Pyridinone and pyridazinone derivatives

Patent metadata

Field	Value
Publication number	US-9561231-B2
Application number	US-201313796437-A
Country	US
Kind code	B2
Filing date	Mar 12, 2013
Priority date	Jun 12, 2012
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

Abstract

The present invention provides for compounds of formula (I)

wherein A 1 , A 2 , A 3 , A 4 , J, and X 3 have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, diabetes, obesity, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula I.

First claim

The invention claimed is:

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof:

Wherein J is a group of formula IIa or IIb:

wherein
R 1a is C 1 -C 3 alkyl, C 2 -C 3 alkylene-OH, or C 1 -C 3 haloalkyl;
Y 1a is N or CR xa , wherein R xa is H, halo, C 1 -C 3 alkyl, —O—C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —O—C 1 -C 3 haloalkyl, aryl, aryl-C 1 -C 3 alkylene-OH, aryl-C 1 -C 3 alkylene-heterocycloalkyl, C(O)NR 10 R 12 , wherein heterocycloalkyl of aryl-C 1 -C 3 alkylene-heterocycloalkyl may be substituted with one to three C 1 -C 3 alkyl,
R 1b is H, C 1 -C 3 alkyl, C 2 -C 3 alkylene-OH, or C 1 -C 3 haloalkyl;
Y 1b is N or CR xb , wherein R xb is heteroaryl, H, halo, C 1 -C 3 alkyl, —O—C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —O—C 1 -C 3 haloalkyl, aryl, aryl-C 1 -C 3 alkylene-OH, aryl-C 1 -C 3 alkylene-heterocycloalkyl, C(O)NR 10 R 12 , wherein heterocycloalkyl of aryl-C 1 -C 3 alkylene-heterocycloalkyl may be substituted with one to three C 1 -C 3 alkyl; wherein said heteroaryl may be substituted with one to three groups selected from the group consisting of: C 1 -C 6 alkyl, C 1 -C 3 alkylene-aryl, C 1 -C 3 alkylene-heteroaryl, C 1 -C 3 alkylene-heterocycloalkyl, COOH, and COO—C 1 -C 4 alkyl,
X 2a is selected from the group consisting of: H, —NR 10 R 12 , halo, OH, —O—C 1 -C 4 alkyl, aryl, heteroaryl, —NR 10 C(O)—C 1 -C 4 alkyl, NR 10 C(O)O—C 1 -C 6 alkyl, and NR 10 S(O) 2 —C 1 -C 6 alkyl;
X 2b is C 1 -C 3 alkyl, C 2 -C 3 alkylene-OH, or C 1 -C 3 haloalkyl;
X 1a and X 1b are each selected from the group consisting of: hydrogen, halo, C 1 -C 6 alkyl, C 1 -C 4 haloalkyl, C 2 -C 4 alkenyl, —C 2 -C 4 alkenylene-O—C 1 -C 6 alkyl, C 2 -C 4 alkynyl, —C 2 -C 4 alkynylene-N(C 1 -C 6 alkyl) 2 , —O—C 1 -C 6 alkyl, —O—CD 2 CH 3 , —O—CD 2 CD 3 , —O—C 3 -C 7 cycloalkyl, —O-heterocycloalkyl, —O-aryl, —O—C 1 -C 3 alkylene-C 3 -C 7 cycloalkyl, —O—C 1 -C 3 alkylene-heterocycloalkyl, —O—C 1 -C 3 alkylene-aryl, wherein the aryl groups of the —O-aryl and —O—C 1 -C 3 alkylene-aryl, the C 3 -C 7 cycloalkyl groups of the —O—C 3 -C 7 cycloalkyl and —O—C 1 -C 3 alkylene-C 3 -C 7 cycloalkyl, and the heterocycloalkyl groups of the —O-heterocycloalkyl and —O—C 1 -C 3 alkylene-heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of