New dihydroquinoline-2-one derivatives

Patent metadata

Field	Value
Publication number	US-2016002207-A1
Application number	US-201514850729-A
Country	US
Kind code	A1
Filing date	Sep 10, 2015
Priority date	Mar 8, 2013
Publication date	Jan 7, 2016
Grant date	—

Abstract

The invention provides novel compounds having the general formula (I)

wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R 11 and A are as described herein, compositions including the compounds and methods of using the compounds.

First claim

1 . Compounds of formula (I)

wherein
R 1 is H, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;
R 2 is H, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;
R 3 is H, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;
R 4 is H, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;
or R 3 and R 4 together with the carbon atoms to which they are attached form a double bond;
R 5 is H, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;
R 6 is H, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;
R 7 is H, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;
or R 6 and R 7 together with the carbon atom to which they are attached form a cycloalkyl;
A is —C(O)NR 8 —, —S—, —O—;
R 8 is H, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;
R 9 is a substituted aryl or substituted heteroaryl, wherein substituted aryl and substituted heteroaryl are substituted with one to three substitutents independently selected from H, halogen, oxo, cyano, alkyl, haloalkyl, cycloalkyl and halocycloalkyl;
R 10 is H, halogen, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;
R 11 is H, halogen, alkyl, haloalkyl, cycloalkyl or halocycloalkyl;
or pharmaceutically acceptable salts or esters.

2 . A compound according to claim 1 , wherein R 1 is alkyl.

3 . A compound according to claim 1 or 2 , wherein R 2 is H.

4 . A compound according to any one of claims 1 to 3 , wherein R 3 is H.

5 . A compound according to any one of claims 1 to 4 , wherein R 4 is H.

6 . A compound according to any one of claims 1 to 5 , wherein R 5 is H.

7 . A compound according to any one of claims 1 to 6 , wherein R 6 is H.

8 . A compound according to any one of claims 1 to 7 , wherein R 7 is H.

9 . A compound according to any one of claims 1 to 8 , wherein R 8 is H.

10 . A compound according to any one of claims 1 to 8 , wherein A is —O—.

11 . A compound according to any one of claims 1 to 10 , wherein R 9 is substituted pyridinyl, substituted pyrimidinyl or substituted benzooxazolyl, wherein substituted pyridinyl, substituted pyrimidinyl and substituted benzooxazolyl are substituted with one to three substitutents independently selected from H, halogen, cyano, alkyl and haloalkyl.

12 . A compound according to any one of claims 1 to 11 , wherein R 9 is pyridinyl, substituted pyridinyl, pyrimidinyl, substituted pyrimidinyl or benzooxazolyl, wherein substituted pyridinyl and substituted pyrimidinyl are substituted with one to three substitutents independently selected from halogen, cyano, alkyl and haloalkyl.

13 . A compound according to any one of claims 1 to 12 , wherein R 9 is pyridinyl, substituted pyridinyl, pyrimidinyl, substituted pyrimidinyl or benzooxazolyl, wherein substituted pyridinyl and substituted pyrimidinyl are substituted with one to three substitutents independently selected from halogen, cyano, alkyl and haloalkyl.

14 . A compound according to any one of claims 1 to 13 , wherein R 9 is pyridinyl substituted with one to three substitutents independently selected from halogen and alkyl.

15 . A compound according to any one of claims 1 to 14 , wherein R 9 is methylpyridinyl, chloropyridinyl or fluoropyridinyl.

16 . A compound according to any one of claims 1 to 15 , wherein R 9 is methyl, chloropyridinyl or fluoropyridinyl.

17 . A compound according to any one of claims 1 to 16 , wherein R 10 is H or alkyl.

18 . A compound according to any one of claims 1 to 17 , wherein R 10 is alkyl.

19 . A compound according to any one of claims 1 to 18 , wherein R 11 is H or halogen.

20 . A compound according to any one of claims 1 to 19 , wherein R 11 is halogen.

