5-bromo-indirubins

Patent metadata

Field	Value
Publication number	US-2018170915-A1
Application number	US-201815898151-A
Country	US
Kind code	A1
Filing date	Feb 15, 2018
Priority date	Mar 14, 2013
Publication date	Jun 21, 2018
Grant date	—

Abstract

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

First claim

What is claimed is:

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 1 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 . The compound of claim 1 , wherein L is unsubstituted alkylene.

4 . The compound of claim 1 , wherein L is unsubstituted C 1 -C 8 alkylene.

5 . The compound of claim 1 , wherein L is unsubstituted C 1 -C 4 alkylene.

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

7 . The compound of claim 1 , wherein L is a bond.

8 . The compound of claim 1 , wherein R 1 is halogen, —CX 3 , —OCX 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.

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

10 . The compound of claim 9 , wherein 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.

11 . The compound of claim 10 , wherein R 2 and R 3 are independently substituted or unsubstituted alkyl.

12 . The compound of claim 11 , wherein R 2 and R 3 are independently substituted or unsubstituted C 1 -C 8 alkyl.

13 . The compound of claim 12 , wherein R 2 and R 3 are independently substituted or unsubstituted C 1 -C 4 alkyl.

14 . The compound of claim 13 , wherein R 2 and R 3 are independently —OH substituted or unsubstituted C 1 -C 4 alkyl.

15 . The compound of claim 13 , wherein R 2 and R 3 are independently unsubstituted C 1 -C 4 alkyl.

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

18 . The compound of claim 17 , wherein R 2 and R 3 are joined together to form a substituted or unsubstituted C 5 -C 7 heterocycloalkyl.

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

20 . The compound of claim 19 , wherein R 2 and R 3 are joined together to form an R 23 -substituted C 5 -C 7 heterocycloalkyl, wherein R 23 is independently a substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl.

21 . The compound of claim 20 , wherein R 23 is independently a substituted or unsubstituted C 1 -C 8 alkyl or substituted or unsubstituted 2 to 8 membered heteroalkyl.

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

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

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

25 . The compound of claim 1 comprising a plurality of protonated nitrogen cations.

26 . The compound of claim 1 having formula:

including pharmaceutical salts thereof.

27 . The compound of claim 1 having formula:

including pharmaceutical 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.

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

• 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

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07D209/40

  Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone · CPC title