5-bromo-indirubins

Patent metadata

Field	Value
Publication number	US-2020283421-A1
Application number	US-202016790611-A
Country	US
Kind code	A1
Filing date	Feb 13, 2020
Priority date	Mar 14, 2013
Publication date	Sep 10, 2020
Grant date	—

Abstract

Disclosed herein inter alia are compositions and methods for treating cancer using 5-Br-indirubin derivatives.

First claim

1 . A compound, or pharmaceutically acceptable salt thereof, having the formula:

wherein
L is a bond or substituted or unsubstituted alkylene;
R 1 is hydrogen, halogen, —CX 1 3 , —OCX 1 3 , —CN, —OH, —NH 2 , —COOH, —C(O)OR 4 , —CONH 2 , —NO 2 , —SH, —NHNH 2 , —NR 2 R 3 , —OR 4 , —SR 4 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;

X l is independently a halogen;
R 2 and R 3 are independently substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, wherein R 2 and R 3 are optionally joined together to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
R 4 is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 5 and R 6 are independently hydrogen, halogen, —CX 2 3 , —OCX 2 3 , —CN, —OH, —NH 2 , —COOH, —C(O)OR 9 , —CONH 2 , —NO 2 , —SH, —NHNH 2 , —NR 7 R 8 , —OR 9 , —SR 9 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
X 2 is independently a halogen;
R 7 and R 8 are independently substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, wherein R 7 and R 8 are optionally joined together to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; and
R 9 is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

2 . The compound of claim 1 , wherein R 5 and R 6 are hydrogen.

3 .- 5 . (canceled)

6 . The compound of claim 1 , wherein L is unsubstituted C 2 alkylene or a bond.

7 .- 8 . (canceled)

9 . The compound of claim 1 , wherein R 1 is —NR 2 R 3 .

10 .- 15 . (canceled)

16 . The compound of claim 1 , wherein R 2 and R 3 are joined together to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl.

17 . (canceled)

18 . The compound of claim 1 , wherein R 2 and R 3 are joined together to form a substituted or unsubstituted C 5 -C 7 heterocycloalkyl.

19 .- 21 . (canceled)

22 . The compound of claim 16 , wherein R 2 and R 3 are joined together to form a substituted or unsubstituted pyrrolidinyl or substituted or unsubstituted piperazinyl.

23 . (canceled)

24 . The compound of claim 1 comprising a protonated nitrogen cation or a plurality of protonated nitrogen cations.

25 . (canceled)

26 . The compound of claim 1 having formula:

or a pharmaceutically acceptable salts thereof.

27 . The compound of claim 1 having formula:

or a pharmaceutically acceptable salts thereof.

28 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 .

29 . The compound of claim 1 for use in treating cancer in a subject in need thereof.

30 . The compound of claim 29 , wherein said compound is administered in an effective amount to said subject.

31 . The compound of claim 29 , wherein said compound is in a pharmaceutical composition comprising a pharmaceutically acceptable excipient.

32 . The compound of claim 29 , wherein said cancer is lung cancer, breast cancer, ovarian cancer, leukemia, lymphoma, melanoma, pancreatic cancer, sarcoma, bladder cancer, bone cancer, brain cancer, cervical cancer, colon cancer, esophageal cancer, gastric cancer, liver cancer, head and neck cancer, kidney cancer, myeloma, thyroid cancer, or prostate cancer.

33 . The compound of claim 29 , wherein said compound is co-administered with an effective amount of an anti-cancer agent.

34 . A method of modulating, a JAK, JAK2, TYK2, Src, c-Src, ABL1, ABL1 T315I, an Aurora kinase, Aurora A, GSK-3b, a CDK, a STAT, or STAT3, said method comprising contacting the protein with the compound of claim 1 .

35 . The method of claim 34 , wherein the compound is in a pharmaceutical composition comprising a pharmaceutically acceptable excipient.

36 . A method of modulating a Janus kinase, said method comprising contacting said Janus kinase with the compound of claim 1 .

37 . The method of claim 36 , wherein the compound is in a pharmaceutical composition comprising a pharmaceutically acceptable excipient.

Assignees

• Hope City
• National And Kapodistrian Univ Of Athens

Inventors

• Jove Richard
• Nam Sangkil
• Horne David
• Xie Jun
• Skaltsounis Alexios Leandros
• Kritsanida Marina
• Gaboriaud-Kolar Nicolas

Classifications

• C07D401/14

  containing three or more hetero rings · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• C07D209/48

  with oxygen atoms in positions 1 and 3, e.g. phthalimide · CPC title

• A61K31/404 Primary

  Indoles, e.g. pindolol · CPC title

• C07D403/14 Primary

  containing three or more hetero rings · CPC title