iso-propyl.Halogen includes fluorine, chlorine, bromine and iodine, with fluorine, chlorine and bromine being preferred.1-3C-Alkoxy represents a group which, in addition to the oxygen atom, contains a straight-chain or branched alkyl radical having 1 to 3 carbon atoms. Examples are the methoxy, ethoxy, n-propoxy and iso-propoxy group.The group —NH—C(O)-1-2C-alkyl is selected from —NH—C(O)—CH3 and —NH—C(O)—C2H5.The methoxy group substituted by 2 or 3 fluorine atoms represents a group selected from a difluoromethoxy group and a trifluoromethoxy group.The nitro group represents the moiety —NO2, the amino group represents the moiety —NH2 and the oxo group represents the moiety ═O.In a preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 is selected from the group consisting of hydrogen, halogen, 1-3C-alkoxy,R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy, 1-3C-alkoxy, nitro, amino, —NH—C(O)-1-2C-alkyl, —NH—C(O)—NH2 and a methoxy group substituted by 2 or 3 orR4 and R5 combine to form a group selected from —O—CH2—O—, —O—CH2—CH2— and —CH2—CH2—O—;R6 is selected from the group consisting of R7 is selected from the group consisting of R8 is selected from the group consisting of
under the proviso that at least one of substituents R1 to R8 and R11 under the proviso that the compound 6-benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 is selected from the group consisting of hydrogen, halogen, 1-3C-alkoxy,R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy, 1-3C-alkoxy, nitro, amino, —NH—C(O)-1-2C-alkyl, —NH—C(O)—NH2 and a methoxy group substituted by 2 or 3 orR4 and R5 combine to form a group selected from —O—CH2—O—, —O—CH2—CH2— and —CH2—CH2—O—;R6 is selected from the group consisting of R7 is selected from the group consisting of R8 is selected from the group consisting of under the proviso that at least two of substituents R1 to R8 and R11under the proviso that the compound 6-benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 is selected from the group consisting of hydrogen, halogen, 1-3C-alkoxy,R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy, 1-3C-alkoxy, nitro, amino, —NH—C(O)-1-2C-alkyl, —NH—C(O)—NH2 and a methoxy group substituted by 2 or 3 orR4 and R5 combine to form a group selected from —O—CH2—O—, —O—CH2—CH2— and —CH2—CH2—O—;R6 is selected from the group consisting of R7 is selected from the group consisting of R8 is selected from the group consisting of
under the proviso that at least one of substituents R4 to R8
a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 is selected from the group consisting of hydrogen, halogen, 1-3C-alkoxy,R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy, 1-3C-alkoxy, nitro, amino, —NH—C(O)-1-2C-alkyl, —NH—C(O)—NH2 and a methoxy group substituted by 2 or 3 orR4 and R5 combine to form a group selected from —O—CH2—O—, —O—CH2—CH2— and —CH2—CH2—O—;R6 is selected from the group consisting of R7 is selected from the group consisting of R8 is selected from the group consisting of under the proviso that at least two of substituents R4 to R8a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1R11R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 is selected from the group consisting of hydrogen, halogen, 1-3C-alkoxy,R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy, 1-3C-alkoxy, nitro, amino, —NH—C(O)-1-2C-alkyl, —NH—C(O)—NH2 and a methoxy group substituted by 2 or 3 orR4 and R5 combine to form a group selected from —O—CH2—O—, —O—CH2—CH2— and —CH2—CH2—O—;R6 is selected from the group consisting of R7 is selected from the group consisting of R8 is selected from the group consisting of a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 is selected from the group consisting of hydrogen, halogen, 1-3C-alkoxy,R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy, 1-3C-alkoxy, nitro, amino, —NH—C(O)-1-2C-alkyl, —NH—C(O)—NH2 and a methoxy group substituted by 2 or 3 orR4 and R5 combine to form a group selected from —O—CH2—O—, —O—CH2—CH2— and —CH2—CH2—O—;R6 is selected from the group consisting of R7 is selected from the group consisting of R8 is selected from the group consisting of
under the proviso that the compound 6-benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1R11R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 is selected from the group consisting of hydrogen, halogen, 1-3C-alkoxy,R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy, 1-3C-alkoxy, nitro, amino, —NH—C(O)-1-2C-alkyl, —NH—C(O)—NH2 and a methoxy group substituted by 2 or 3 orR4 and R5 combine to form a group selected from —O—CH2—O—, —O—CH2—CH2— and —CH2—CH2—O—;R6 is selected from the group consisting of R7 is selected from the group consisting of R8 is selected from the group consisting of a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 is selected from the group consisting of hydrogen, halogen, 1-3C-alkoxy,R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy, 1-3C-alkoxy, nitro, amino, —NH—C(O)-1-2C-alkyl and —NH—C(O)—NH2;R6 is selected from the group consisting of R7 is selected from the group consisting of R8 is selected from the group consisting of
under the proviso that the compound 6-benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-a salt thereof, an N-oxide of the compound or the salt thereof or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 is selected from the group consisting of hydrogen, halogen and 1-3C-R5 is selected from the group consisting of hydrogen, halogen, 1-3C-alkyl, hydroxy and 1-3C-R6 is selected from the group consisting of R7 is selected from the group consisting of R8 is selected from the group consisting of
