Novel Cylopenta[B]Benzofuran Derivatives and the Utilization Thereof

• US 20090018113A1
• Filed: 05/14/2005
• Published: 01/15/2009
• Est. Priority Date: 05/18/2004
• Status: Active Grant

• Current Assignee: Intermed Discovery GmbH
• Original Assignee: Bayer Healthcare AG (Bayer AG)
• Inventors: Gerlach, Irene, Ragot, Jaques, Horvath, Ervin, Thede, Kai, Schuhmacher, Joachim, Fahrig, Thomas, Diedrichs, Nicole
• Granted Patent: US 8,030,347 B2
• Time in Patent Office: Days
• US Class Current: 514/210.190
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 307/93 : condensed with a ring other than six-membered

Abstract

The present application relates to a novel cyclopenta[b]benzofuran derivatives, processes for their preparation and their use for the manufacture of medicaments, in particular for the prophylaxis and/or therapy of acute or chronic disorders characterized by elevated cellular stress, by local or systemic inflammatory processes or by hyperproliferation.

Claims

1. A compound of the formula (I)

2. A compound of the formula (I) as claimed in claim 1, in which

R¹ is hydrogen, benzyloxy, ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)—

NH—

, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino, (C₃-C₆)-cycloalkylamino, N—

(C₃-C₆)-cycloalkyl-N—

(C₁-C₄)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₄)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

and in which

R⁸ is 5- or 6-membered heteroaryl which may be substituted by (C₁-C₄)-alkyl or halogen,

R² is hydrogen, ethoxy or n-propoxy, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino, (C₃-C₆)-cycloalkylamino, N—

(C₃-C₆)-cycloalkyl-N—

(C₁-C₄)-alkylamino or by a 4- to 6-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₄)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

but where R¹ and R² are not simultaneously hydrogen,

R³ is hydroxy or amino

and

R⁴ is hydrogen,

or

R³ and R⁴ together with the carbon atom to which they are bonded form a group of the formula >

C═

O or >

C═

N—

OH,

R⁵ is mono- or di-(C₁-C₄)-alkylaminocarbonyl,

n is the number 0, 1, 2 or 3,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy, (C₆-C₁₀)-aryl, 5- to 6-membered heteroaryl or a group of the formula —

NR⁹R¹⁰,

where aryl and heteroaryl in turn may each be substituted once to twice, identically or differently, by halogen, cyano, (C₁-C₄)-alkylsulfonyl or a group of the formula

and in which

R⁹ and R¹⁰ are independently of one another hydrogen, (C₁-C₄)-alkyl, phenyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a 4- to 7-membered heterocycle,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in the ortho position relative to R⁶, and is hydrogen, halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy or a group of the formula —

NR¹¹R¹², in which

R¹¹ and R¹² are independently of one another hydrogen, (C₁-C₄)-alkyl, phenyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a 4- to 7-membered heterocycle,

or

R⁶ and R⁷ together with the phenyl ring to which they are bonded form a group of the formula

3. A compound of the formula (I) as claimed in claims 1 and 2, in which

R¹ and R² are independently of one another hydrogen, ethoxy or n-propoxy, where ethoxy is substituted in position 2, and n-propoxy in position 3, by methoxy, ethoxy, amino, methylamino, ethylamino, isopropylamino, dimethylamino, diethylamino, cyclopropylamino, N-cyclopropyl-N-methylamino, azetidino or pyrrolidino,

but where R¹ and R² are not simultaneously hydrogen,

R³ is hydroxy or amino,

R⁴ is hydrogen,

R⁵ is methylaminocarbonyl or dimethylaminocarbonyl,

n is the number 0 or 1,

R⁶ is located in the para position relative to the point of linkage of the phenyl ring to the tricycle, and is fluorine, chlorine, bromine, methyl, ethyl, methoxy or ethoxy,

and

R⁷ is hydrogen,

and the salts, solvates and solvates of the salts thereof.

16. A process for preparing a compound of the formula (VI)

17. A compound as defined in any of claims 1 to 15 for the treatment and/or prophylaxis of diseases.

18. The use of a compound as defined in any of claims 1 to 15 for the prophylaxis and/or treatment of inflammatory and autoimmune diseases, neurodegenerative disorders and hyperproliferative disorders.

