Phenoxymethyl derivatives

Patent metadata

Field	Value
Publication number	US-10640472-B2
Application number	US-201815910307-A
Country	US
Kind code	B2
Filing date	Mar 2, 2018
Priority date	Sep 4, 2015
Publication date	May 5, 2020
Grant date	May 5, 2020

Abstract

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

wherein R A , R B , R C , R C1 and W are as defined 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 A is C 1 -C 6 -alkyl;
R B is cyano;
R C and R C1 are independently selected from the group consisting of H, halogen, and C 1 -C 6 -alkyl;
W is ring system A:

and R D1 is C 1 -C 6 -alkyl;
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R A is isopropyl or tert-butyl.

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R C is H or halogen.

4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R C1 is halogen.

5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R A is isopropyl.

6. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R A is tert-butyl.

7. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R C is H.

8. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R C is C 1 -C 6 -alkyl.

9. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R C1 is H.

10. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R D1 is methyl.

11. The compound according to claim 1 , wherein the compound is of formula I(b),

wherein R A , R B , R C , and R D1 are as defined for formula (I), or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 , wherein the compound is:
4-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]-3-propan-2-ylbenzonitrile;
2-methyl-4-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]-5-propan-2-ylbenzonitrile;
3-tert-butyl-4-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]benzonitrile;
5-tert-butyl-2-methyl-4-[(4-methyl-5-oxo 1H-1,2,4-triazol-3-yl)methoxy]benzonitrile;
4-tert-butyl-2-methyl-5-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]benzonitrile; or
4-tert-butyl-3-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]benzonitrile;
or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 , wherein the compound is:
4-tert-butyl-2-chloro-5-((4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy)benzonitrile;
5-tert-butyl-2-chloro-4-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]benzonitrile; or
5-tert-butyl-2-fluoro-4-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]benzonitrile,
or a pharmaceutically acceptable salt thereof.

14. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

15. A compound according to claim 1 of formula (I), or a pharmaceutically acceptable salt thereof, when manufactured by the process comprising the reaction of a compound of formula (II) in the presence of a compound of formula (III),

wherein X is halogen, mesylate, or tosylate;
and R A , R B , R C , and W are as defined in formula (I).

16. A pharmaceutical composition comprising a compound according to claim 12 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

17. A pharmaceutical composition comprising a compound according to claim 13 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

18. The compound according to claim 13 , wherein the compound is 4-tert-butyl-2-chloro-5-((4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy)benzonitrile, or a pharmaceutically acceptable salt thereof.

19. A pharmaceutical composition comprising a compound according to claim 18 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

20. The compound according to claim 13 , wherein the compound is 5-tert-butyl-2-chloro-4-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]benzonitrile, or a pharmaceutically acceptable salt thereof.

21. A pharmaceutical composition comprising a compound according to claim 20 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

22. The compound according to claim 13 , wherein the compound is 5-tert-butyl-2-fluoro-4-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]benzonitrile, or a pharmaceutically acceptable salt thereof.

23. A pharmaceutical composition comprising a compound according to claim 22 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

Assignees

• Hoffmann La Roche

Inventors

• Hert Jerome
• Hunziker Daniel
• Kuehne Holger
• Luebbers Thomas
• Martin Rainer E
• Mattei Patrizio
• Neidhart Werner
• Richter Hans
• Rudolph Markus
• Pinard Emmanuel

Classifications

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D407/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D231/12

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D249/08 Primary

  1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles · CPC title

• A61P27/02

  Ophthalmic agents · CPC title