Heterocyclic compound

Patent metadata

Field	Value
Publication number	US-2016159773-A1
Application number	US-201414909427-A
Country	US
Kind code	A1
Filing date	Jul 29, 2014
Priority date	Jul 30, 2013
Publication date	Jun 9, 2016
Grant date	—

Abstract

The present invention provides an agent for the prophylaxis or treatment of autoimmune diseases (e.g., psoriasis, rheumatoid arthritis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus etc.) and the like, which has a superior Tyk2 inhibitory action.
The present invention relates to a compound represented by the formula

wherein each symbol is as defined in the specification, or a salt thereof.

First claim

1 . A compound represented by the formula (I):

wherein
Ring A is an optionally further substituted pyrrolidine ring;
R 1 , R 2 and R 4 are independently a hydrogen atom or a substituent;
R 3 is a hydrogen atom, a halogen atom, an optionally halogenated C 1-6 alkyl group, a mono- or di-(optionally halogenated C 1-6 alkyl)amino group or an amino group; and
R 5 is a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 6-14 aryl group, an optionally substituted aromatic heterocyclic group or an acyl group,
or a salt thereof.

2 . The compound or salt of claim 1 , wherein R 3 is a hydrogen atom or an amino group.

3 . The compound or salt of claim 1 , wherein
R 1 is an optionally substituted C 1-6 alkyl group or an optionally substituted C 3-10 cycloalkyl group; R 2 and R 4 are independently a hydrogen atom, a halogen atom or an optionally substituted C 1-6 alkyl group; R 3 is a hydrogen atom or an amino group; and R 5 is (1) a hydrogen atom, (2) an optionally substituted C 3-10 cycloalkyl-carbonyl group, (3) an optionally substituted C 6-14 aryl group, (4) an optionally substituted 5- to 14-membered aromatic heterocyclic group, (5) an optionally substituted C 1-6 alkyl-carbonyl group, (6) an optionally substituted C 6-14 aryl-carbonyl group, (7) an optionally substituted 5- or 6-membered aromatic heterocyclylcarbonyl group, (8) an optionally substituted C 1-6 alkyl-carbamoyl group, (9) an optionally substituted C 6-14 aryl-carbamoyl group, (10) an optionally substituted C 3-10 cycloalkyl-carbamoyl group, or (11) an optionally substituted 3- to 8-membered monocyclic non-aromatic heterocyclylcarbamoyl group.

4 . (3S)-3-Cyclopropyl-1-(2-((5-(morpholin-4-yl)pyridin-2-yl)amino)pyridin-4-yl)-2-oxopyrrolidine-3-carbonitrile or a salt thereof.

5 . (3S)-3-Cyclopropyl-1-(2-((5-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)pyridin-4-yl)-2-oxopyrrolidine-3-carbonitrile or a salt thereof.

6 . 3-((4-((3S)-3-Cyano-3-cyclopropyl-2-oxopyrrolidin-1-yl)pyridin-2-yl)amino)-N,1-dimethyl-1H-pyrazole-5-carboxamide or a salt thereof.

7 . A medicament comprising the compound or salt of claim 1 .

8 . The medicament of claim 7 , which is a tyrosine kinase 2 inhibitor.

9 . The medicament of claim 7 , which is an agent for the prophylaxis or treatment of autoimmune diseases.

10 . The medicament of claim 9 , wherein the autoimmune disease is psoriasis, rheumatoid arthritis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis or systemic lupus erythematosus.

11 . The compound or salt of claim 1 for use in the prophylaxis or treatment of autoimmune diseases.

12 . The compound or salt of claim 11 , wherein the autoimmune disease is psoriasis, rheumatoid arthritis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis or systemic lupus erythematosus.

13 . A method of inhibiting tyrosine kinase 2 in a mammal, which comprises administering an effective amount of the compound or salt of claim 1 to the mammal.

14 . A method for the prophylaxis or treatment of autoimmune diseases in a mammal, which comprises administering an effective amount of the compound or salt of claim 1 to the mammal.

15 . The method of claim 14 , wherein the autoimmune disease is psoriasis, rheumatoid arthritis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis or systemic lupus erythematosus.

16 .- 17 . (canceled)

Assignees

• Takeda Pharmaceutical

Inventors

• Saitoh Morihisa
• Yogo Takatoshi
• Kamei Taku
• Tokunaga Norihito
• Ohba Yusuke
• Yukawa Takafumi

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

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

• A61P27/02

  Ophthalmic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title