Bicyclic-fused heteroaryl or aryl compounds

Patent metadata

Field	Value
Publication number	US-10793579-B2
Application number	US-201916411679-A
Country	US
Kind code	B2
Filing date	May 14, 2019
Priority date	Apr 4, 2014
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

Abstract

Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula Ia,

as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

First claim

We claim:

1. A pharmaceutical combination comprising 1-(((2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl)methoxy)-7-methoxyisoquinoline-6-carboxamide, or a pharmaceutically acceptable salt thereof, and tofacitinib, or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical combination comprising 1-(((2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl)methoxy)-7-methoxyisoquinoline-6-carboxamide, or a pharmaceutically acceptable salt thereof, tofacitinib, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, vehicle, or diluent, or a combination thereof.

3. A method of treating rheumatoid arthritis in a human comprising administering to the human in need of rheumatoid arthritis treatment a therapeutically effective amount of a pharmaceutical combination according to claim 1 .

4. A method of treating rheumatoid arthritis in a human comprising administering to the human in need of rheumatoid arthritis treatment a therapeutically effective amount of a pharmaceutical combination according to claim 2 .

5. A pharmaceutical combination comprising 1-(((2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl)methoxy)-7-methoxyisoquinoline-6-carboxamide, or a pharmaceutically acceptable salt thereof, and a JAK3 inhibitor, or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical combination comprising 1-(((2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl)methoxy)-7-methoxyisoquinoline-6-carboxamide, or a pharmaceutically acceptable salt thereof, a JAK3 inhibitor, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, vehicle, or diluent, or a combination thereof.

7. A method of treating rheumatoid arthritis in a human comprising administering to the human in need of rheumatoid arthritis treatment a therapeutically effective amount of the pharmaceutical combination according to claim 5 .

8. A method of treating rheumatoid arthritis in a human comprising administering to the human in need of rheumatoid arthritis treatment a therapeutically effective amount of the pharmaceutical combination according to claim 6 .

Assignees

• Pfizer

Inventors

• Trzupek John David
• Lee Katherine Lin
• Bunnage Mark Edward
• Han Seungil
• Hepworth David
• Lovering Frank Eldridge
• Mathias John Paul
• Papaioannou Nikolaos
• Pierce Betsy Susan
• Strohbach Joseph Walter
• Wright Stephen Wayne
• Zapf Christoph Wolfgang
• Gavrin Lori Krim
• Lee Arthur
• Anderson David Randolph
• Curran Kevin Joseph
• Dehnhardt Christoph Martin
• Saiah Eddine
• Goldberg Joel Adam
• Wang Xiaolun
• Huang Horng-Chih
• Vargas Richard
• Lowe Michael Dennis
• Patny Akshay

Classifications

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D217/22

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring · CPC title

• C07D215/48 Primary

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen · CPC title

• C07D207/273

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms · CPC title