Kinase inhibitors

Patent metadata

Field	Value
Publication number	US-9994565-B2
Application number	US-201615388050-A
Country	US
Kind code	B2
Filing date	Dec 22, 2016
Priority date	Dec 23, 2015
Publication date	Jun 12, 2018
Grant date	Jun 12, 2018

Abstract

Compounds of formula (I) defined herein are p38 MAPK inhibitors and are useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.

First claim

The invention claimed is:

1. A compound, which is selected from the group consisting of:
N-[5-tert-Butyl-3-(3-{(1S,4R)-4-[3-(1-dimethylamino-1-methyl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide;
N-[5-tert-Butyl-2-methoxy-3-(3-{(1S,4R)-4-[3-((S)-1-methyl-piperidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide;
N-[5-tert-Butyl-3-(3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide;
N-[5-tert-Butyl-3-(3-{(1S,4R)-4-[3-((S)-1-isopropyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide hydrochloride salt;
N-[5-tert-Butyl-3-(3-{(1S,4R)-4-[3-((S)-1-dimethylamino-2-methyl-propyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide;
N-[5-tert-Butyl-3-(3-{(1S,4R)-4-[3-((R)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide;
N-[5-tert-Butyl-3-(3-{(1S,4R)-4-[3-((2S,5S)-1,5-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide;
N-[5-tert-Butyl-3-(3-{(1S,4S)-4-[3-((2S,5S)-1,5-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; and
N-[5-tert-Butyl-3-(3-{(1S,4S)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl) [1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}ureido) 2-methoxy-phenyl]-methanesulfonamide
or a pharmaceutically acceptable salt of said compound.

2. A method of treating a disease or condition selected from the group consisting of chronic eosinophilic pneumonia, asthma, COPD, adult respiratory distress syndrome, exacerbation of airways hyper-reactivity consequent to other drug therapy, or airways disease that is associated with pulmonary hypertension, said method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt according to claim 1 .

3. A pharmaceutical composition, comprising a compound or pharmaceutically acceptable salt according to claim 1 and one or more pharmaceutically acceptable carriers.

4. A method of inhibiting p38 MAP kinase activity, said method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt according to claim 1 .

5. A method according to claim 2 , wherein said disease or condition is chronic eosinophilic pneumonia.

6. A method according to claim 2 , wherein said disease or condition is chronic asthma.

7. A method according to claim 2 , wherein said disease or condition is COPD.

8. A method according to claim 2 , wherein said disease or condition is adult respiratory distress syndrome.

9. A method according to claim 2 , wherein said disease or condition is exacerbation of airways hyper-reactivity consequent to other drug therapy.

10. A method according to claim 2 , wherein said disease or condition is airways disease that is associated with pulmonary hypertension.

Assignees

• Chiesi Farm Spa

Inventors

• Capaldi Carmelida
• Armani Elisabetta
• Jennings Andrew Steven Robert
• Hurley Christopher

Classifications

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title