oxo, halo, —CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, NH 2 , N(H)(alkyl), N(alkyl) 2 , —C(O)OC 1 -C 6 alkyl, and —C 1 -C 3 alkylene-heterocycloalkyl, —O—C 1 -C 4 haloalkyl, OH, —O—C 1 -C 6 alkylene-OH, —O—C 1 -C 6 alkylene-N(R 10 ) 2 , —O—C 1 -C 3 alkylene-C(O)O—C 1 -C 4 alkyl, —NR 10 —C 1 -C 6 alkyl, —NR 10 —C 1 -C 6 haloalkyl, —NR 10 —C(O)OC 1 -C 6 alkyl, —NR 10 —C(O)OC 1 -C 6 haloalkyl, —NR 10 —C(O)NR 10 R 12 , —NR 10 —SO 2 R 12 , —NR 10 —C 3 -C 7 cycloalkyl, —NR 10 —C 1 -C 3 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-OH, —C 1 -C 3 alkylene-C(O)OC 1 -C 4 alkyl, C 1 -C 3 alkylene-NR 10 C(O)—C 1 -C 4 alkyl, —C 1 -C 3 alkylene-C(O)NR 10 R 12 , —C 2 -C 4 alkenylene-C(O)—O—C 1 -C 4 alkyl, —C(O)—C 1 -C 4 alkyl, C(O)O—C 1 -C 4 alkyl, C(O)NR 10 R 12 , —NR 10 C(O)—C 1 -C 4 alkyl, —NR 10 —C 1 -C 3 alkylene-C(O)—C 1 -C 4 alkyl, —NR 10 —C 1 -C 3 alkylene-C(O)O—C 1 -C 4 alkyl, —SO 2 NR 10 R 12 , and any of groups i-v:
i) C 3 -C 14 cycloalkyl, which is optionally substituted with 1 to 3 of R 2 , where R 2 is selected from the group consisting of: halo, oxo, CN, —O—C 1 -C 4 alkyl, —O—C 1 -C 4 haloalkyl, —NR 10 R 12 , C(O)NR 10 R 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C(O)—C 1 -C 4 alkyl, —C(O)O—C 1 -C 4 alkyl, SO 2 NR 10 R 12 , SO 2 —C 1 -C 4 alkyl, and aryl, wherein said aryl is optionally substituted with 1 to 3 substituents independently selected from group consisting of: halo, C 1 -C 3 alkyl, C(O)—C 1 -C 3 alkyl, C(O)OH, C(O)NR 10 R 12 , and heteroaryl;
ii) heterocycloalkenyl, which is optionally substituted with 1 to 3 of R 2 , where R 2 is selected from the group consisting of: halo, oxo, CN, —O—C 1 -C 4 alkyl, —O—C 1 -C 4 haloalkyl, —NR 10 R 12 , C(O)NR 10 R 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C(O)—C 1 -C 4 alkyl, —C(O)O—C 1 -C 4 alkyl, SO 2 NR 10 R 12 , SO 2 —C 1 -C 4 alkyl, and aryl, wherein said aryl is optionally substituted with 1 to 3 substituents independently selected from group consisting of: halo, C 1 -C 3 alkyl, C(O)—C 1 -C 3 alkyl, C(O)OH, C(O)NR 10 R 12 , and heteroaryl;
iii) heterocycloalkyl, which is optionally substituted with 1 to 3 of R 3 , where R 3 is selected from the group consisting of: halo, oxo, CN, —O—C 1 -C 4 alkyl, —O—C 1 -C 4 haloalkyl, —NR 10 R 12 , C(O)NR 10 R 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C(O)—C 1 -C 4 alkyl, —C(O)O—C 1 -C 4 alkyl, SO 2 NR 10 R 12 , SO 2 —C 1 -C 4 alkyl, and aryl, wherein said aryl is optionally substituted with 1 to 3 substituents independently selected from group consisting of: halo, C 1 -C 3 alkyl, C(O)—C 1 -C 3 alkyl, C(O)OH, C(O)NR 10 R 12 , and heteroaryl;
