ROR gamma (RORγ) modulators
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.
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.