Phenoxymethyl derivatives

• US 10,640,472 B2
• Filed: 03/02/2018
• Issued: 05/05/2020
• Est. Priority Date: 09/04/2015
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Hert, Jerome, Hunziker, Daniel, Kuehne, Holger, Luebbers, Thomas, Martin, Rainer E., Mattei, Patrizio, Neidhart, Werner, Richter, Hans, Rudolph, Markus, Pinard, Emmanuel
• Primary Examiner(s): Coughlin, Matthew P
• Assistant Examiner(s): Patel, Sagar
• Application Number:
  US15/910,307
• Publication Number:
  US 20180201588A1
• Time in Patent Office: 795 Days
• Field of Search: 514383, 514359, 514406, 514247, 5482682, 548255, 5483761, 5483605, 5483625, 544239
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: C07B 41/04 of ether, acetal or ketal groups
• CPC Class Codes: C07C 205/04 containing six-membered aromatic rings
• CPC Class Codes: C07C 255/50 to carbon atoms of non-condensed six-membered aromatic rings
• CPC Class Codes: C07C 317/14 having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 231/20 One oxygen atom attached in position 3 or 5
• CPC Class Codes: C07D 231/56 Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 237/14 Oxygen atoms
• CPC Class Codes: C07D 249/04 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
• CPC Class Codes: C07D 249/08 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 249/12 Oxygen or sulfur atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 407/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 407/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07F 7/0812 : comprising a heterocyclic ring

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.

Claims

1. A compound of formula (I):

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 C₁-C₆-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),

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),

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.