19. A medicament comprising a compound as defined in any of claims 1 to 15 in combination with an inert, non-toxic, pharmaceutically suitable excipient.

20. The medicament as claimed in claim 19 for the prophylaxis and/or treatment of inflammatory and autoimmune diseases, neurodegenerative disorders and hyperproliferative disorders.

21. A method for the prophylaxis and/or treatment of inflammatory and autoimmune diseases, neurodegenerative disorders and hyperproliferative disorders in humans and animals by administration of an effective amount of at least one compound as defined in any of claims 1 to 15, or of a medicament as defined in either of claims 19 and 20.

4. A compound of the formula (I) in which

R¹ is hydrogen, benzyloxy, ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)—

NH—

, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₆)-alkoxy, amino, mono- or di-(C₁-C₆)-alkylamino, (C₃-C₈)-cycloalkylamino, N—

(C₃-C₈)-cycloalkyl-N4C₁-C₆)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₄)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

and in which

R⁸ is 5- or 6-membered heteroaryl which may be substituted by (C₁-C₄)-alkyl or halogen,

R² is hydrogen, ethoxy or n-propoxy, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₆)-alkoxy, amino, mono- or di-(C₁-C₆)-alkylamino, (C₃-C8)-cycloalkylamino, N—

(C₃-C8)-cycloalkyl-N—

(C₁-C₆)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₆)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

but where R¹ and R² are not simultaneously hydrogen,

R³ is hydroxy or amino

and

R⁴ is hydrogen,

or

R³ and R⁴ together with the carbon atom to which they are bonded form a group of the formula >

C═

O or >

C═

N—

OH,

R⁵ is hydrogen,

n is the number 0, 1, 2 or 3,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is (C₆-C₁₀)-aryl, 5- to 10-membered heteroaryl or a group of the formula —

NR⁹R¹⁰,

where aryl and heteroaryl in turn may each be substituted once to twice, identically or differently, by halogen, cyano, (C₁-C₄)-alkylsulfonyl or a group of the formula —

NR⁹R¹⁰,

and in which

R⁹ and R¹⁰ are independently of one another hydrogen, (C₁-C₆)-alkyl, phenyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a 4- to 7-membered heterocycle,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in the ortho position relative to R⁶, and is hydrogen, halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy or a group of the formula —

NR¹¹R¹², in which

R¹¹ and R¹² are independently of one another hydrogen, (C₁-C₆)-alkyl, phenyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a 4- to 7-membered heterocycle,

or

R⁶ and R⁷ together with the phenyl ring to which they are bonded form a group of the formula

5. A compound of the formula (I) as claimed in claim 4, in which

R¹ is hydrogen, benzyloxy, ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)—

NH—

, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)alkylamino, (C₃-C₆)-cycloalkylamino, N—

(C₃-C₆)-cycloalkyl-N—

(C₁-C₄)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₄)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

and in which

R⁸ is 5- or 6-membered heteroaryl which may be substituted by (C₁-C₄)-alkyl or halogen,

R² is hydrogen, ethoxy or n-propoxy, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino, (C₃-C₆)-cycloalkylamino, N—

(C₃-C₆)-cycloalkyl-N—

(C₁-C₄)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₄)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

but where R¹ and R² are not simultaneously hydrogen,

R³ is hydroxy or amino

and

R⁴ is hydrogen,

or

R³ and R⁴ together with the carbon atom to which they are bonded form a group of the formula >

C═

O or >

C═

N—

OH,

R⁵ is hydrogen,

n is the number 0, 1, 2 or 3,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is (C₆-C₁₀)-aryl, 5- to 6-membered heteroaryl or a group of the formula —

NR⁹R¹⁰,

where aryl and heteroaryl in turn may each be substituted once to twice, identically or differently, by halogen, cyano, (C₁-C₄)-alkylsulfonyl or a group of the formula —

