Compounds and methods for kinase modulation, and indications therefor

Patent metadata

Field	Value
Publication number	US-2016168146-A1
Application number	US-201615048851-A
Country	US
Kind code	A1
Filing date	Feb 19, 2016
Priority date	Jul 17, 2007
Publication date	Jun 16, 2016
Grant date	—

Abstract

Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

First claim

1 - 20 . (canceled)

21 . A compound of formula (Ia):

or a pharmaceutically acceptable salt thereof,
wherein:
L 1 is a bond, —N(H)C(O)—, —N(H)—; —N(H)—S(O) 2 —, or —N(H)—C(NH)—;
each R 1 is optionally substituted lower alkyl or optionally substituted heteroaryl;
R 2 is hydrogen or halogen;
R 4 is hydrogen;
R 3 is optionally substituted lower alkyl or optionally substituted aryl;
m is 0, 1, 2, 3, 4, or 5; and
Ar is a monocyclic heteroaryl containing 5 to 6 atoms or a bicyclic heteroaryl containing 8 to 10 atoms wherein at least one atom is nitrogen,
with the proviso that Ar is other than

 wherein

 indicates the point of the attachment to L 1 .

22 . The compound of claim 21 , wherein R 2 is hydrogen.

23 . The compound of claim 21 , wherein R 2 is halogen.

24 . The compound of claim 21 , wherein R 3 is optionally substituted phenyl.

25 . The compound of claim 21 , wherein R 3 is phenyl substituted with one or more substituents selected from the group consisting of fluoro, lower alkyl, fluoro substituted lower alkyl, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, and fluoro substituted lower alkylthio.

26 . The compound of claim 21 , wherein R 3 is phenyl substituted with one or more fluoro.

27 . The compound of claim 21 , wherein each R 1 is optionally substituted lower alkyl.

28 . The compound of claim 21 , wherein each R 1 is optionally substituted heteroaryl.

29 . The compound of claim 21 , wherein Ar is a monocyclic heteroaryl containing 5 to 6 atoms.

30 . A pharmaceutical composition comprising a compound of claim 21 and a pharmaceutically acceptable carrier or excipient.

31 . A pharmaceutical composition comprising a compound of claim 21 and another therapeutic agent.

32 . A method for treating a subject suffering from melanoma, thyroid cancer or colorectal cancer, said method comprising administering to the subject an effective amount of a compound of claim 21 .

33 . The method of claim 32 , wherein the melanoma is melanoma having a mutation encoding a V600E amino acid substitution.

Assignees

• Plexxikon Inc

Inventors

• Wu Guoxian
• Zhang Jiazhong
• Zhu Yong-Liang
• Zhang Chao
• Ibrahim Prabha N
• Shi Songyuan
• Spevak Wayne
• Artis Dean R
• Tsai James

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title