IP Library › Granted Patent US 8,609,698

Granted Patent B2

US 8,609,698 · App. 12/447,207 · Granted Dec 17, 2013

Substituted dipyridyl-dihydropyrazolones and use thereof

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Quick Facts

Patent No.: US 8,609,698
App. No.: 12/447,207
Granted: Dec 17, 2013
Kind: B2

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Abstract

The present application relates to novel substituted dipyridyldihydropyrazolone derivatives, processes for their preparation, their use for treatment and/or prophylaxis of diseases and their use for the preparation of medicaments for treatment and/or prophylaxis of diseases, in particular cardiovascular and hematological diseases and kidney diseases, and for promoting wound healing.

Claims (237)

1. A compound of the formula (I)

A represents CH,

R 1 and R 2 are identical or different and for each individual occurrence represent a substituent independently of one another selected from the group consisting of halogen, cyano, nitro, hydroxyl, amino, hydroxycarbonyl, aminocarbonyl, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, (C 3 -C 7 )-cycloalkyl, phenyl, —C(═O)—R 4 , —C(═O)—OR 5 , —C(═O)—NR 6 R 7 , —O—C(═O)—R 8 , —O—C(═O)—NR 9 R 10 , —NR 11 —C(═O)—R 12 , —NR 13 —C(═O)—OR 14 , —NR 15 —C(═O)—NR 16 R 17 , —NR 18 —SO 2 —R 19 , —SO 2 —R 20 , —SO 2 —NR 21 R 22 , —OR 23 , —SR 24 and —NR 25 R 26 in which

(i) (C 1 -C 6 )-alkyl and (C 1 -C 6 )-alkoxy for their part may in each case be mono- to trisubstituted by identical or different radicals selected from the group consisting of halogen, cyano, oxo, hydroxyl, amino, hydroxycarbonyl, aminocarbonyl, (C 3 -C 7 )-cycloalkyl, phenyl, —C(═O)—R 4 , —C(═O)—OR 5 , —C(═O)—NR 6 R 7 , —O—C(═O)—R 8 , —O—C(═O)—NR 9 R 10 , NR 11 —C(—O)—R 12 , —NR 13 (═O)—OR 14 , —NR 15 —C(═O)—NR 16 R 17 , NR 18 —SO 2 —R 19 , —SO 2 —R 20 , —SO 2 —NR 21 R 22 , —OR 23 , —SR 24 and —NR 25 R 26 ,

where the last-mentioned cycloalkyl, and phenyl radicals for their part may in each case be substituted up to three times by identical or different substituents selected from the group consisting of halogen, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )-alkoxy, trifluoromethoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl and (C 1 -C 4 )-alkoxycarbonyl,

(ii) (C 3 -C 7 )-cycloalkyl, and phenyl for their part may in each case be mono- to trisubstituted by identical or different radicals selected from the group consisting of (C 1 -C 6 )-alkyl, halogen, cyano, oxo, hydroxyl, amino, hydroxycarbonyl, aminocarbonyl, —C(═O)—R 4 , —C(═O)—OR 5 , —C(═O)—NR 6 R 7 , —O—C(═O)—R 8 , —O—C(═O)—NR 9 R 10 , —NR 11 —C(═O)—R 12 , —NR 13 —C(═O)—OR 14 , —NR 15 —C(═O)—NR 16 R 17 , —NR 18 —SO 2 —R 19 , —SO 2 —R 20 , —SO 2 —NR 21 R 22 , —OR 23 , —SR 24 and —NR 25 R 26 ,

where the last-mentioned alkyl radical for its part may be substituted up to three times by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, (C 1 -C 4 )-alkoxycarbonyl, (C 3 -C 7 )-cycloalkyl, and phenyl,

(iii) R 4 , R 5 , R 6 , R 8 , R 9 , R 12 , R 14 , R 16 , R 19 , R 20 , R 21 , R 23 , R 24 and R 25 independently of one another for each individual occurrence represent a radical selected from the group consisting of (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl, and phenyl, where

