3,4-dihydro-2H-isoquinoline-1-one and 2,3-dihydro-isoindol-1-one compounds

Patent metadata

Field	Value
Publication number	US-9695151-B2
Application number	US-201514947760-A
Country	US
Kind code	B2
Filing date	Nov 20, 2015
Priority date	May 27, 2013
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

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 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , A, m, n and p are as described herein, compositions including the compounds and methods of using the compounds.

First claim

The invention claimed is:

1. A Compound of formula (I)

wherein
R 1 , R 2 , R 3 and R 4 are independently selected from H, alkyl and cycloalkyl;
R 5 , R 7 and R 9 are independently selected from H and alkyl;
R 8 (i) is hydrogen and both R 6 and R 9 together are —CH 2 —, and, R 10 and R 11 together are —CH 2 —; or,
(ii) and R 6 , R 9 and R 11 are independently H or alkyl, and R 10 is H; or,
(iii) and R 6 and R 9 are independently H or alkyl and R 10 and R 11 together are —CH 2 —; or,
(iv) and R 11 together are —CH 2 —CH 2 —; and R 6 and R 10 are independently H or alkyl;

A is —C(O)— or —S(O) 2 —;
R 12 is alkyl;
R 13 is halogen or cyano;
R 14 is H, alkylor cycloalkyl;
R 15 is H, alkyl, cycloalkyl or halogen;
m, n and p are independently selected from zero and 1;
w is 1, 2 or 3;
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein
R 1 and R 2 are alkyl;
R 7 and R 9 are H;
R 8 and R 11 together form —CH 2 —CH 2 —;
R 10 is H or R 10 and R 11 together form —(CH 2 ) w —;
A is —C(O)— or —S(O) 2 —;
R 12 is alkyl;
R 13 is halogen;
R 14 is H or alkyl;
R 15 is H;
m and n are zero;
p is zero or 1;
w is 1 or 2;
or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 wherein
R 1 and R 2 are alkyl;
R 7 and R 9 are H;
R 8 and R 11 together form —CH 2 —CH 2 —;
R 10 is H or R 10 and R 11 together form —(CH 2 ) w —;
A is —S(O) 2 —;
R 12 is alkyl;
R 13 is halogen;
R 14 is H or alkyl;
R 15 is H
m and n are zero;
p is zero or 1;
w is 1 or 2;
or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 wherein
R 1 and R 2 are alkyl;
R 7 and R 9 are H;
R 8 and R 11 together form —CH 2 —CH 2 —;
R 10 is H;
A is —S(O) 2 —;
R 12 is alkyl;
R 13 is chloro;
R 14 is H;
R 15 is H
m and n are zero;
p is 1;
or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 wherein
R 1 and R 2 are methyl;
R 7 and R 9 are H;
R 8 and R 11 together form —CH 2 —CH 2 —;
R 10 is H;
A is —S(O) 2 —;
R 12 is ethyl;
R 13 is chloro;
R 14 is H or alkyl;
R 15 is H
m and n are zero;
p is 1;
or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 , wherein A is —S(O) 2 —.

