ROR gamma (RORγ) modulators

Patent metadata

Field	Value
Publication number	US-10196350-B2
Application number	US-201715829226-A
Country	US
Kind code	B2
Filing date	Dec 1, 2017
Priority date	Dec 5, 2016
Publication date	Feb 5, 2019
Grant date	Feb 5, 2019

Abstract

The present application relates to compounds according to (Formula IA) or (Formula IB):

or a pharmaceutically acceptable salt thereof.

The compounds can be used as inhibitors of RORγ and are useful for the treatment of RORγ mediated diseases.

First claim

The invention claimed is:

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the absolute configuration corresponds to a compound of Formula (IA), 2-{4-[(cyclopropylmethyl)sulfonyl]phenyl}-N-{4-[(1R)-1-(difluoromethyl)-2,2,2-trifluoro-1-hydroxyethyl]phenyl}acetamide:

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the absolute configuration corresponds to a compound of Formula (IB), 2-{4-[(cyclopropylmethyl)sulfonyl]phenyl}-N-{4-[(1S)-1-(difluoromethyl)-2,2,2-trifluoro-1-hydroxyethyl]phenyl}acetamide:

4. A compound of formula (VI):

wherein the compound is selected from the group consisting of:
2-[4-(cyclopropylmethylsulfinyl)phenyl]-N-[4-[1-(difluoromethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]acetamide;
(−)-2-[4-[(S)-cyclopropylmethylsulfinyl]phenyl]-N-[4-[(1R)-1-(difluoromethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]acetamide;
(−)-2-[4-[(S)-cyclopropylmethylsulfinyl]phenyl]-N-[4-[(1S)-1-(difluoromethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]acetamide;
(+)-2-[4-[(R)-cyclopropylmethylsulfinyl]phenyl]-N-[4-[(1R)-1-(difluoromethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]acetamide; and
(+)-2-[4-[(R)-cyclopropylmethylsulfinyl]phenyl]-N-[4-[(1S)-1-(difluoromethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]acetamide,
or a pharmaceutically acceptable salt thereof.

5. A process of preparing the compound of Formula (I) according to claim 1 , comprising reacting an amine of formula (II)

with a compound of formula (III):

to generate the compound of Formula (I).

6. A method for treatment of rheumatoid arthritis, psoriasis, inflammatory bowel disease, Crohn's disease or multiple sclerosis comprising administering to a patient in need thereof an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

7. A method for treatment of rheumatoid arthritis, psoriasis, inflammatory bowel disease, Crohn's disease or multiple sclerosis comprising administering to a patient in need thereof an effective amount of the compound according to claim 4 , or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

9. The pharmaceutical composition comprising the compound according to claim 4 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

10. A method for treatment of osteoarthritis or asthma comprising administering to a patient in need thereof an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

11. A method for treatment of osteoarthritis or asthma comprising administering to a patient in need thereof an effective amount of the compound according to claim 4 , or a pharmaceutically acceptable salt thereof.

12. A method for treatment of mucosal leishmaniasis comprising administering to a patient in need thereof an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

13. A method for treatment of mucosal leishmaniasis comprising administering to a patient in need thereof an effective amount of the compound according to claim 4 , or a pharmaceutically acceptable salt thereof.

14. A method for treatment of Kawaski disease or Hashimoto's thyroiditis comprising administering to a patient in need thereof an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

15. A method for treatment of Kawaski disease or Hashimoto's thyroiditis comprising administering to a patient in need thereof an effective amount of the compound according to claim 4 , or a pharmaceutically acceptable salt thereof.

Assignees

• Lead Pharma Holding Bv
• Sanofi Sa
• Lead Pharma Holding Bv

Inventors

• Cals Joseph Maria Gerardus Barbara
• Machnik David
• Nabuurs Sander Bernardus
• Sabuco Jean-Francois

Classifications

• C07C315/04

  by reactions not involving the formation of sulfone or sulfoxide groups · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• C07C2601/02

  with a three-membered ring · CPC title

• C07C317/44

  having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title