(C 3 -C 7 )-cycloalkyl, and phenyl for their part may in each case be substituted up to three times by identical or different substituents selected from the group consisting of halogen, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )-alkoxy, trifluoromethoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl and (C 1 -C 4 )-alkoxycarbonyl

and

(C 1 -C 6 )-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, (C 1 -C 4 )-alkoxycarbonyl, (C 3 -C 7 )-cycloalkyl, and phenyl, and

(iv) R 7 , R 10 , R 11 , R 13 , R 15 , R 17 , R 18 , R 22 and R 26 independently of one another for each individual occurrence represent a radical selected from the group consisting of hydrogen and (C 1 -C 6 )-alkyl, where (C 1 -C 6 )-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl and (C 1 -C 4 )-alkoxycarbonyl,

m and n independently of one another represent the number 0, 1, 2 or 3,

where if R 1 or R 2 are present more than once, their meanings may in each case be identical or different,

and

R 3 represents hydrogen, (C 1 -C 6 )-alkyl or (C 3 -C 7 )-cycloalkyl,

or a salt thereof.

2. The compound of claim 1 in which

A represents CH,

R 1 represents a substituent selected from the group consisting of (C 3 -C 6 )-cycloalkyl, phenyl, —OC(═O)—NR 9 R 10 , —NR 11 —C(═O)—R 12 , —NR 13 —C(═O)—OR 14 , —NR 15 —C(═O)—NR 16 R 17 , —NR 18 —SO 2 —R 19 and —NR 25 R 26 in which

(i) (C 3 -C 6 )-cycloalkyl, and phenyl for their part may in each case be mono- to trisubstituted by identical or different radicals selected from the group consisting of (C 1 -C 6 )-alkyl, halogen, cyano, oxo, hydroxyl, amino, hydroxycarbonyl, aminocarbonyl, —C(═O)—NR 6 R 7 , —O—C(═O)—NR 9 R 10 , —NR 11 —C(═O)—R 12 , —NR 13 —C(═O)—OR 14 , —NR 15 —C(═O)—NR 16 R 17 , —NR 18 —SO 2 —R 19 , —OR 23 and —NR 25 R 26 ,

(ii) R 6 , R 9 , R 12 , R 14 , R 16 , R 19 , R 23 and R 25 independently of one another for each individual occurrence represent a radical selected from the group consisting of (C 1 -C 6 )-alkyl and (C 3 -C 6 )-cycloalkyl, where

(C 3 -C 6 )-cycloalkyl may be substituted up to three times by identical or different substituents selected from the group consisting of halogen, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )-alkoxy, trifluoromethoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl and (C 1 -C 4 )-alkoxycarbonyl and

(iii) R 7 , R 10 , R 11 , R 13 , R 15 , R 17 , R 18 and R 26 independently of one another for each individual occurrence represent a radical selected from the group consisting of hydrogen and (C 1 -C 6 )-alkyl,

where (C 1 -C 6 )-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl and (C 1 -C 4 )-alkoxycarbonyl,

R 2 represents a substituent selected from the group consisting of —O—C(═O)—NR 9A R 10A , —NR 11A —C(═O)—R 12A , —NR 13A —C(═O)—OR 14A , —NR 15A —C(═O)—NR 16A R 17A , NR 18A —SO 2 —R 19A and —NR 25A R 26A in which

(i) R 9A , R 12A , R 14A , R 16A , R 19A and R 25A independently of one another represent (C 1 -C 6 )-alkyl represent (C 1 -C 6 )-alkyl which may in each case be substituted by halogen, cyano, trifluoromethyl, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl or (C 1 -C 4 )-alkoxycarbonyl,

(ii) R 10A , R 11A , R 13A , R 15A , R 17A , R 18A and R 26A independently of one another represent hydrogen or (C 1 -C 6 )-alkyl which may in each case be substituted by halogen, cyano, trifluoromethyl, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl or (C 1 -C 4 )-alkoxycarbonyl,

m represents the number 1,

n represents the number 0 or 1

and

R 3 represents hydrogen,

or a salt thereof.