NR⁹R¹⁰,

and in which

R⁹ and R¹⁰ are independently of one another hydrogen, (C₁-C₄)-alkyl, phenyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a 4- to 7-membered heterocycle,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in the ortho position relative to R⁶, and is hydrogen, halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy or a group of the formula —

NR¹¹R¹² in which

R¹¹ and R¹² are independently of one another hydrogen, (C₁-C₄)-alkyl, phenyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a 4- to 7-membered heterocycle,

or

R⁶ and R⁷, together with the phenyl ring to which they are bonded form a group of the formula

6. A compound of the formula (1) as claimed in claims 4 and 5, in which

R¹ is hydrogen, ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)NH—

, where ethoxy may be substituted in position 2, and n-propoxy in position 3, by methoxy, ethoxy, amino, methylamino, ethylamino, isopropylamino, dimethylamino, diethylamino, cyclopropylamino, N-cyclopropyl-N-methylamino, azetidino or pyrrolidino, in which

R⁸ is pridyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl or thiadiazolyl, each of which may be substituted by methyl, ethyl, fluorine or chlorine,

R² is hydrogen, ethoxy or n-propoxy, where ethoxy may be substituted in position 2, and n-propoxy in position 3, by methoxy, ethoxy, amino, methylamino, ethylamino, isopropylamino, dimethylamino, diethylamino, cyclopropylamino, N-cyclopropyl-N-methylamino, azetidino or pyrrolidino,

but where R¹ and R² are not simultaneously hydrogen,

R³ is hydroxy or amino,

R⁴ is hydrogen,

R⁵ is hydrogen,

n is the number 0 or 1,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is phenyl, thienyl, indolyl, quinoxalinyl or a group of the formula —

NR⁹R¹⁰,

where phenyl, thienyl and indolyl in turn may each be substituted once to twice, identically or differently, by fluorine, chlorine, bromine, cyano or amino, and in which

R⁹ and R¹⁰ are independently of one another hydrogen, methyl, ethyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a pyrrolidino ring,

and

R⁷ is hydrogen,

and the salts, solvates and solvates of the salts thereof.

7. A compound of the formula (I) in which

R¹ is hydrogen, benzyloxy, ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)—

NH—

, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₆)-alkoxy, amino, mono- or di-(C₁-C₆)-alkylamino, (C₃-C₈)-cycloalkylamino, N—

(C₃-C₈)-cycloalkyl-N—

(C₁-C₆)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₆)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

and in which

R⁸ is 5- or 6-membered heteroaryl which may be substituted by (C₁-C₄)-alkyl or halogen,

R² is hydrogen, ethoxy or n-propoxy, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₆)-alkoxy, amino, mono- or di-(C₁-C₆)-alkylamino, (C₃-C₈)-cycloalkylamino, N—

(C₃-C₈)-cycloalkyl-N—

(C₁-C₆)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₆)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

but where R¹ and R² are not simultaneously hydrogen,

R³ is amino

and

R⁴ is hydrogen,

or

R³ and R⁴ together with the carbon atom to which they are bonded form a group of the formula >

C═

N—

OH,

R⁵ is hydrogen,

n is the number 0, 1, 2 or 3,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is halogen, (C₁-C₆)alkyl or (C₁-C₆)alkoxy,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in ortho position relative to R⁶, and is hydrogen, halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy or a group of the formula —

NR¹¹R¹² in which

R¹¹ and R¹² are independently of one another hydrogen, (C₁-C₆)-alkyl, phenyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a 4 to 7-membered heterocycle,

or

R⁶ and R⁷ together with the phenyl ring to which they are bonded form a group of the formula

8. A compound of the formula (I) as claimed in claim 7, in which

R¹ is hydrogen, benzyloxy, ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)—

NH—

, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₄)alkoxy, amino, mono- or di-(C₁-C₄)alkylamino, (C₃-C₆)cycloalkylamino, N—

(C₃-C₆)cycloalkyl-N—

(C₁-C₄)alkylamino or by a 4 to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₄)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)alkylamino,

and in which

R⁸ is 5- or 6membered heteroaryl which may be substituted by (C₁-C₄)-alkyl or halogen,

R² is hydrogen, ethoxy or n-propoxy, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino, (C₃-C₆)-cycloalkylamino, N—

