6-arylamino pyridone carboxamide as MEK inhibitors

Patent metadata

Field	Value
Publication number	US-9540396-B2
Application number	US-201113996233-A
Country	US
Kind code	B2
Filing date	Nov 1, 2011
Priority date	Nov 2, 2010
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

Abstract

The invention provides novel substituted 6-arylamino pyridone carboxamides represented by Formula I, or a pharmaceutically acceptable salt, solvate, poly-morph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of MEK and are useful in the treatment of inflammatory diseases, cancer and other hyperproliferative diseases. The invention further provides a method of treatment for inflammatory diseases, cancer and other hyperproliferative diseases in mammals, especially humans.

First claim

What is claimed is:

1. A compound of formula I

wherein
represents X—Y═W or W—Y═X,
X independently represent N, O, or S;
W is CR 2 , N, or S;
Y is N or CR 1 ; and
R 1 is selected from the group consisting of H and C 1 -C 6 alkyl; wherein each alkyl is optionally substituted with 1-3 substituents selected independently from the group consisting of halogen, hydroxy, amino, C 1 -C 6 alkylamino, diC 1 -C 6 alkylamino, and C 1 -C 6 heterocyclyl;
R 2 is selected from the group consisting of H and C 1 -C 10 alkyl, where each alkyl is unsubstituted or substituted with 1-3 substituents selected independently from halogen, hydroxyl, and C 1 -C 4 alkyl;
R 3 is selected from the group consisting of H, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, C 3 -C 10 cycloalkyl, C 3 -C 10 cycloalkylalkyl, where each alkyl, alkoxy, and cycloalkyl is unsubstituted or substituted with 1-3 substituents selected independently from the group consisting of halogen, hydroxyl, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;
R 3′ is selected from the group consisting of H and C 1 -C 6 alkyl;
R 4 , R 5 , R 6 , R 7 and R 8 are independently selected from the group consisting of H, halogen, SR 9 , and OR 9 ;
R 9 is selected from the group consisting of hydrogen and C 1 -C 10 alkyl;
R 13 is selected from the groups consisting of H and C 1 -C 6 alkyl; and
R 14 is selected from the groups consisting of H and C 1 -C 6 alkyl;
or a pharmaceutically acceptable salt, solvate, poly-morph, or tautomer thereof.

2. The compound according to claim 1 , wherein Y is CR 1 .

3. The compound according to claim 1 , wherein represents X—Y═W; X is O or S; Y is CR 1 ; and W is CR 2 .

4. The compound according to claim 1 , wherein R 3 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxyl and C 1 -C 4 alkoxy; C 1 -C 6 alkoxyl optionally substituted with one or more substituents selected from the group consisting of halogen and hydroxyl; C 3 -C 6 cycloalkyl optionally substituted with C 1 -C 4 alkyl.

5. The compound according to claim 4 , wherein R 3 is selected from the group consisting of C 1 -C 6 alkyl and C 1 -C 6 alkoxy, where alkyl and alkoxy are independently unsubstituted or substituted with one or more substituents selected independently from the group consisting of halogen and hydroxyl.

6. The compound according to claim 1 , wherein R 4 , R 5 , R 6 , R 7 and R 8 are independently selected from H or halogen.

7. The compound according to claim 6 , wherein one of R 4 and R 8 is fluorine or chlorine, and R 6 is iodine.

8. The compound according to claim 7 which is selected from the following

9. A pharmaceutical composition comprising a pharmaceutically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.

10. A method for the treatment of a MEK mediated disorder or disease in a subject comprising administration of the compound of claim 1 , wherein the MEK mediated disorder or disease is melanoma.

Assignees

• Xiao Dengming
• Zhu Li
• Hu Yuandong
• Wang Shixin
• Yu Rong
• Hu Wei
• Liang Zhi
• Liu Xijie
• Hu Quan
• Centaurus Biopharma Co Ltd
• Chia Tai Tianqing Pharmaceutical Group Co Ltd

Inventors

• Xiao Dengming
• Zhu Li
• Hu Yuandong
• Wang Shixin
• Yu Rong
• Hu Wei
• Liang Zhi
• Liu Xijie
• Hu Quan

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D498/04

  Ortho-condensed systems · CPC title

• A61K31/4545

  containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine · CPC title

• A61P29/00

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