under the proviso that the compound 6-benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-a salt thereof, an N-oxide of the compound or the salt thereof or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 is selected from the group consisting of R5 is selected from the group consisting of hydrogen, hydroxy and 1-3C-R6 is selected from the group consisting of R7 is selected from the group consisting of R8under the proviso that the compound 6-benzyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-a salt thereof, an N-oxide of the compound or the salt thereof or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting ofR3 is selected from the group consisting ofR4 is selected from the group consisting of hR5R6 is selected from the group consisting of hR7 is selected from the group consisting of hR8a salt thereof, an N-oxide of the compound or the salt thereof or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4R5R6R7R8a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4R5 is 1-3C-R6R7R8a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4R5 is 1-3C-R6R7R8a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.In a further preferred embodiment, the invention relates to compounds of formula (I), whereinR1 is selected from the group consisting of R11 orR1 and R11 combine R2 is selected from the group consisting of hydrogen and 1-3C-R3 is selected from the group consisting of hydrogen and 1-3C-R4 and R5 combine to form a group selected from —O—CH2—O—, —O—CH2—CH2— and —CH2—CH2—O—;R6 is selected from the group consisting of R7 is selected from the group consisting of R8 is selected from the group consisting of a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof.It is to be understood that the invention covers all combinations of substituent groups referred to hereinabove. In particular, the invention covers all combinations of preferred groups described herein.Salts of the compounds according to the invention, the N-oxides thereof, the stereoisomers of the salts and the N-oxides thereof include all inorganic and organic acid addition salts and salts with bases, especially all pharmaceutically acceptable inorganic and organic acid addition salts and salts with bases, particularly all pharmaceutically acceptable inorganic and organic acid addition salts and salts with bases customarily used in pharmacy.Examples of acid addition salts include, but are not limited to, hydrochlorides, hydrobromides, phosphates, nitrates, sulfates, acetates, trifluoroacetates, citrates, D-gluconates, benzoates, 2-(4-hydroxybenzoyl)benzoates, butyrates, sulfosalicylates, maleates, laurates, malates, lactates, fumarates, succinates, oxalates, tartarates, stearates, benzenesulfonates (besilates), toluenesulfonates (tosilates), methanesulfonates (mesilates), laurylsulfonates, 3-hydroxy-2-naphthoates, lactobionates, galactarates, pyroglutamates, embonates and ascorbates. Hydrochlorides, succinates, malates and pyroglutamates of the compounds according to the invention are preferred.Examples of salts with bases include, but are not limited to, lithium, sodium, potassium, calcium, aluminum, magnesium, titanium, ammonium, meglumine and guanidinium salts.The salts include water-insoluble and, particularly, water-soluble salts.The compounds according to the invention, the salts thereof, the N-oxides of the compounds and the salts thereof and the stereoisomers of the compounds, salts, N-oxides of the compounds and N-oxides of the salts thereof may contain, e.g. when isolated in crystalline form, varying amounts of solvents. Included within the scope of the invention are, therefore, all solvates of the compounds of formula (I), the salts thereof, the N-oxides of the compounds and the salts thereof and the stereoisomers of the compounds, salts, N-oxides of the compounds and N-oxides of the salts thereof. Hydrates are a preferred example of said solvates.The N-oxides of the compounds according to the invention, the salts thereof, the stereoisomers of the compounds and the salts thereof include compounds, wherein the nitrogen atom of the pyridine moiety is oxidized, as illustrated by formula (Ia) below: The compounds according to the invention, the salts thereof, the N-oxides of the compounds and the salts thereof include stereoisomers. In case R1 being a hydroxy group, R11 being hydrogen and R2 and R3 representing identical groups, the compounds according to the invention, the salts thereof, the N-oxides of the compounds and the salts thereof have one stereogenic center. In case R1 and R11 being hydrogen or R1 and R11 combining to form an oxo group and R2 and R3 representing different groups, the compounds according to the invention, the salts thereof, the N-oxides of the compounds and the salts thereof have one stereogenic center. In case R1 being a hydroxy group, R11 being hydrogen and R2 and R3 representing different groups, the compounds according to the invention, the salts thereof, the N-oxides of the compounds and the salts thereof have two stereogenic centers. Each of said stereogenic centers may have the absolute configuration R or the absolute configuration S (according to the rules of Cahn, Ingold and Prelog). Accordingly, the stereoisomers (1R), (1S), (3R), (3S), (1R,3R), (1R,3S), (1S,3R) and (1S,3S), wherein the numbers refer to the atoms indicated in formula (Ib) below the salts thereof, the N-oxides of the stereoisomers and the salts thereof are part of the invention.In a preferred embodiment, the invention relates to stereoisomers of formula (Ib) having the configuration (1R) or (1S), with the carbon atom at position number 3 not being an asymmetric carbon atom.The invention further includes all mixtures of the stereoisomers mentioned above independent of the ratio, including the racemates.Some of the compounds, salts thereof, N-oxides of the compounds and the salts thereof, stereoisomers of the compounds, salts, N-oxides of the compounds and N-oxides of the salts thereof according to the invention may exist in different crystalline forms (polymorphs) which are within the scope of the invention.Furthermore, derivatives of the compounds of formula (I), the salts thereof, the N-oxides of the compounds or the salts thereof, stereoisomers of the compounds, salts, N-oxides of the compounds or N-oxides of the salts thereof which are converted into compound (I) or a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof in a biological system (bioprecursors or pro-drugs) are covered by the invention. Said biological system is e.g. a mammalian organism, particularly a human subject. The bioprecursor is, for example, converted into the compound of formula (I), a salt thereof, an N-oxide of the compound or the salt thereof, or a stereoisomer of the compound, the salt, the N-oxide of the compound or the N-oxide of the salt thereof by metabolic processes.The compounds according to the invention can be prepared as follows.As shown in reaction scheme 1, a compound of formula (Ic) wherein R1 and R11 combine to