(C₃-C₆)-cycloalkyl-N—

(C₁-C₄)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₄)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

but where R¹ and R² are not simultaneously hydrogen,

R³ is amino

and

R⁴ is hydrogen

or

R³ and R⁴ together with the carbon atom to which they are bonded form a group of the formula >

C═

N—

OH,

R⁵ is hydrogen,

n is the number 0, 1, 2 or 3,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is halogen, (C₁-C₄)-alkyl or (C₁-C₄)-alkoxy,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in the ortho position relative to R⁶, and is hydrogen, halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy or a group of the formula —

NR¹¹R¹², in which

R¹¹ and R¹² are independently of one another hydrogen, (C₁-C₆)-alkyl, phenyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a 4- to 7-membered heterocycle,

or

R⁶ and R⁷ together with the phenyl ring to which they are bonded form a group of the formula

9. A compound of the formula (I) as claimed in claims 7 and 8, in which

R¹ is hydrogen, ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)—

NH—

, where ethoxy may be substituted in position 2, and n-propoxy in position 3, by methoxy, ethoxy, amino, methylamino, ethylamino, isopropylamino, dimethylamino, diethylamino, cyclopropylamino, N-cyclopropyl-N-methylamino, azetidino or pyrrolidino, in which

R⁸ is pyridyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl or thiadiazolyl, each of which may be substituted by methyl, ethyl, fluorine or chlorine,

R² is hydrogen, ethoxy or n-propoxy, where ethoxy may be substituted in position 2, and n-propoxy in position 3, by methoxy, ethoxy, amino, methylamino, ethylamino, isopropylamino, dimethylamino, diethylamino, cyclopropylamino, N-cyclopropyl-N-methylamino, azetidino or pyrrolidino,

but where R¹ and R² are not simultaneously hydrogen,

R³ is amino,

R⁴ is hydrogen

R⁵ is hydrogen,

n is the number 0 or 1,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is fluorine, chlorine, bromine, methyl, ethyl, methoxy or ethoxy,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in the ortho position relative to R⁶, and is hydrogen, fluorine, chlorine, bromine, methyl, ethyl, methoxy, ethoxy or a group of the formula —

NR¹¹R¹² in which

R¹¹ and R¹² are independently of one another hydrogen, methyl, ethyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a pyrrolidino or piperidino ring,

or

R⁶ and R⁷ together with the phenyl ring to which they are bonded form a group of the formula

10. A compound of the formula (I) in which

R¹ is hydrogen, benzyloxy, ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)—

NH—

, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₆)-alkoxy, amino, mono- or di-(C₁-C₆)-alkylamino, (C₃-C₈)-cycloalkylamino, N—

(C₃-C8)-cycloalkyl-N—

(C₁-C₆)-alkylamino or by a 4 to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₆)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

and in which

R⁸ is 5- or 6-membered heteroaryl which may be substituted by (C₁-C₄)-alkyl or halogen,

R² is hydrogen, ethoxy or n-propoxy, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₆)-alkoxy, amino, mono- or di-(C₁-C₆)-alkylamino, (C₃-C₈)-cycloalkylamino, N—

(C₃-C₈)-cycloalkyl-N—

(C₁-C₆)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₆)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

but where R¹ and R² are not simultaneously hydrogen,

R³ is hydroxy

and

R⁴ is hydrogen,

or

R³ and R⁴ together with the carbon atom to which they are bonded form a group of the formula >

C═

O,

R⁵ is hydrogen,

n is the number 0, 1, 2 or 3,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is halogen, (C₁-C₆)-alkyl or (C₁-C₆)-alkoxy,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in the ortho position relative to R⁶, and is hydrogen, halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy or a group of the formula —

NR¹¹R¹², in which

R¹¹ and R¹² are independently of one another hydrogen, (C₁-C₆)-alkyl, phenyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a 4- to 7-membered heterocycle,

or

R⁶ and R⁷ together with the phenyl ring to which they are bonded form a group of the formula

11. A compound of the formula (I) as claimed in claim 10, in which

R¹ is hydrogen, benzyloxy, ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)—