3. The compound of claim 1 in which

A represents CH,

R 1 represents a substituent selected from the group consisting of (C 3 -C 6 )-cycloalkyl, phenyl, —O—C(═O)—NR 9 R 10 , —NR 11 —C(═O)—R 12 , —NR 13 —C(═O)—OR 14 , —NR 15 —C(═O)—NR 16 R 17 , —NR 18 —SO 2 —R 19 and —NR 25 R 26 in which

(ii) R 6 , R 9 , R 12 , R 14 , R 16 , R 19 , R 23 and R 25 independently of one another for each individual occurrence represent a radical selected from the group consisting of (C 1 -C 6 )-alkyl, and (C 3 -C 6 )-cycloalkyl, where

R 2 represents a substituent selected from the group consisting of halogen, cyano, nitro, (C 1 -C 6 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 6 )-alkoxy, trifluoromethoxy, amino, hydroxycarbonyl and —C(═O)—NH—R 7A in which (C 1 -C 6 )-alkyl and (C 1 -C 6 )-alkoxy for their part may be substituted by hydroxyl

and

R 7A represents hydrogen or (C 1 -C 4 )-alkyl,

m represents the number 1,

n represents the number 0 or 1

and

R 3 represents hydrogen,

or a salt thereof.

4. The compound of claim 1 in which

A represents CH,

R 1 represents a substituent selected from the group consisting of (C 1 -C 6 )-alkyl, trifluoromethyl, halogen, cyano, nitro, hydroxyl, (C 1 -C 6 )-alkoxy, amino, hydroxycarbonyl, (C 1 -C 6 )-alkoxycarbonyl and —C(═O)—NH—R 7 in which

(C 1 -C 6 )-alkyl for its part may be substituted by hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino or a group of the formula —NH—C(═O)—R 12 , —NH—C(═O)—NH—R 16 or —NH—SO 2 —R 19 in which

R 12 , R 16 and R 19 each represent (C 1 -C 6 )-alkyl which may be substituted by hydroxyl or (C 1 -C 4 )-alkoxy,

and

R 7 represents hydrogen or (C 1 -C 6 )-alkyl which may be substituted by hydroxyl or (C 1 -C 4 )-alkoxy,

(i) R 9A , R 12A , R 14A , R 16A , R 19A and R 25A independently of one another represent (C 1 -C 6 )-alkyl which may in each case be substituted by halogen, cyano, trifluoromethyl, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl or (C 1 -C 4 )-alkoxycarbonyl, and

m represents the number 1,

n represents the number 0 or 1

and

R 3 represents hydrogen,

or a salt thereof.

5. The compound of claim 1 in which

A represents CH,

R 1 represents (C 1 -C 6 )-alkyl which

(i) is mono- or disubstituted by identical or different radicals from the group consisting of halogen, cyano, trifluoromethyl, (C 3 -C 6 )-cyclo-alkyl, hydroxycarbonyl, aminocarbonyl, —C(═O)—NR 6 R 7 , —O—C(═O)—NR 9 R 10 , —NR 11 —C(═O)—R 12 , —NR 13 —C(═O)—OR 14 , —NR 15 —C(═O)—NR 16 R 17 , —NR 18 —SO 2 —R 19 , —OR 23 and —NR 25 R 26

and additionally may be substituted by hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino or (C 1 -C 4 )-acylamino,

(ii) is disubstituted by identical or different radicals from the group consisting of hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino and (C 1 -C 4 )-acylamino in which

(a) the abovementioned cycloalkyl radical may be substituted up to three times by identical or different substituents selected from the group consisting of halogen, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )-alkoxy, trifluoromethoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl and (C 1 -C 4 )-alkoxycarbonyl,

(b) R 7 , R 10 , R 11 , R 13 , R 15 , R 17 , R 18 and R 26 independently of one another for each individual occurrence represent a radical selected from the group consisting of hydrogen and (C 1 -C 6 )-alkyl, where (C 1 -C 6 )-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl and (C 1 -C 4 )-alkoxycarbonyl,