form an oxo group can be obtained by reacting a compound of formula (II) with ammonia in an appropriate solvent, e.g. acetonitrile, preferably under microwave heating. The compound of formula (II) can be prepared by cyclization of a compound of formula (IV) with a compound of formula (III) in the presence of a strong inorganic acid, e.g. perchloric acid, in a suitable solvent, e.g. nitromethane.Compounds of formula (III) are commercially available or can be obtained according to procedures known in the art. In an alternative procedure, as illustrated in reaction scheme 2, a compound of formula (IV) can be reacted with a compound of formula (VI), in which X is a suitable leaving group, e.g. halogen, such as chlorine, or a conjugate base of an acid, such as trifluoroacetate, in a Friedel-Crafts acylation reaction in the presence of an appropriate Lewis acid, e.g. zinc chloride, boron trifluoride etherate or orthophosphoric acid, in a suitable solvent, e.g. dichloromethane, dichloroethane, diethylether, toluene and/or chlorobenzene, to give the corresponding compound of formula (II) or (V) or a mixture thereof. Said Friedel-Crafts acylation reaction can be based on, for example, Duval et al. (2004) Tetrahedron Letters 45: . The compound of formula (II) or (V) or the mixture thereof can be subjected to a cyclization condensation reaction with ammonium acetate in an appropriate solvent, e.g. acetic acid, preferably at elevated temperature, or a cyclization condensation reaction with ammonia in an appropriate solvent, e.g. methanol, preferably at elevated temperature, to give a corresponding compound of formula (Ic). In some cases it may be convenient to perform both the Friedel-Crafts acylation reaction and the cyclization condensation reaction in one pot.Compounds of formula (VI) are commercially available or can be obtained according to procedures known in the art. As shown in reaction scheme 3, compounds of formula (IV) are obtainable via an aldol-type condensation of compounds of formula (VIII), in which PG stands for a suitable temporary protecting group, e.g. acetyl, with compounds of formula (VII), and subsequent removal of PG. Compounds of formulae (VIII) and (VII) are commercially available or can be obtained according to procedures known in the art.Furthermore, a compound of formula (Id), in which R1 and R11 are hydrogen, can be obtained as shown in reaction scheme 4. In particular, a compound of formula (XI) can be reacted with a compound of formula (X) in an art-known nucleophilic substitution reaction [see e.g. Heterocycles 31 (8),
(1990)]. The thus obtained hydroxy-compound can be oxidized in a manner known to the skilled person, e.g. according to a Swern oxidation [see e.g. Tetrahedron 47 (41) ] to give the corresponding compound of formula (IX). The compound of formula (IX) can be reacted according to reaction scheme 1 or 2 [replacing compound (IV)] to give a compound of formula (Id). The procedure as shown in reaction scheme 4 is preferably used in synthesizing compounds of formula (Id) wherein each of R1, R11, R2 and R3 represents hydrogen. The compounds of formulae (X) and (XI) are known, commercially available or can be obtained according to known procedures.In particular, a compound of formula (Ie), in which R1, R11, R2 and R3 are hydrogen, can also be obtained by a condensation reaction as shown in reaction scheme 5. A compound of formula (XI) is, for example, reacted with a compound of formula (XIII) in the presence of acetic acid and H3PO4, preferably at elevated temperature. Compound (XIV) thus obtained can be reacted according to reaction scheme 1 or 2 [replacing compound (IV)] to give a compound of formula (Ie). The compounds of formulae (XI) and (XIII) are known, commercially available or can be obtained according to known procedures.Alternatively, a compound of formula (Id), in which R1 and R11 are hydrogen can be obtained as illustrated in reaction scheme 6. In a first step, a compound of formula (XI) is reacted with a compound of formula (XII) in an art-known radicalic substitution reaction [see e.g. JACS 126, )]. The thus obtained compound of formula (IX) can be reacted according to reaction scheme 1 or 2 [replacing compound (IV)] to give a compound of formula (Id). The method shown in reaction scheme 6 is preferably used in preparing compounds of formula (Id) in which each of R1, R11 and R2 is hydrogen and R3 is 1-3C-alkyl. Compounds of formulae (XII) are known, commercially available or can be obtained according to known procedures.Compounds of formula (I) can be converted into different compounds of formula (I) by methods known in the art. For example,
a compound of formula (I), wherein R1 is hydroxy and R11 is hydrogen, can be prepared from a compound of formula (I), wherein R1 and R11 combine to form an oxo group, by reduction reaction, e.g. with the aid of a suitable reduction agent, such aa compound of formula (I), wherein R1 and R11 are hydrogen, can be prepared from a compound of formula (I), wherein R1 and R11 combine to form an oxo group, by reduction reaction, e.g. with the aid of a suitable reduction agent, such as hydrazine (e.g. according to a Wolff-Kishner reduction);a compound of formula (I), wherein R4 and/or R5 represent(s) a nitro group can be converted into the corresponding amino compound by reduction reaction, e.g. with the aid of a suitable reduction agent, such as tin dichloride or hydrogen gas and a palladiua compound of formula (I), wherein R5 represents a group —NH—C(O)-1-2C-alkyl can be prepared e.g. from a compound of formula (I), wherein R5 represents an amino group by reaction with an appropriate carboxylic acid chloride or carboxylic anhydride, in the presence of a base, e.g. triethylamine, pyridine or potassium carbonate, or with an appropriate carboxylic acid in the presence of a dehydrating agent, e.g. dicya compound of formula (I), wherein R5 represents —NH—C(O)—NH2 can be obtained e.g. from a compound of formula (I), wherein R5 represents an amino group by reaction with potassium cyanate in the presence of a mineral acid, such as hydrochloric acid, or by coa compound of formula (I), wherein R5 is hydroxy can be synthesized e.g. from a compound of formula (I), wherein R5 is 1-3C-alkoxy by dealkylation with a Lewis acid, such as boron tribromide.