NH—

, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino, (C₃-C₆)-cycloalkylamino, N—

(C₃-C₆)-cycloalkyl-N—

(C₁-C₄)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₄)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

and in which

R⁸ is 5- or 6-membered heteroaryl which may be substituted by (C₁-C₄)-alkyl or halogen,

R² is hydrogen, ethoxy or n-propoxy, where ethoxy may be substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino, (C₃-C₆)cycloalkylamino, N—

(C₃-C₆)-cycloalkyl-N—

(C₁-C₄)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₄)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

but where R¹ and R² are not simultaneously hydrogen,

R³ is hydroxy

and

R⁴ is hydrogen,

or

R³ and R⁴ together with the carbon atom to which they are bonded form a group of the formula >

C═

O,

R⁵ is hydrogen,

n is the number 0, 1, 2 or 3,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is halogen, (C₁-C₄)-alkyl or (C₁-C₄)-alkoxy,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in the ortho position relative to R⁶, and is hydrogen, halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy or a group of the formula —

NR¹¹R¹² in which

R¹¹ and R¹² are independently of one another hydrogen, (C₁-C₄)-alkyl, phenyl, benzyl or pyridylmethyl or together with the nitrogen atom to which they are bonded form a 4- to 7-membered heterocycle,

or

R⁶ and R⁷ together with the phenyl ring to which they are bonded form a group of the formula

12. A compound of the formula (I) as claimed in claims 10 and 11, in which

R¹ is hydrogen, ethoxy, n-propoxy or a grouop of the formula R⁸—

C(═

O)—

NH—

, where ethoxy may be substituted in position 2, and n-propoxy in position 3, by methoxy, ethoxy, amino, methylamino, ethylamino, isopropylamino, dimethylamino, diethylamino, cyclopropylamino, N-cyclopropyl-N-methylamino, azetidino or pyrrolidino, in which

R⁸ is pyridyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl or thiadiazolyl, each of which may be substituted by methyl, ethyl, fluorine or chlorine,

R² is hydrogen, ethoxy or n-propoxy, where ethoxy may be substituted in position 2, and n-propoxy in position 3, by methoxy, ethoxy, amino, methylamino, ethylamino, isopropylamino, dimethylamino, diethylamino, cyclopropylamino, N-cyclopropyl-N-methylamino, azetidino or pyrrolidino,

where R¹ or R² is hydrogen, but both are not simultaneously hydrogen,

R³ is hydroxy

and

R⁴ is hydrogen,

or

R³ and R⁴ together with the carbon atom to which they are bonded form a group of the formula >

C═

O,

R⁵ is hydrogen,

n is the number 0 or 1,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is fluorine, chlorine, bromine, methyl, ethyl, methoxy or ethoxy,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in the ortho position relative to R⁶, and is hydrogen, fluorine, chlorine, bromine, methyl, ethyl, methoxy, ethoxy or a group of the formula —

NR¹¹R¹² in which

R¹¹ and R¹² are independently of one another hydrogen, methyl, ethyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a pyrrolidino or piperidino ring,

or

R⁶ and R⁷ together with the phenyl ring to which they are bonded form a group of the formula

13. A compound of the formula (I) in which

R¹ is ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)—

NH—

, where ethoxy is substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₆)-alkoxy, amino, mono- or di-(C₁-C₆)-alkylamino, (C₃-C₈)-cycloalkylamino, N—

(C₃-C₈)-cycloalkyl-N—

(C₁-C₆)-alkylamino or by a 4 to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₆)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

and in which

R⁸ is 5- or 6-membered heteroaryl which may be substituted by (C₁-C₄)-alkyl or halogen,

R² is ethoxy or n-propoxy, where ethoxy is substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₆)-alkoxy, amino, mono- or di-(C₁-C₆)-alkylamino, (C₃-C₈)-cycloalkylamino, N—

(C₃-C₈)-cycloalkyl-N—

(C₁-C₆)-alkylamino or by a 4 to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₆)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

R³ is hydroxy

and

R⁴ is hydrogen,

or

R³ and R⁴ together with the carbon atom to which they are bonded form a group of the formula >