7. The compound according to claim 1 wherein R 1 and R 2 are independently selected from H and alkyl.

8. The compound according to claim 1 wherein R 1 and R 2 are alkyl.

9. The compound according to claim 1 wherein R 1 and R 2 are methyl.

10. The compound according to claim 1 wherein m and n are zero.

11. The compound according to claim 1 wherein p is 1.

12. The compound according to claim 1 wherein w is 1 or 2.

13. The compound according to claim 1 wherein R 5 , R 7 and R 9 are H.

14. The compound according to claim 1 wherein R 9 is H.

15. The compound according to claim 1 , wherein R 12 is methyl, ethyl, propyl or isopropyl.

16. The compound according to claim 1 wherein R 12 is ethyl, propyl or isopropyl.

17. The compound according to claim 1 wherein R 12 is ethyl.

18. The compound according to claim 1 wherein R 13 is chloro.

19. The compound according to claim 1 wherein R 15 is H.

20. The compound according to claim 1 selected from
2-[5-[(1-Acetylazetidin-3-yl)amino]pyridin-3-yl]-5-chloro-3,3-dimethylisoindol-1-one;
2-[5-[(1-Acetylazetidin-3-yl)-methylamino]pyridin-3-yl]-5-chloro-3,3-dimethylisoindol-1-one;
5-Chloro-2-[5-[[(3R or 3S)-1-ethylsulfonylpyrrolidin-3-yl]-methylamino]pyridin-3-yl]-3,3-dimethylisoindol-1-one;
5-Chloro-2-[5-[[(3S or 3R)-1-ethylsulfonylpyrrolidin-3-yl]-methylamino]pyridin-3-yl]-3,3-dimethylisoindol-1-one;
2-[5-[(1-Acetylpiperidin-4-yl)amino]pyridin-3-yl]-5-chloro-3,3-dimethylisoindol-1-one;
5-Chloro-2-[5-[(1-ethylsulfonylpiperidin-4-yl)amino]pyridin-3-yl]-3,3-dimethylisoindol-1-one;
5-Chloro-2-[5-[(1-ethylsulfonylazetidin-3-yl)amino]pyridin-3-yl]-3,3-dimethylisoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[(1-methylsulfonylazetidin-3-yl)amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[(1-propanoylazetidin-3-yl)amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-2-[5-[(1-ethylsulfonylazetidin-3-yl)-methylamino]pyridin-3-yl]-3,3-dimethylisoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[methyl-(1-methylsulfonylazetidin-3-yl)amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[methyl-(1-propanoylazetidin-3-yl)amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[methyl-(1-propan-2-ylsulfonylazetidin-3-yl)amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[methyl-(1-propylsulfonylazetidin-3-yl)amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[methyl-[(3S or 3R)-1-propan-2-ylsulfonylpyrrolidin-3-yl]amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[methyl-[(3R or 3S)-1-propan-2-ylsulfonylpyrrolidin-3-yl]amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[methyl-[(3S or 3R)-1-propylsulfonylpyrrolidin-3-yl]amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[methyl-[(3R or 3 S)-1-propylsulfonylpyrrolidin-3-yl]amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[methyl-(1-propanoylpiperidin-4-yl)amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-2-[5-[(1-ethylsulfonylpiperidin-4-yl)-methylamino]pyridin-3-yl]-3,3-dimethylisoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[methyl-(1-methylsulfonylpiperidin-4-yl)amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[[(3R or 3 S)-1-methylsulfonylpiperidin-3-yl]amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[[(3S or 3R)-1-methylsulfonylpiperidin-3-yl]amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-2-[5-[[(3R or 3 S)-1-ethylsulfonylpiperidin-3-yl]amino]pyridin-3-yl]-3,3-dimethylisoindol-1-one;
5-Chloro-2-[5-[[(3S or 3R)-1-ethylsulfonylpiperidin-3-yl]amino]pyridin-3-yl]-3,3-dimethylisoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[[(3R or 3 S)-1-propan-2-ylsulfonylpiperidin-3-yl]amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[[(3S or 3R)-1-propan-2-ylsulfonylpiperidin-3-yl]amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-2-[5-[(1-propanoylazetidin-3-yl)amino]pyridin-3-yl]-3H-isoindol-1-one;
6-Chloro-2-[5-[(1-propanoylazetidin-3-yl)amino]pyridin-3-yl]-3,4-dihydroisoquinolin-1-one;
6-Chloro-2-[5-[(1-ethylsulfonylazetidin-3-yl)amino]pyridin-3-yl]-3,4-dihydroisoquinolin-1-one;
6-Chloro-2-[5-[(1-propan-2-ylsulfonylazetidin-3-yl)amino]pyridin-3-yl]-3,4-dihydroisoquinolin-1-one;
2-[5-[(1-Acetylazetidin-3-yl)amino]pyridin-3-yl]-6-chloro-3,4-dihydroisoquinolin-1-one;
5-Chloro-3-methyl-2-[5-[(1-propanoylazetidin-3-yl)amino]pyridin-3-yl]-3H-isoindol-1-one;
5-Chloro-2-[5-[(1-ethylsulfonylazetidin-3-yl)amino]pyridin-3-yl]-3-methyl-3H-isoindol-1-one;
2-[5-[(2-Acetyl-2-azaspiro[3.3]heptan-6-yl)amino]pyridin-3-yl]-5-chloro-3,3-dimethylisoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[(2-propanoyl-2-azaspiro[3.3]heptan-6-yl)amino]pyridin-3-yl]isoindol-1-one;
5-Chloro-2-[5-[(2-ethylsulfonyl-2-azaspiro[3.3]heptan-6-yl)amino]pyridin-3-yl]-3,3-dimethylisoindol-1-one;
5-Chloro-3,3-dimethyl-2-[5-[(2-propan-2-ylsulfonyl-2-azaspiro[3.3]heptan-6-yl)amino]pyridin-3-yl]isoindol-1-one;
(3R or 3S)-5-Chloro-3-methyl-2-[5-[(1-propanoylazetidin-3-yl)amino]-3-pyridyl]isoindolin-1-o

Assignees

• Hoffmann La Roche

Inventors

• Aebi Johannes
• Amrein Kurt
• Chen Wenming
• Hornsperger Benoit
• Kuhn Bernd
• Liu Yongfu
• Maerki Hans P
• Martin Rainer E
• Mayweg Alexander
• Tan Xuefei
• Wang Lisha
• Zhou Mingwei

Classifications

• A61P5/46

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

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P5/42

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

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title