21 . A compound according to any one of claims 1 to 20 , selected from
6-[5-(6-Chloro-pyridin-2-yloxymethyl)-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;
6-[5-(5-Fluoro-pyridin-2-yloxymethyl)-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;
1-Methyl-6-[5-(6-methyl-pyridin-2-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
1-Methyl-6-[5-(4-methyl-6-trifluoromethyl-pyridin-2-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
1-Methyl-6-[5-(4-methyl-pyridin-2-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
6-[5-(5-Chloro-pyridin-2-yloxymethyl)-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;
1-Methyl-6-[5-(pyridin-2-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
1-Methyl-6-[5-(3-trifluoromethyl-pyridin-2-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
1-Methyl-6-[5-(2-methyl-pyrimidin-4-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
1-Methyl-6-[5-(2-trifluoromethyl-pyrimidin-4-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
6-[5-(2-Chloro-pyrimidin-5-yloxymethyl)-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;
1-Methyl-6-[5-(pyrimidin-2-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
6-[5-(Benzooxazol-2-ylsulfanylmethyl)-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;
1-Methyl-6-[5-(6-methyl-pyridin-2-ylsulfanylmethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
1-Methyl-6-[5-(3-trifluoromethyl-pyridin-2-ylsulfanylmethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
6-[5-(3-Chloro-pyridin-2-ylsulfanylmethyl)-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;
2-[5-(1-Methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylmethoxy]-isonicotinonitrile;
6-[5-(6-Fluoro-pyridin-2-yloxymethyl)-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;
7-Fluoro-6-[5-(3-fluoro-pyridin-2-yloxymethyl)-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;
6-[5-(5-Chloro-pyridin-2-yloxymethyl)-pyridin-3-yl]-7-fluoro-1-methyl-3,4-dihydro-1H-quinolin-2-one;
6-[5-(6-Chloro-pyridin-2-yloxymethyl)-pyridin-3-yl]-7-fluoro-1-methyl-3,4-dihydro-1H-quinolin-2-one;
7-Fluoro-1-methyl-6-[5-(6-methyl-pyridin-2-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
7-Fluoro-1-methyl-6-[5-(4-methyl-pyridin-2-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
7-Fluoro-1-methyl-6-[4-methyl-5-(6-methyl-pyridin-2-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
6-[5-(6-Chloro-pyridin-2-yloxymethyl)-4-methyl-pyridin-3-yl]-7-fluoro-1-methyl-3,4-dihydro-1H-quinolin-2-one;
7-Fluoro-6-[5-(3-fluoro-pyridin-2-yloxymethyl)-4-methyl-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;
7-Fluoro-6-[5-(6-fluoro-pyridin-2-yloxymethyl)-4-methyl-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;
2-[5-(1-Methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-yl]-N-(6-methyl-pyridin-2-yl)-acetamide;
N-(3-Chloro-phenyl)-2-[5-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-yl]-acetamide;
N-(6-Chloro-pyridin-2-yl)-2-[5-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-yl]-acetamide;
and pharmaceutically acceptable salts thereof.

22 . A compound according to any one of claims 1 to 21 , selected from
7-Fluoro-1-methyl-6-[5-(6-methyl-pyridin-2-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
7-Fluoro-1-methyl-6-[4-methyl-5-(6-methyl-pyridin-2-yloxymethyl)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one;
6-[5-(6-Chloro-pyridin-2-yloxymethyl)-4-methyl-pyridin-3-yl]-7-fluoro-1-methyl-3,4-dihydro-1H-quinolin-2-one;
7-Fluoro-6-[5-(3-fluoro-pyridin-2-yloxymethyl)-4-methyl-pyridin-3-yl]-1-methyl-3,4-dihy

Assignees

• Hoffmann La Roche

Inventors

• Aebi Johannes
• Amrein Kurt
• Hornsperger Benoit
• Kuhn Bernd
• Maerki Hans P
• Mayweg Alexander V
• Tan Xuefei

Classifications

• A61P5/40

  Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P5/46

  for decreasing, blocking or antagonising the activity of glucocorticosteroids · CPC title

• A61P5/42

  for decreasing, blocking or antagonising the activity of mineralocorticosteroids · CPC title