C═

O,

R⁵ is hydrogen,

n is the number 0, 1, 2 or 3,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is halogen, (C₁-C₆)-alkyl or (C₁-C₆)-alkoxy,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in the ortho position relative to R⁶, and is hydrogen, halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy or a group of the formula —

NR¹¹R¹², in which

R¹¹ and R¹² are independently of one another hydrogen, (C₁-C₆)-alkyl, phenyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a 4- to 7-membered heterocycle,

or

R⁶ and R⁷ together with the phenyl ring to which they are bonded form a group of the formula

14. A compound of the formula (I) as claimed in claim 13, in which

R¹ is ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)—

NH—

, where ethoxy is substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino, (C₃-C₆)-cycloalkylamino, N—

(C₃-C₆)-cycloalkyl-N—

(C₁-C₄)-alkylamino or by a 4 to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₄)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

and in which

R⁸ is a 5- or 6-membered heteroaryl which may be substituted by (C₁-C₄)-alkyl or halogen,

R² is ethoxy or n-propoxy, where ethoxy is substituted in position 2, and n-propoxy in position 2 or 3, by (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino, (C₃-C₆)-cycloalkylamino, N—

(C₃-C₆)-cycloalkyl-N—

(C₁-C₄)-alkylamino or by a 4- to 7-membered heterocycle which is bonded via an N atom,

where mono- and di-(C₁-C₄)-alkylamino in turn may be substituted by hydroxy, (C₁-C₄)-alkoxy, amino, mono- or di-(C₁-C₄)-alkylamino,

R³ is hydroxy

and

R⁴ is hydrogen,

or

R³ and R⁴ together with the carbon atom to which they are bonded form a group of the formula >

C═

O,

R⁵ is hydrogen,

n is the number 0, 1, 2 or 3,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is halogen, (C₁-C₄)-alkyl or (C₁-C₄)-alkoxy,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in the ortho position relative to R⁶, and is hydrogen, halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy or a group of the formula —

NR¹¹R¹² in which

R¹¹ and R¹² are independently of one another hydrogen, (C₁-C₄)-alkyl, phenyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a 4 to 7-membered heterocycle,

or

R⁶ and R⁷ together with the phenyl ring to which they are bonded form a group of the formula

15. A compound of the formula (I) as claimed in claims 13 and 14, in which

R¹ is ethoxy, n-propoxy or a group of the formula R⁸—

C(═

O)—

NH—

, where ethoxy is substituted in position 2, and n-propoxy in position 3, by methoxy, ethoxy, amino, methylamino, ethylamino, isopropylamino, dimethylamino, diethylamino, cyclopropylamino, N-cyclopropyl-N-methylamino, azetidino or pyrrolidino, in which

R⁸ is pyridyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl or thiadiazolyl, each of which may be substituted by methyl, ethyl, fluorine or chlorine,

R² is ethoxy or n-propoxy, where ethoxy is substituted in position 2, and n-propoxy in position 3, by methoxy, ethoxy, amino, methylamino, ethylamino, isopropylamino, dimethylamino, diethylamino, cyclopropylamino, N-cyclopropyl-N-methylamino, azetidino or pyrrolidino,

R³ is hydroxy

and

R⁴ is hydrogen,

or

R³ and R⁴ together with the carbon atom to which they are bonded form a group of the formula >

C═

O,

R⁵ is hydrogen,

n is the number 0 or 1,

R⁶ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and is fluorine, chlorine, bromine, methyl, ethyl, methoxy or ethoxy,

and

R⁷ is located in the meta or para position relative to the point of linkage of the phenyl ring to the tricycle, and in the ortho position relative to R⁶, and is hydrogen, fluorine, chlorine, bromine, methyl, ethyl, methoxy, ethoxy or a group of the formula —

NR¹¹R¹² in which

R¹¹ and R¹² are independently of one another hydrogen, methyl, ethyl, benzyl or pyridylmethyl, or together with the nitrogen atom to which they are bonded form a pyrrolidino or piperidino ring,

or

R⁶ and R⁷ together with the phenyl ring to which they are bonded form a group of the formula