Pteridine derivatives as modulators of ROR gamma

• US 10,450,314 B2
• Filed: 09/28/2016
• Issued: 10/22/2019
• Est. Priority Date: 10/01/2015
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Brunette, Steven Richard, Csengery, Johanna, Hughes, Robert Owen, Li, Xiang, Sibley, Robert, Turner, Michael Robert, Xiong, Zhaoming
• Primary Examiner(s): Cheng, Karen
• Application Number:
  US15/763,690
• Publication Number:
  US 20180298005A1
• Time in Patent Office: 1,119 Days
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 475/00 Heterocyclic compounds containing pteridine ring systems
• CPC Class Codes: C07D 475/10 : with an aromatic or hetero-aromatic ring directly attached in position 2

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.

Claims

1. A compound of formula (I)

2. The compound of formula (I) according to claim 1, wherein

R¹ is selected from —

S(O)_nR⁶, —

S(O)_nNR⁷R⁸, and —

S(O)(NH)R⁶;

wherein;

R⁶ is C_1-3 alkyl;

R⁷ and R⁸ are each H; and

n is 2;

R² and R³ are independently selected from

methyl;

cyclopropyl; and

methoxy;

R⁴ is C_1-4alkyl, optionally substituted with one or two groups independently selected from

cyclopropyl;

—

F;

—

CF₃; and

—

CN;

R⁵ is selected from

—

CH₃;

—

CH₂F;

—

CH₂OH;

—

CH₂OC(O)CH₃; and

—

OCH₃;

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

R¹ is selected from —

S(O)_nR⁶, —

S(O)_nNR⁷R⁸, and —

S(O)(NH)R⁶;

wherein;

R⁶ is C_1-2 alkyl;

R⁷ and R⁸ are each —

H; and

n is 2;

R² and R³ are independently selected from

methyl;

cyclopropyl; and

methoxy;

R⁴ is C_1-4alkyl, optionally substituted with one or two groups independently selected from

cyclopropyl;

—

F;

—

CF₃; and

—

CN;

R⁵ is selected from

—

CH₃;

—

CH₂F;

—

CH₂OH;

—

CH₂OC(O)CH₃; and

—

OCH₃;

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

R¹ is selected from —

S(O)_nR⁶, —

S(O)_nNR⁷R⁸, and —

S(O)(NH)R⁶;

wherein;

R⁶ is C_1-2 alkyl;

R⁷ and R⁸ are each —

H; and

n is 2;

R² is methyl or methoxy;

R³ is cyclopropyl;

R⁴ is C_1-4alkyl, optionally substituted with a group selected from

cyclopropyl and —

CF₃;

R⁵ is selected from

—

CH₃;

—

CH₂F; and

—

CH₂OH;

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

R² is methyl or methoxy;

R³ is cyclopropyl;

R⁴ is C_1-4alkyl, optionally substituted with a group selected from

cyclopropyl and —

CF₃;

R⁵ is —

CH₃;

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:

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.