It is known to the person skilled in the art that, if there are a number of reactive centers on a starting or intermediate compound, it may be necessary to block one or more reactive centers temporarily by protective groups in order to allow a reaction to proceed specifically at the desired reaction center.The compounds according to the invention are isolated and purified in a manner known per se, e.g. by distilling off the solvent in vacuo and recrystallizing the residue obtained from a suitable solvent or subjecting it to one of the customary purification methods, such as column chromatography on a suitable support material.Salts of the compounds of formula (I), the N-oxides thereof and the stereoisomers of the compounds and the N-oxides thereof according to the invention can be obtained by dissolving the free compound in a suitable solvent (for example a ketone such as acetone, methylethylketone or methylisobutylketone, an ether such as diethyl ether, tetrahydrofurane or dioxane, a chlorinated hydrocarbon such as methylene chloride or chloroform, a low molecular weight aliphatic alcohol such as methanol, ethanol or isopropanol, a low molecular weight aliphatic ester such as ethyl acetate or isopropyl acetate, or water) which contains the desired acid or base, or to which the desired acid or base is then added. The acid or base can be employed in salt preparation, depending on whether a mono- or polybasic acid or base is concerned and depending on which salt is desired, in an equimolar quantitative ratio or one differing therefrom. The salts are obtained by filtering, reprecipitating, precipitating with a non-solvent for the salt or by evaporating the solvent. Salts obtained can be converted into the free compounds which, in turn, can be converted into salts. In this manner, pharmaceutically unacceptable salts, which can be obtained, for example, as process products in the manufacturing on an industrial scale, can be converted into pharmaceutically acceptable salts by processes known to the person skilled in the art.The compounds of formula (I), the salts thereof and the stereoisomers of the compounds and the salts according to the invention can be converted into their N-oxides, for example, by reaction with peracids, such as m-chloroperbenzoic acid or peracetic acid. The person skilled in the art is familiar with the reaction conditions for carrying out the N-oxidation.Pure diastereomers and pure enantiomers of the compounds of formula (I), the salts thereof, the N-oxides of the compounds and the N-oxides of the salts according to the invention can be obtained e.g. by asymmetric synthesis, by using chiral starting compounds in synthesis and/or by splitting up enantiomeric and diasteriomeric mixtures obtained in synthesis. Preferably, the pure diastereomeric and pure enantiomeric compounds of the invention are obtainable by asymmetric synthesis and/or by using chiral starting compounds in synthesis.In particular, for example the (1S)-enantiomers of the compounds of formula (I), the salts thereof, the N-oxides of the compounds and the salts thereof according to the invention can be obtained by reduction of the corresponding ketone precursors (wherein R1 and R11 combine to form an oxo group) with sodium borohydride in the presence of (4S,5S)-2-(3-nitro-phenyl)-[1,3,2]dioxaborolane-4,5-dicarboxylic acid, which can be prepared by esterification of 3-nitrophenyl boronic acid and D-tartaric acid in the presence of a dehydrating agent such as calcium hydride. Likewise, for example the (1R)-enantiomers of the compounds of formula (I), the salts thereof, the N-oxides of the compounds and the salts thereof according to the invention can be obtained using (4R,5R)-2-(3-nitro-phenyl)-[1,3,2]dioxaborolane-4,5-dicarboxylic acid, which can be prepared by esterification of 3-nitrophenyl boronic acid and L-tartaric acid in the presence of a dehydrating agent such as calcium hydride.Enantiomeric and diastereomeric mixtures can be split up into the pure enantiomers and pure diastereomers by methods known to a person skilled in the art. Preferably, diastereomeric mixtures are separated by crystallization, in particular fractional crystallization, or chromatography. Enantiomeric mixtures can be separated e.g. by forming diastereomers with a chiral auxiliary agent, resolving the diastereomers obtained and removing the chiral auxiliary agent. As chiral auxiliary agents, for example, chiral acids can be used to separate enantiomeric bases and chiral bases can be used to separate enantiomeric acids via formation of diastereomeric salts. Furthermore, diastereomeric derivatives such as diastereomeric esters can be formed from enantiomeric mixtures of alcohols or enantiomeric mixtures of acids, respectively, using chiral acids or chiral alcohols, respectively, as chiral auxiliary agents. Additionally, diastereomeric complexes or