iv) heteroaryl, which is optionally substituted with 1 to 3 of R 4 , where R 4 is selected from the group consisting of: halo, oxo, CN, —O—C 1 -C 4 alkyl, —O—C 1 -C 4 haloalkyl, —NR 10 R 12 , —C(O)H, C(O)NR 10 R 12 , C 1 -C 6 alkyl, C 1 -C 4 haloalkyl, C 1 -C 6 alkylene-heterocycloalkyl, C 1 -C 6 alkylene-aryl, C 1 -C 6 alkylene-heteroaryl, C(O)—C 1 -C 4 alkyl, —C(O)O—C 1 -C 4 alkyl, SO 2 NR 10 R 12 , SO 2 —C 1 -C 4 alkyl, —NR 14 C(O)C 1 -C 4 -alkyl, heterocycloalkyl, and aryl, wherein said aryl is optionally substituted with 1 to 3 substituents independently selected from group consisting of: halo, C 1 -C 3 alkyl, C(O)—C 1 -C 3 alkyl, C(O)OH, C(O)NR 10 R 12 , and heteroaryl,
wherein said heterocycloalkyl or heterocycloalkyl group of C 1 -C 6 alkylene-heterocycloalkyl is optionally substituted with 1 to 3 independently selected C 1 -C 3 alkyl groups, and wherein said heteroaryl group of C 1 -C 6 alkylene-heteroaryl and said aryl groups of C 1 -C 6 alkylene-aryl is optionally substituted with substituents 1 to 3 groups independently selected from C 1 -C 3 alkyl and NR 14 R 16 ;
v) aryl, which is optionally substituted with 1 to 3 of R 6 , where R 6 is selected from the group consisting of: halo, CN, —NR 14 R 16 , —N(R 14 )C(O)—C 1 -C 4 alkyl, —NR 14 SO 2 —C 1 -C 4 alkyl, C(O)H, C(O)C 1 -C 6 alkyl, C(O)heterocycloalkyl, C(O)NR 14 R 16 , —C 1 -C 4 alkylene-NR 14 R 16 , SO 2 NR 14 R 16 , C(O)OC 1 -C 4 alkyl, —SO 2 — heterocycloalkyl, —SO 2 —C 1 -C 6 alkyl, —C 1 -C 6 alkyl, —OH, —O—C 1 -C 6 alkyl, —C 1 -C 6 haloalkyl, —O—C 1 -C 6 haloalkyl, —C 1 -C 6 alkylene-OH, —C(H)(OH)(C 3 -C 7 cycloalkyl), —C(H)(OH)(phenyl), C 2 -C 4 alkenylene-OH, —C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, —C 1 -C 6 alkylene-OC(O)—C 1 -C 6 alkyl, —C 1 -C 6 alkylene-C(O)O—C 1 -C 6 alkyl, —C 1 -C 6 alkylene-N(H)SO 2 —C 1 -C 6 alkyl, —C 1 -C 6 alkylene-N(H)C(O)—C 1 -C 6 alkyl, —C 1 -C 6 alkylene-CN, —C 1 -C 6 alkylene-heterocycloalkyl, C 1 -C 6 alkylene-aryl, C 1 -C 6 alkylene-heteroaryl, heteroaryl, and heterocycloalkyl,
wherein said heterocycloalkyl and said heterocycloalkyl of said C(O)heterocycloalkyl and said C 1 -C 6 alkylene-heterocycloalkyl is optionally substituted with 1 to 3 groups independently selected from the group consisting of C 1 -C 6 alkyl, and C 1 -C 4 alkylene-aryl,
wherein said heteroaryl and the heteroaryl of said C 1 -C 6 alkylene-heteroaryl, and the aryl of said C 1 -C 6 alkylene-aryl is optionally substituted with 1 to 3 groups independently selected from the group consisting of C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, halo, —C 1 -C 3 alkylene-CN, —C 1 -C 3 alkylene-OH, —C 1 -C 3 alkylene-C(O)O—C 1 -C 3 alkyl, —C 1 -C 3 alkylene-O—C 1 -

Assignees

• Abbvie Inc

Inventors

• Hubbard Robert D
• Wang Le
• Park Chang H
• Sun Chaohong
• Mcdaniel Keith F
• Pratt John K
• Soltwedel Todd N
• Wendt Michael D
• Holms James H
• Liu Dachun
• Sheppard George S

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title