5-bromo-indirubins

Patent metadata

Field	Value
Publication number	US-2021053919-A1
Application number	US-202016921856-A
Country	US
Kind code	A1
Filing date	Jul 6, 2020
Priority date	Mar 14, 2014
Publication date	Feb 25, 2021
Grant date	—

Abstract

Disclosed herein are compositions and methods for treating cancer, FLT3-AML, and CML.

First claim

1 . (canceled)

2 . The method of claim 43 , wherein R 50 is hydrogen or unsubstituted alkyl.

3 - 5 . (canceled)

6 . The method of claim 43 , wherein R 51 is hydrogen, oxo, halogen, —CF 3 , —CN, —OH, —NH 2 , —COH, —CH 2 COOH, —CONH 2 , —NO 2 , or unsubstituted alkyl.

7 .- 9 . (canceled)

10 . The method of claim 43 , wherein R 52 is halogen, —OH, —NH 2 , —COOH, —CONH 2 , or unsubstituted alkyl.

11 .- 24 . (canceled)

25 . A method of treating acute myeloid leukemia expressing a FLT3-kinase in a subject in need thereof, said method comprising administering an effective amount of a compound having the formula:

wherein,
L is a bond or substituted or unsubstituted alkylene;
R 1 is hydrogen, halogen, —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —OCF 3 , —OCCl 3 , —OCBr 3 , —OCI 3 , —CN, —OH, —NH 2 , —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;
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 hydrogen, 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, —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —OCF 3 , —OCCl 3 , —OCBr 3 , —OCI 3 , —CN, —OH, —NH 2 , —C(O)OH, —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;
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,
including pharmaceutically acceptable salts thereof,
thereby treating said acute myeloid leukemia.

26 .- 29 . (canceled)

30 . The method of claim 25 , wherein R 1 is halogen, —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —OCF 3 , —OCCl 3 , —OCBr 3 , —OCI 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.

31 . (canceled)

32 . The method of claim 25 , 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.

33 .- 42 . (canceled)

43 . A method of treating acute myeloid leukemia expressing a FLT3-kinase in a subject in need thereof, said method comprising administering an effective amount of a compound having formula

wherein
R 50 is hydrogen, oxo, halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CH 2 COOH, —CONH 2 , —NO 2 , —SH, —OCF 3 , —OCHF 2 , or unsubstituted alkyl;
R 51 is hydrogen, oxo, halogen, —CF 3 , —CN, —OH, —NR 51A R 51B , —COOH, —CH 2 COOH, —CONH 2 , —NO 2 , —SH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, or unsubstituted heteroalkyl;
R 51A and R 51B are independently hydrogen or unsubstituted alkyl;
R 52 is halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , or unsubstituted alkyl; and
z1 and z2 are independently 0, 1, 2, 3, 4, or 5,

including pharmaceutically acceptable salts thereof; and
thereby treating said acute myeloid leukemia.

44 .- 45 . (canceled)

46 . The method of claim 25 or 43 , wherein said FLT3-kinase is a FLT3-mutant kinase.

47 . The method of claim 46 , wherein said FLT3-mutant kinase is a FLT3-TKD mutant kinase.

48 . The method of claim 47 , wherein said FLT3-TKD mutant kinase comprises a mutation at an amino acid residue position corresponding to D835, 1836, D839, S840, N841, or Y842 of SEQ ID NO: 1.

49 . The method of claim 46 , wherein said FLT3-mutant kinase comprises a FLT3-ITD mutant kinase.

50 .- 53 . (canceled)

54 . A method of modulating activity of a FLT3-kinase, said method comprising contacting a FLT3-kinase with a compound having formula:

wherein,
L is a bond or substituted or unsubstituted alkylene;
R 1 is hydrogen, halogen, —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —OCF 3 , —OCCl 3 , —OCBr 3 , —OCI 3 , —CN, —OH, —NH 2 , —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;
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 hydrogen, 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, —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —OCF 3 , —OCCl 3 , —OCBr 3 , —OCI 3 , —CN, —OH, —NH 2 , —C(O)OH, —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 unsu

Assignees

• Hope City

Inventors

• Nam Sangkil
• Horne David
• Xie Jun

Classifications

• C07D209/40 Primary

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