diastereomeric clathrates may be used for separating enantiomeric mixtures. Alternatively, enantiomeric mixtures can be split up using chiral separating columns in chromatography. Another suitable method for the isolation of enantiomers is the enzymatic separation.As will be appreciated by persons skilled in the art, the invention is not limited to the particular embodiments described herein, but covers all modifications of said embodiments that are within the spirit and scope of the invention as defined by the appended claims.All patents, patent applications, publications, test methods and other materials cited herein are incorporated by reference in their entireties.The following examples illustrate the invention in greater detail, without restricting it. Further compounds according to the invention, of which the preparation is not explicitly described, can be prepared in an analogous way.The compounds which are mentioned in the examples, the salts thereof, N-oxides of the compounds and the salts thereof and stereoisomers of the compounds, salts, N-oxides of the compounds and N-oxides of the salts thereof represent preferred embodiments of the invention.EXAMPLESThe following abbreviations are used: min: minutes, h: hour(s), DCM: dichloromethane, DCE: dichloroethane, THF: tetrahydrofurane, EA: ethyl acetate, mp.: melting point, RT: room temperature (20 to 25° C.), TLC: thin layer chromatography, MS: mass spectrometry, 1H-NMR: 1H nuclear magnetic resonance spectroscopy.Final Compounds1. 6-(4-Methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStep 1: 5.08 g of 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1) and 62.55 g of 4-methoxyphenyl acetic acid anhydride are solved in 150 ml nitromethane. The resulting solution is treated 6 times (every 10 minutes) with 0.2 ml of a 70% (v/v) aqueous HClO4 solution and stirred for one additional hour. The reaction mixture is diluted with 100 ml dichloromethane and 50 ml saturated aqueous NaCO3 solution. The organic layer is separated and the aqueous layer is extracted again. The combined organic extracts are dried and crystallized from nitromethane to give 4.65 g 6-(4-methoxy-benzylidene)-3,3-dimethyl-3,4,6,7-tetrahydro-2H-5-oxa-7-aza-benzo[c]fluoren-1-one.1H-NMR (200 MHz, CDCl3): δ=1.17 (s, 6H), 2.46 (s, 2H), 2.63 (s, 2H), 3.85 (s, 3H), 6.0 (s, 1H), 6.92-6.96 (m, 2H), 7.14-7.32 (m, 3H), 7.56-7.62 (m, 2H), 8.07 (br, 1H), 8.81 (d, J=7.5 Hz, 1H)Step 2: 200 mg of 6-(4-methoxy-benzylidene)-3,3-dimethyl-3,4,6,7-tetrahydro-2H-5-oxa-7-aza-benzo[c]fluoren-1-one is suspended in 10 ml acetonitrile and treated with 10 ml 25% (w/v) aqueous NH3 solution. The reaction mixture is heated in a sealed vial by microwave heating (130° C.) for 25 min. The solvent is removed and the residue is dissolved in dichloromethane and water. After separation of the organic layer, the aqueous layer is extracted with dichloromethane, the combined organic layers are dried and evaporated to dryness. The residue is purified by flash chromatography to give 134 mg of the title compound.1H-NMR (200 MHz, CDCl3): δ=1.19 (s, 6H), 2.71 (s, 2H), 3.24 (s, 2H), 3.77 (s, 3H), 4.50 (s, 2H), 6.82-6.88 (m, 2H), 7.19-7.34 (m, 4H), 7.99 (br, 1H), 9.34 (d, J=8.3 Hz, 1H)mp.: 169° C.Alternative Procedure:Step 1: 10 g p-methoxyphenylacetylchloride is dissolved in 200 ml dry DCM. To this solution is added 7.4 g ZnCl2 and 4.6 g 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1). 25 ml of diethyl ether are added to dissolve the occurred slurry, followed by stirring for 2 h at room temperature. The reaction mixture is poured into ice-cold 1M HCl solution and the product is extracted with DCM. The organic layer is washed with 2×25 ml water and 2×25 ml saturated sodium bicarbonate solution. The organic layer is dried over MgSO4, filtered and evaporated. The crude 3-hydroxy-2-{2-[2-(4-methoxy-phenyl)-ethanoyl]-1H-indol-3-yl}-5,5-dimethylcyclohex-2-enone thus obtained is used immediately without further purification in the next step. Step 2: The crude 3-hydroxy-2-{2-[2-(4-methoxy-phenyl)-ethanoyl]-1H-indol-3-yl}-5,5-dimethyl-cyclohex-2-enone is dissolved in 100 ml acetic acid and 27.8 g ammonium acetate is added. The mixture is stirred for 2 h at 90° C. The acetic acid is evaporated. 100 ml ethyl acetate and 200 ml saturated sodium bicarbonate solution are added and separated. The organic layer is washed with 100 ml saturated sodium bicarbonate solution, dried with MgSO4 and evaporated. The product is purified by chromatography with an eluens system of petroleum ether/ethyl acetate (2/1 v/v) with 2% (v/v) triethylamine. The obtained oil is crystallized from a diethyl ether/HCl solution to yield 3.6 g of the HCl salt.The following compounds are obtained by using the first described procedure of Example 1 analogously.2. 