(c) R 6 , R 9 and R 14 independently of one another for each individual occurrence represent a radical selected from the group consisting of (C 1 -C 6 )-alkyl, and (C 3 -C 6 )-cycloalkyl, where

and

(d) R 12 , R 16 and R 19 independently of one another for each individual occurrence represent a radical selected from the group consisting of (C 1 -C 6 )-alkyl, and (C 3 -C 6 )-cycloalkyl, where

and

(C 1 -C 6 )-alkyl is mono- to trisubstituted by identical or different radicals selected from the group consisting of halogen, cyano, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, (C 1 -C 4 )-alkoxycarbonyl, and (C 3 -C 6 )-cyclo-alkyl,

(e) R 23 and R 25 independently of one another for each individual occurrence represent a radical selected from the group consisting of (C 1 -C 6 )-alkyl, and (C 3 -C 6 )-cycloalkyl, where

and

(C 1 -C 6 )-alkyl is mono- to trisubstituted by identical or different radicals selected from the group consisting of halogen, cyano, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, (C 1 -C 4 )-alkoxycarbonyl, and (C 3 -C 6 )-cycloalkyl,

R 2 represents a substituent selected from the group consisting of halogen, cyano, (C 1 -C 6 )-alkyl, trifluoromethyl, hydroxyl, trifluoromethoxy, amino, hydroxycarbonyl, aminocarbonyl, —C(═O)—NR 6A R 7A , —O—C(═O)—NR 9A R 10A , —NR 11A —C(═O)—R 12A , —NR 13A —C(═O)—OR 14A , —NR 15A —C(═O)—NR 16A R 17A , —NR 18A —SO 2 —R 19A —OR 23A and —NR 25A R 26A in which

(i) (C 1 -C 6 )-alkyl may be substituted by halogen, cyano, trifluoromethyl, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl or (C 1 -C 4 )-alkoxycarbonyl,

(ii) R 6A , R 9A , R 12A , R 14A , R 16A , R 19A , R 23A and R 25A independently of one another represent (C 1 -C 6 )-alkyl which may in each case be substituted by halogen, cyano, trifluoromethyl, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkyl amino, di-(C 1 -C 4 )-alkyl amino, hydroxycarbonyl or (C 1 -C 4 )-alkoxycarbonyl,

(III) R 7A , R 10A , R 11A , R 13A , R 15A , R 17A , R 18A and R 26A independently of one another represent hydrogen or (C 1 -C 6 )-alkyl which may in each case be substituted by halogen, cyano, trifluoromethyl, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl or (C 1 -C 4 )-alkoxycarbonyl,

m represents the number 1,

n represents the number 0 or 1

and

R 3 represents hydrogen,

or a salt thereof.

6. The compound of claim 1 in which

A represents CH,

R 1 represents (C 1 -C 6 )-alkoxy which is mono- or disubstituted by identical or different radicals selected from the group consisting of halogen, cyano, trifluoromethyl, (C 3 -C 6 )-cycloalkyl, hydroxyl, amino, hydroxycarbonyl, aminocarbonyl, —C(═O)—NR 6 R 7 , —O—C(═O)—NR 9 R 10 , NR 11 —C(═O)—R 12 , —NR 13 —C(═O)—OR 14 , —NR 15 —C(═O)—NR 16 R 17 , NR 18 —SO 2 —R 19 , —OR 23 and —NR 25 R 26 in which

(i) (C 3 -C 6 )-cycloalkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )-alkoxy, trifluoromethoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl and (C 1 -C 4 )-alkoxycarbonyl,

R 2 represents a substituent selected from the group consisting of halogen, cyano, (C 1 -C 6 )-alkyl, trifluoromethyl, hydroxyl, trifluoromethoxy, amino, hydroxycarbonyl, aminocarbonyl, —C(═O)—NR 6A R 7A , —O—C(═O)—NR 9A R 10A , NR 11A —C(═O)—R 12A , —NR 13A —C(═O)—OR 14A , —NR 15A —C(═O)—NR 16A R 17A , —NR 18A —SO 2 —R 19A , —OR 23A and —NR 25A R 26A in which

