Pteridine derivatives as modulators of ROR gamma

Patent metadata

Field	Value
Publication number	US-10450314-B2
Application number	US-201615763690-A
Country	US
Kind code	B2
Filing date	Sep 28, 2016
Priority date	Oct 1, 2015
Publication date	Oct 22, 2019
Grant date	Oct 22, 2019

Abstract

The present invention encompasses compounds of formula (I) wherein the variables are defined herein which are suitable for the modulation of RORγ and the treatment of diseases related to the modulation of RORγ. The present invention also encompasses processes of making compounds of formula (I) and pharmaceutical preparations containing them.

First claim

What is claimed is:

1. A compound of formula (I)

wherein:
R′ is selected from —S(O) n R 6 , —S(O) n NR 7 R 8 , and —S(O)(NH)R 6 ;
wherein:
R 6 is:
C 1-3 alkyl
R 7 and R 8 are each H; and
n is 1 or 2;

R 2 and R 3 are independently selected from
C 1-3 alkyl;
cyclopropyl; and
methoxy;
R 4 is C 1-6 alkyl, optionally substituted with one or two groups independently selected from
C 3-6 cycloalkyl;
halogen;
—CF 3 ; and
—CN;
R 5 is selected from
C 1-3 alkyl, optionally substituted with 1 to 3 fluoro groups;
—CH 2 OH;
—CH 2 OC(O)C 1-3 alkyl; and
—OC 1-3 alkyl;
W is selected from
pyridinyl;
pyrimidinyl;
pyrizinyl;
phenyl; and
piperidinyl;
and the pharmaceutically acceptable salts thereof.

2. The compound of formula (I) according to claim 1 , wherein
R 1 is selected from —S(O) n R 6 , —S(O) n NR 7 R 8 , and —S(O)(NH)R 6 ;
wherein:
R 6 is C 1-3 alkyl;
R 7 and R 8 are each H; and
n is 2;

R 2 and R 3 are independently selected from
methyl;
cyclopropyl; and
methoxy;
R 4 is C 1-4 alkyl, optionally substituted with one or two groups independently selected from
cyclopropyl;
—F;
—CF 3 ; and
—CN;
R 5 is selected from
—CH 3 ;
—CH 2 F;
—CH 2 OH;
—CH 2 OC(O)CH 3 ; and
—OCH 3 ;
W is selected from
2-pyridinyl, 3-pyridinyl, 2-pyrimidinyl, 2-pyrizinyl and phenyl;
and the pharmaceutically acceptable salts thereof.

3. The compound of formula (I) according to claim 1 , wherein
R 1 is selected from —S(O) n R 6 , —S(O) n NR 7 R 8 , and —S(O)(NH)R 6 ;
wherein:
R 6 is C 1-2 alkyl;
R 7 and R 8 are each —H; and
n is 2;

R 2 and R 3 are independently selected from
methyl;
cyclopropyl; and
methoxy;
R 4 is C 1-4 alkyl, optionally substituted with one or two groups independently selected from
cyclopropyl;
—F;
—CF 3 ; and
—CN;
R 5 is selected from
—CH 3 ;
—CH 2 F;
—CH 2 OH;
—CH 2 OC(O)CH 3 ; and
—OCH 3 ;
W is selected from
2-pyridinyl, 3-pyridinyl, 2-pyrimidinyl, 2-pyrizinyl and phenyl;
and the pharmaceutically acceptable salts thereof.

4. The compound of formula (I) according to claim 1 , wherein
R 1 is selected from —S(O) n R 6 , —S(O) n NR 7 R 8 , and —S(O)(NH)R 6 ;
wherein:
R 6 is C 1-2 alkyl;
R 7 and R 8 are each —H; and
n is 2;

R 2 is methyl or methoxy;
R 3 is cyclopropyl;
R 4 is C 1-4 alkyl, optionally substituted with a group selected from
cyclopropyl and —CF 3 ;
R 5 is selected from
—CH 3 ;
—CH 2 F; and
—CH 2 OH;
W is selected from
2-pyridinyl, 3-pyridinyl, 2-pyrimidinyl, and phenyl;
and the pharmaceutically acceptable salts thereof.

5. The compound of formula (I) according to claim 1 , wherein
R 2 is methyl or methoxy;
R 3 is cyclopropyl;
R 4 is C 1-4 alkyl, optionally substituted with a group selected from
cyclopropyl and —CF 3 ;
R 5 is —CH 3 ;
W is selected from
2-pyridinyl, 3-pyridinyl, 2-pyrimidinyl, and phenyl;
and the pharmaceutically acceptable salts thereof.

6. The compound of formula (I) according to claim 1 , wherein
W is selected from 2-pyridinyl and, 3-pyridinyl;
and the pharmaceutically acceptable salts thereof.

7. The compound according to claim 1 selected from the group consisting of:

and the pharmaceutically acceptable salts thereof.

8. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient or carrier.

9. A method for treating an autoimmune disease or allergic disorder wherein the activity of RORγ modulators would be of therapeutic benefit, comprising administering to a patient having such autoimmune disease or allergic disorder a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof.

Assignees

• Boehringer Ingelheim Int
• Brunette Steven Richard
• Csengery Johanna
• Hughes Robert Owen
• Li Xiang
• Sibley Robert
• Turner Michael Robert
• Xiong Zhaoming

Inventors

• Brunette Steven Richard
• Csengery Johanna
• Hughes Robert Owen
• Li Xiang
• Sibley Robert
• Turner Michael Robert
• Xiong Zhaoming

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title