6-(4-Methoxy-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3-Hydroxy-2-(1H-indol-3-yl)-cyclohex-2-enone (compound A3) and 4-methoxyphenyl acetic acid anhydride1H-NMR (200 MHz, CDCl3): δ=2.20-2.33 (m, 2H), 2.86 (t, J=6.1 Hz, 2H), 3.38 (t, J=6.2 Hz, 2H), 3.74 (s, 3H), 4.57 (s, 2H), 6.77-6.83 (m, 2H), 7.23-7.32 (m, 3H), 7.38-7.42 (m, 1H), 7.50-7.61 (m, 1H), 8.52 (br, 1H), 9.31 (d, J=8.3 Hz, 1H)mp.: 177° C.3. 6-Benzyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3-Hydroxy-2-(1H-indol-3-yl)-cyclohex-2-enone (compound A3) and phenyl acetic acid anhydride1H-NMR (200 MHz, DB-DMSO): δ=2.10-2.16 (m, 2H), 2.77 (t, J=6.1 Hz, 2H), 3.19 (t, J=6.2 Hz, 2H), 4.52 (s, 2H), 7.13-7.31 (m, 4H), 7.35-7.39 (m, 2H), 7.54-7.66 (m, 2h), 9.21 (d, J=8.4 Hz, 1H), 12.0 (br, 1H)mp.: 205° C.4. 6-(4-Methoxy-benzyl)-3-methyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolineStarting compounds: 2-(1H-Indol-3-yl)-5-methyl-cyclohexanone (compound A5) and 4-methoxy-phenyl acetic acid anhydride1H-NMR (400 MHz, d6-DMSO): δ=1.10 (d, J=6.5 Hz, 3H), 1.45-1.55 (m, 1H), 1.97-2.07 (m, 2H), 2.54-2.61 (m, 1H), 3.02 (dd, J=16.4, J=4 Hz, 1H), 3.15-3.23 (m, 1H), 3.36-3.40 (m, 1H), 3.66 (s, 3H), 4.35 (s, 2H), 6.81 (d, J=8.7 Hz, 2H), 7.19-7.23 (m, 1H), 7.28 (d, J=8.7 Hz, 2H), 7.50-7.54 (m, 1H), 7.60 (d, J=8.2 Hz, 1H), 8.14 (d, J=8 Hz, 1H), 11.60 (br, 1H)mp.: 186° C.The following compounds are obtained by using the second described procedure of Example 1 analogously.5. 6-(4-Bromo-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one, HCl saltStarting compounds: 4-bromo-phenylacetylchloride and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)1H-NMR (200 MHz, CDCl3): δ=1.16 (s, 6H), 2.71 (s, 2H), 3.51 (s, 2H), 5.16 (s, 2H), 6.95-6.99 (m, 2H), 7.32-7.40 (m, 1H), 7.63-7.75 (m, 3H), 7.99 (d, J=8.3 Hz, 1H), 9.26 (d, J=8.5 Hz, 1H), 13.27 (bs, 1H), 15.33 (bs, 1H)mp.: 244-245° C.6. 6-(4-Methoxy-benzyl)-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinoline, HCl saltStarting compounds: 4-methoxy-phenylacetylchloride and 2-(1H-indol-3-yl)-cyclohexanone (compound A4)mp.: decomposes at 231° C.7. 6-Benzo[1,3]dioxol-5-ylmethyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one, HCl saltStarting compounds: Benzo[1,3]dioxol-5-yl-acetylchloride and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: decomposes at 200° C.8. 3,3-Dimethyl-6-(4-nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one, HCl saltStarting compounds: 4-nitro-phenylacetylchloride and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 214-215° C.9. 6-(4-Bromo-benzyl)-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinoline, HCl saltStarting compounds: 4-bromo-phenylacetylchloride and 2-(1H-indol-3-yl)-cyclohexanone (compound A4)mp.: 311-312° C.10. 6-(3-Methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneIn a 20 ml microwave vial, 0.57 g 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1) is suspended in 2 ml DCE and 5 ml of a 1M ZnCl2 solution in ether is added. To this solution, 0.92 g 3-methoxy-phenylacetylchloride dissolved in 2 ml dry DCE is added and stirred for 2 h at room temperature. Slowly, 5 ml of a 7N NH3 solution in methanol is added and the mixture is heated in a Biotage Initiator microwave reactor for 30 min at 150° C. The mixture is diluted with 25 ml ethyl acetate and 20 ml 2M aqueous NH3. The organic layer is washed with brine (saturated sodium chloride solution), dried over MgSO4, filtered and concentrated in vacuo. The product is purified by chromatography [Silicagel, petroleum ether/ethyl acetate (3/1 v/v)] and crystallized from ethyl acetate/diethyl ether to yield 0.37 g of the title compound.1H-NMR (200 MHz, CDCl3): δ=1.17 (s, 6H), 2.76 (s, 2H), 3.26 (s, 2H), 3.72 (s, 3H), 4.55 (s, 2H), 6.70-6.95 (m, 3H), 7.15-7.40 (m, 3H), 7.51 (t, J=7.0 Hz, 1H), 8.10 (br s, 1H), 9.31 (d, J=8.4 Hz, 1H) MS (MH+ found)=385.3The following compounds are obtained by using the procedure of Example 10 analogously:11. 3,3-Dimethyl-6-(4-trifluoromethoxy-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 4-Trifluoromethoxy-phenylacetylchloride and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 141-143° C.MS (MH+ found)=439.412. 6-(4-Ethoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 4-Ethoxy-phenylacetylchloride and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 179-181° C.MS (MH+ found)=399.413. 3,3-Dimethyl-6-(3-nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3-Nitro-phenylacetylchloride and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: decomposes at 236° C.MS (MH+ found)=400.314. 6-(4-Isopropyl-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 4-Isopropyl-phenylacetylchloride and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 153-155° C.MS (MH+ found)=397.415. 6-(3-Chloro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3-Chloro-4-methoxy-phenylacetylchloride and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 209-211° C.MS (MH+ found)=419.316. 