(iii) R 7A , R 10A , R 11A , R 13A , R 15A , R 17A , R 18A and R 26A independently of one another represent hydrogen or (C 1 -C 6 )-alkyl which may in each case be substituted by halogen, cyano, trifluoromethyl, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl or (C 1 -C 4 )-alkoxycarbonyl,

m represents the number 1,

n represents the number 0 or 1

and

R 3 represents hydrogen,

or a salt thereof.

7. The compound of claim 1 in which

A represents CH,

R 1 represents the group —C(═O)—NR 6 R 7

in which (i)

R 6 represents (C 3 -C 6 )-cycloalkyl which may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )-alkoxy, trifluoromethoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl and (C 1 -C 4 )-alkoxycarbonyl,

represents (C 1 -C 6 )-alkyl which

(a) is mono- or disubstituted by identical or different radicals selected from the group consisting of halogen, cyano, trifluoromethyl, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, (C 1 -C 4 )-alkoxycarbonyl, and (C 3 -C 6 )-cycloalkyl and may additionally be substituted by hydroxyl or (C 1 -C 4 )-alkoxy,

(b) is disubstituted by hydroxyl and/or (C 1 -C 4 )-alkoxy,

and

R 7 represents hydrogen,

or in which (ii)

R 6 represents (C 1 -C 6 )-alkyl or (C 3 -C 6 )-cycloalkyl, where

and

R 7 represents (C 1 -C 6 )-alkyl which may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl and (C 1 -C 4 )-alkoxycarbonyl,

R 2 represents a substituent selected from the group consisting of halogen, cyano, (C 1 -C 6 )-alkyl, trifluoromethyl, hydroxyl, trifluoromethoxy, amino, hydroxycarbonyl, aminocarbonyl, —C(═O)—NR 6A R 7A , —O—C(═O)—NR 9A R 10A , NR 11A —C(═O)—R 12A , NR 13A —C(═O)—OR 14A , —NR 15A —C(═O)—NR 16A R 17A , —NR 18A —SO 2 —R 19A , —OR 23A and —NR 25A R 26A in which

(ii) R 6A , R 9A , R 12A , R 14A , R 16A , R 19A , R 23A and R 25A independently of one another represent (C 1 -C 6 )-alkyl which may in each case be substituted by halogen, cyano, trifluoromethyl, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl or (C 1 -C 4 )-alkoxycarbonyl,

m represents the number 1,

n represents the number 0 or 1

and

R 3 represents hydrogen,

and salts thereof.

8. The compound as claimed in claim 1 of the formula (I-A) or (I-B)

in which

R 1 represents phenyl which may be mono- or disubstituted by identical or different radicals selected from the group consisting of fluorine, chlorine, bromine, cyano, (C 1 -C 4 )-alkyl, hydroxyl, amino, hydroxycarbonyl, —OR 23 and —NR 25 R 26 in which

(C 1 -C 4 )-alkyl for its part may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, cyano, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, (C 3 -C 6 )-cycloalkyl, and phenyl,

R 23 and R 25 independently of one another for each individual occurrence represent (C 1 -C 4 )-alkyl which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, cyano, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, and (C 3 -C 6 )-cycloalkyl,

and

R 26 for each individual occurrence represents hydrogen or (C 1 -C 4 )-alkyl which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, cyano, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino and hydroxycarbonyl,

and

R 2 represents hydrogen, fluorine, chlorine, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxymethyl, (C 1 -C 4 )-alkoxy, trifluoromethoxy, amino or hydroxycarbonyl,

or a salt thereof.

