6-aminopyridin-3-yl thiazoles as modulators of RORγT

Patent metadata

Field	Value
Publication number	US-10975068-B2
Application number	US-201715497565-A
Country	US
Kind code	B2
Filing date	Apr 26, 2017
Priority date	Apr 27, 2016
Publication date	Apr 13, 2021
Grant date	Apr 13, 2021

Abstract

The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein the syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula I.

First claim

We claim:

1. A compound of Formula I:

wherein
R 1 is H, —C (1-3) alkyl, —CHF 2 , —CF 3 , —CN, —OCH 3 , —OCH 2 CH 3 , cyclopropyl, OCF 3 , or OCHF 2 ;
R 2 is H, F, —CHF 2 , —CF 3 , —CN, —OCH 3 , —OCHF 2 , or OCF 3 ; provided that R 2 may not be H if R 1 is H;
A 1 and A 2 are taken together with their attached nitrogen to form a ring selected from the group consisting of

A 3 is H, —C (1-6) alkyl,

—SO 2 CH(CH 3 ) 2 , —SO 2 CH 3 ,

wherein said —C (1-6) alkyl is optionally substituted with one —NH 2 group, one or two —OH groups, and may be additionally substituted with up to six fluorine atoms;
A 4 is —H, or —CH 3 ;
A 5 is —C (4-6) cycloalkyl, —C (1-6) alkyl,

wherein said —C (1-6) alkyl and —C (4-6) cycloalkyl are optionally substituted with up to three fluorine atoms; and said —C (1-6) alkyl is independently optionally substituted with one cyclobutyl, or up to two cyclopropyl groups;
and a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein:
A 5 is —C (3-6) alkyl,

wherein said —C (3-6) alkyl and —C (4-6) cycloalkyl are optionally substituted with up to three fluorine atoms;
and a pharmaceutically acceptable salt thereof.

3. The compound of claim 2 wherein:
R 1 is H, —C (1-3) alkyl, —CHF 2 , —CF 3 , —CN, —OCH 3 , —OCH 2 CH 3 , or cyclopropyl;
R 2 is H, F, —CHF 2 , —CF 3 , —CN, —OCH 3 , or —OCHF 2 ; provided that R 2 may not be H if R 1 is H;
and a pharmaceutically acceptable salt thereof.

4. The compound of claim 3 selected from the group consisting of:

and a pharmaceutically acceptable salt thereof.

5. The compound of claim 3 selected from the group consisting of:

and a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

7. A method for treating or ameliorating a RORγt mediated inflammatory syndrome, disorder or disease selected from the group consisting of: inflammatory bowel diseases, rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disorder, psoriatic arthritis, ankylosing spondylitis, neutrophilic asthma, steroid resistant asthma, multiple sclerosis, and systemic lupus erythematosus, comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .

8. A method for treating or ameliorating a RORγt mediated inflammatory syndrome, disorder or disease selected from the group consisting of: depression and metabolic syndrome, comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Goldberg Steven
• Mcclure Kelly
• Tanis Virginia M
• Fennema Elizabeth G
• Lebsack Alec D
• Martin Connor L
• Venkatesan Hariharan
• Xue Xiaohua
• Woods Craig R

Classifications

• C07D417/04 Primary

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

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• C07D487/08

  Bridged systems · CPC title

• A61P19/02

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

• C07D498/08

  Bridged systems · CPC title