3,3-Dimethyl-6-(4-nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 4-Nitro-phenylacetylchloride and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-e none (compound A1)mp.: 164-166° C.17. 6-(4-Methoxy-benzyl)-3-methyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 4-Methoxy-phenylacetylchloride and 3-hydroxy-2-(1H-indol-3-yl)-5-methyl-cyclohex-2-enone (compound A2)mp.: 102° C.MS (MH+ found)=371.318. 6-Benzo[1,3]dioxol-5-ylmethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: Benzo[1,3]-dioxol-5-yl-acetyl chloride and 3-hydroxy-2-(1H-indol-3-yl)-cyclohex-2-enone (compound A3)mp.: 194-197° C.MS (MH+ found)=371.319. 6-(3-Nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3-Nitro-phenylacetylchloride and 3-hydroxy-2-(1H-indol-3-yl)-cyclohex-2-enone (compound A3)mp.: decomposes at 221° C.MS (MH+ found)=372.320. 6-(4-Chloro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one1.36 g 4-chlorophenylacetic acid is stirred with 1.1 ml trifluoroacetic anhydride at RT, after 15 min the solution is diluted with 3 ml DCE and added to a cooled solution of 1.02 g 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1) in 3 ml DCE and 8 ml of a 1M ZnCl2 solution in ether. The mixture is stirred at RT for 1 h. 6 ml of a 7N NH3 solution in methanol is added slowly and the mixture is heated at 80° C. for 17 h. The mixture is cooled to RT and 25 ml EA and 20 ml 2M ammonia are added. The organic layer is separated, dried with MgSO4 and concentrated in vacuo. The product is purified by chromatography [Silicagel, petroleum ether/ethyl acetate (3/1 v/v)] and crystallized from ethyl acetate/diethyl ether to yield 0.45 g of the title compound.mp.: 205-207° C.MS (MH+ found)=389.3The following compounds are obtained by using the procedure of Example 20 analogously:21. 6-(3-Bromo-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3-Bromophenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 215-219° C.MS (MH+ found)=433.3 and 435.322. 6-(3,5-Difluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3,5-Difluorophenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 204-208° C.MS (MH+ found)=391.323. 6-(3-Fluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3-Fluoro-4-methoxy-phenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 192-195° C.MS (MH+ found)=403.324. 6-(3,4-Difluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3,4-Difluorophenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 204-207° C.MS (MH+ found)=391.325. 3,3-Dimethyl-6-(4-methyl-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 4-Methylphenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 182-184° C.MS (MH+ found)=369.426. 6-(4-Nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 4-Nitrophenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-cyclohex-2-enone (compound A3)mp.: 138-140° C.MS (MH+ found)=372.227. 6-(2-Fluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 2-Fluoro-4-methoxy-phenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 138-140° C.MS (MH+ found)=403.328. 6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 4-Fluorophenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 200-204° C.MS (MH+ found)=373.429. 6-(3-Fluoro-4-methoxy-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3-Fluoro-4-methoxy-phenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-cyclohex-2-enone (compound A3)mp.: 228-230° C.MS (MH+ found)=375.330. 6-(3-Fluoro-4-methoxy-benzyl)-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolineStarting compounds: 3-Fluoro-4-methoxy-phenylacetic acid and 2-(1H-indol-3-yl)-cyclohexanone (compound A4)mp.: 118-120° C.MS (MH+ found)=361.331. 6-(2,3-Difluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 2,3-Difluoro-4-methoxy-phenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 199-200° C.MS (MH+ found)=421.432. 6-(3,5-Difluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3,5-Difluoro-4-methoxy-phenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)mp.: 195-196° C.MS (MH+ found)=421.433. 6-(2,3-Dihydro-benzofuran-5-ylmethyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compound: (2,3-Dihydro-benzofuran-5-yl)-acetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)34. 6-(3-Fluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3-Fluorophenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)1H-NMR (300 MHz, d6-DMSO): δ=1.08 (s, 6H), 2.67 (s, 2H), 3.14 (s, 2H), 4.55 (s, 2H), 6.98-7.08 (m, 1H), 7.18-7.38 (m, 4H), 7.56-7.69 (m, 2H), 9.23 (d, J=8.3 Hz, 1H), 12.00 (s, 1H)m.p.: 184-192° C. (dec.)35. 6-(3-Chloro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3-Chlorophenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)1H-NMR (300 MHz, d6-DMSO): δ=1.08 (s, 6H), 2.67 (s, 2H), 3.13 (s, 2H), 4.54 (s, 2H), 7.20-7.35 (m, 4H), 7.46 (s, 1H), 7.55-7.67 (m, 2H), 9.23 (d, J=8.4 Hz, 1H), 12.00 (br, 1H)m.p.: 206-209° C.36. 