9. The compound as claimed in claim 1 of the formula (I-A) or (I-B)

in which

R 1 represents (C 1 -C 6 )-alkyl which

(i) is mono- or disubstituted by identical or different radicals selected from the group consisting of fluorine, chlorine, cyano, trifluoromethyl, (C 3 -C 6 )-cycloalkyl, hydroxycarbonyl, —C(═O)—NR 6 R 7 , —O—C(═O)—NR 9 R 10 , NR 11 —C(═O)—R 12 , NR 13 —C(═O)—OR 14 , —NR 15 —C(═O)—NR 16 R 17 , —NR 18 —SO 2 —R 19 , —OR 23 and —NR 25 R 26

and may additionally be substituted by hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkyl amino, di-(C 1 -C 4 )-alkylamino or (C 1 -C 4 )-acylamino,

(ii) is disubstituted by identical or different radicals selected from the group consisting of hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino and (C 1 -C 4 )-acylamino in which

(a) the above-mentioned cycloalkyl radical may be substituted up to three times by identical or different substituents selected from the group consisting of fluorine, chlorine, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )-alkoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino and hydroxycarbonyl,

(b) R 7 , R 10 , R 11 , R 13 , R 15 , R 17 , R 18 and R 26 independently of one another for each individual occurrence represent a radical selected from the group consisting of hydrogen and (C 1 -C 4 )-alkyl, where (C 1 -C 4 )-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, cyano, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino and hydroxycarbonyl,

(c) R 6 , R 9 and R 14 independently of one another for each individual occurrence represent a radical selected from the group consisting of (C 1 -C 4 )-alkyl, and (C 3 -C 6 )-cycloalkyl, where

(C 3 -C 6 )-cycloalkyl may in each case be substituted up to three times by identical or different substituents selected from the group consisting of fluorine, chlorine, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )-alkoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino and hydroxycarbonyl

and

(C 1 -C 4 )-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, cyano, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, and (C 3 -C 6 )-cycloalkyl,

(d) R 12 , R 16 and R 19 independently of one another for each individual occurrence represent a radical selected from the group consisting of (C 1 -C 4 )-alkyl and (C 3 -C 6 )-cycloalkyl, where

(C 3 -C 6 )-cycloalkyl may be substituted up to three times by identical or different substituents selected from the group consisting of fluorine, chlorine, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )-alkoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino and hydroxycarbonyl

and

(C 1 -C 4 )-alkyl is mono- to trisubstituted by identical or different radicals selected from the group consisting of fluorine, chlorine, cyano, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, (C 1 -C 4 )-alkoxycarbonyl, and (C 3 -C 6 )-cyclo-alkyl,

(e) R 23 and R 25 independently of one another for each individual occurrence represent a radical selected from the group consisting of (C 1 -C 4 )-alkyl, and (C 3 -C 6 )-cycloalkyl, where

and

(C 1 -C 4 )-alkyl is mono- to trisubstituted by identical or different radicals selected from the group consisting of fluorine, chlorine, cyano, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkyl-amino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, and (C 3 -C 6 )-cycloalkyl,

and

R 2 represents hydrogen, fluorine, chlorine, cyano, trifluoromethyl, hydroxymethyl, (C 1 -C 4 )-alkoxy, trifluoromethoxy, amino or hydroxycarbonyl,

or a salt thereof.

10. The compound as claimed in claim 1 of the formula (I-A) or (I-B)

in which

R 1 represents (C 1 -C 6 )-alkoxy which is mono- or disubstituted by identical or different radicals selected from the group consisting of fluorine, chlorine, cyano, trifluoromethyl, (C 3 -C 6 )-cycloalkyl, hydroxyl, amino, hydroxycarbonyl, —C(═O)—NR 6 R 7 , —O—C(═O)—NR 9 R 10 , NR 11 C—C(—O)R 12 , NR 13 —C(═O)—OR 14 , —NR 15 —C(═O)—NR 16 R 17 , —NR 18 —SO 2 —R 19 , —OR 23 and —NR 25 R 26 in which

(i) (C 3 -C 6 )-cycloalkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )-alkoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino and hydroxycarbonyl,

(ii) R 6 , R 9 , R 12 , R 14 , R 16 , R 19 , R 23 and R 25 independently of one another for each individual occurrence represent a radical selected from the group consisting of (C 1 -C 4 )-alkyl, and (C 3 -C 6 )-cycloalkyl, where

and

where (C 1 -C 4 )-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, cyano, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino and hydroxycarbonyl,

and

R 2 represents hydrogen, fluorine, chlorine, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxymethyl, (C 1 -C 4 )-alkoxy, trifluoromethoxy, amino or hydroxycarbonyl,

or a salt thereof.