6-(3-Chloro-5-fluoro-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: 3-Chloro-5-fluorophenylacetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)1H-NMR (300 MHz, d6-DMSO): δ=1.09 (s, 6H), 2.68 (s, 2H), 3.14 (s, 2H), 4.55 (s, 2H), 7.19-7.35 (m, 4H), 7.56-7.69 (m, 2H), 9.23 (d, J=8.3 Hz, 1H), 12.00 (br, 1H)m.p.: 219-221° C.37. 6-Benzo[1,3]dioxol-5-ylmethyl-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compounds: Benzo[1,3]dioxol-5-yl-acetic acid and 3-hydroxy-2-(1H-indol-3-yl)-5,5-dimethyl-cyclohex-2-enone (compound A1)1H-NMR (300 MHz, d6-DMSO): δ=1.09 (s, 6H), 2.67 (s, 2H), 3.14 (s, 2H), 4.42 (s, 2H), 5.93 (s, 2H), 6.77-6.89 (m, 2H), 6.97 (d, J=1.4 Hz, 1H), 7.18-7.27 (m, 1H), 7.55-7.68 (m, 2H), 9.22 (d, J=8.4 Hz, 1H), 11.93 (br, 1H)m.p.: 193-196° C. (dec.)38. 6-(3-Fluoro-4-hydroxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one0.80 g 6-(3-fluoro-4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one (compound 23) is dissolved in 10 ml DCM and cooled in an ice bath. 8 ml of a 1M solution of BBr3 in DCM is added and stirred for 1 h. 25 ml ice water is added and the mixture is extracted with 75 ml ethyl acetate. The organic layer is washed with brine, dried with MgSO4 and concentrated in vacuo. The product is triturated with diethyl ether to yield 0.59 g of the title compound.mp.: 216-218° C.MS (MH+ found)=389.439. 6-(4-Hydroxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one100 mg 6-(4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one (compound 1) is solved in dichloromethane and cooled to -78° C. 2.6 ml boro tribromide is added and the reaction mixture is stirred for 10 min at -78° C. Allowing to warm up to room temperature, the mixture is stirred for additional 12 h. 20 ml water and 20 ml dichloromethane are added and the mixture is worked up extractively. The combined organic layers are evaporated and the residue is purified by flash chromatography to give 98 mg of the title compound.1H-NMR (400 MHz, d6-DMSO): δ=1.10 (s, 6H), 2.67 (s, 2H), 3.20 (s, 2H), 4.49 (s, 2H), 6.66 (d, J=8.4 Hz, 2H), 7.19 (d, J=8.4 Hz, 2H), 7.28 (br, 1H), 7.65-7.72 (m, 2H), 9.23 (d, J=8.4 Hz, 2H), 12.2 (br, 1H)mp.: decomposes at 210° C.40. 6-(4-Amino-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one0.87 g 3,3-Dimethyl-6-(4-nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one (compound 16) and 2.2 g SnCl2.2H2O are suspended in 20 ml ethanol and heated at 80° C. for 2 h. The mixture is concentrated in vacuo and the residue is stirred with 50 ml DCM and 50 ml 1M NaOH. The organic layer is separated, dried with MgSO4 and concentrated in vacuo. The product is crystallized from ethyl acetate/diethyl ether to yield 0.59 g of the title compound.1H-NMR (200 MHz, CDCl3): δ=1.09 (s, 6H), 2.61 (s, 2H), 3.14 (s, 2H), 3.66 (bs, 2H), 4.37 (bs, 2H), 6.48-6.52 (m, 2H), 6.98-7.02 (m, 2H), 7.12-7.20 (m, 1H), 7.33-7.47 (m, 2H), 9.25 (d, J=8.3 Hz, 1H), 9.59 (bs, 1H)mp.: 123-124° C.The following compounds are obtained by using the procedure of Example 40 analogously:41. 6-(3-Amino-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compound: 3,3-Dimethyl-6-(3-nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one (compound 13)mp.: 232-234° C.MS (MH+ found)=370.342. 6-(4-Amino-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compound: 6-(4-Nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one (compound26)mp.: decomposes at 210° C.MS (MH+ found)=342.343. 6-(3-Amino-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-oneStarting compound: 6-(3-Nitro-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one (compound19)mp.: decomposes at 250° C.MS (MH+ found)=342.344. N-[4-(3,3-Dimethyl-1-oxo-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl]-acetamide0.4 g 6-(4-amino-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one (compound 40) is dissolved in 20 ml DCM and 0.3 ml triethylamine is added followed by 0.10 ml acetyl chloride. The mixture is stirred at RT for 1 h, washed with 1M NaCO3 solution, dried with MgSO4 and concentrated in vacuo. The product is crystallized from ethyl acetate/petroleum ether to yield 0.18 g of the title compound.mp.: 153-154° C.The following compounds are obtained by using the procedure of Example 44 analogously:45. N-[4-(3,3-Dimethyl-1-oxo-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl]-propionamideStarting compounds: 6-(4-Amino-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one (compound 40) and propionyl chloridemp.: decomposes at 235° C.MS (MH+ found)=426.446. N-[4-(1-Oxo-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-6-ylmethyl)-phenyl]-acetamideStarting compounds: 6-(4-Amino-benzyl)-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one (compound 42) and acetyl chloridemp.: decomposes at 230-232° C.MS (MH+ found)=384.347. 6-(4-Methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-1H-indolo[2,3-c]quinolin-1-ol200 mg 6-(4-methoxy-benzyl)-3,3-dimethyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinolin-1-one (comp