11. The compound as claimed in claim 1 of the formula (I-A) or (I-B)

in which

R 1 represents the group —C(═O)—NR 6 R 7

in which (i)

R 6 represents (C 3 -C 6 )-cycloalkyl which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )-alkoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino and hydroxycarbonyl,

represents (C 1 -C 6 )-alkyl which

(a) is mono- or disubstituted by identical or different radicals selected from the group consisting of fluorine, chlorine, cyano, trifluoromethyl, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, and (C 3 -C 6 )-cycloalkyl and may additionally be substituted by hydroxyl or (C 1 -C 4 )-alkoxy,

(b) is disubstituted by hydroxyl and/or (C 1 -C 4 )-alkoxy,

and

R 7 represents hydrogen,

or in which (ii)

R 6 represents (C 1 -C 6 )-alkyl, or (C 3 -C 6 )-cycloalkyl, where

and

(C 1 -C 6 )-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, cyano, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, hydroxycarbonyl, and (C 3 -C 6 )-cycloalkyl,

and

R 7 represents (C 1 -C 4 )-alkyl which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, cyano, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino and hydroxycarbonyl,

and

R 2 represents hydrogen, fluorine, chlorine, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxymethyl, (C 1 -C 4 )-alkoxy, trifluoromethoxy, amino or hydroxycarbonyl,

or a salt thereof.

12. A method of making a compound of the formula (I) as defined in claim 1 , comprising:

reacting a compound of the formula (II)

in which R 2 , R 3 and n have the meanings given in claim 1 and

Z 1 represents methyl or ethyl,

in an inert solvent, optionally, in the presence of an acid, with a compound of the formula (III)

in which A, R 1 and m have the meanings given in claim 1 ,

to give compounds of the formula (IV)

in which Z 1 , A, R 1 , R 2 , R 3 , m and n have the meanings given in claim 1 , which, already under these reaction conditions or in a subsequent reaction step under the influence of a base, cyclize to give at least one compound of formula (I),

and optionally converting the compound of formula (I) with an appropriate (i) solvent and/or (ii) base or acid, into a salt thereof.

13. A method of making a compound of the formula (I) as defined in claim 1 in which R 3 represents hydrogen, comprising

condensing a compound of the formula (V)

in which R 2 and n have the meanings given in claim 1 and

Z 1 represents methyl or ethyl,

with a compound of the formula (VI)

in which

Z 2 represents methyl or ethyl,

to give a compounds of the formula (VII)

in which Z 1 , R 2 and n have the meanings given above,

and reacting the compound of formula (VII) in the presence of an acid with a compound of the formula (III)

in which A, R 1 and m have the meanings given in claim 1 ,

to give compounds of the formula (IV-A)

in which Z 1 , A, R 1 , R 2 , m and n have the meanings given above,

which, already under these reaction conditions or in a subsequent reaction step under the influence of a base, cyclize to give the compounds of the formula (I) in which R 3 represents hydrogen.

14. A pharmaceutical composition comprising a compound of claim 1 in combination with an inert, non-toxic, pharmaceutically suitable auxiliary.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 5, 2010

From: THEDE, KAI; FLAMME, INGO; OEHME, FELIX; ERGUEDEN, JENS-KERIM; STOLL, FRIEDERIKE; WILD, HANNO; KOLKHOF, PETER; BECK, HARTMUT; JESKE, MARIO

To: BAYER SCHERING PHARMA AKTIENGESELLSCHAFT

Reel/Frame 023732/0843 →