Inhibitors of kinase networks and uses thereof

Patent metadata

Field	Value
Publication number	US-11891391-B2
Application number	US-202117243629-A
Country	US
Kind code	B2
Filing date	Apr 29, 2021
Priority date	Mar 29, 2017
Publication date	Feb 6, 2024
Grant date	Feb 6, 2024

Abstract

The present invention generally relates to compounds as a dual kinase-demethylase inhibitor useful for the treatment of diseases mediated by a kinase and/or a histone demethylase, such as inflammation, cancer, viral and bacterial infections, neurological and immunological disorders. Pharmaceutical compositions and methods for treating those diseases are within the scope of this invention.

First claim

The invention claimed is:

1. A compound having a formula

or a pharmaceutically acceptable salt thereof, wherein n is 3-5; the bonding between A and B and bonding between B and D can be a single bond or a double bond, but both bonds between A and B and between B and D cannot be a double bond at the same time; A, B, and D each represent, independently, C, O, N, or S, wherein at least one of A, B, and D is a heteroatom;
R 1 is amino, hydroxyl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, acyl, aryl, heteroaryl, arylalkyl, arylalkenyl, or arylalkynyl, each of which is optionally substituted;
R 4 represents two substituents, each independently selected from the group consisting of hydrogen, deuterium, halo, azido, cyano, nitro, hydroxy, amino, thio, carboxy, ester, amide, acyl, sulfoxyl, sulfonyl, phosphate, phosphoryl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, arylalkenyl, and arylalkynyl, each of which is optionally substituted;
or the two substituents are taken together with the attached carbons to form an optionally substituted cyclic or heterocyclic moiety;
depending on A, B, and D, R 5 represents two or three substituents, each independently selected from the group consisting of hydrogen, deuterium, halo, azido, cyano, nitro, hydroxy, amino, thio, carboxy, ester, amide, acyl, sulfoxyl, sulfonyl, phosphate, phosphoryl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, arylalkenyl, and arylalkynyl, each of which is optionally substituted; and
depending on the value of n, R 6 represents four to six substituents, each independently selected from the group consisting of hydrogen, deuterium, halo, azido, cyano, nitro, hydroxy, amino, thio, carboxy, ester, amide, acyl, sulfoxyl, sulfonyl, phosphate, phosphoryl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, arylalkenyl, and arylalkynyl, each of which is optionally substituted.

2. The compound according to claim 1 ,
wherein R 1 is

3. A compound having a formula

or a pharmaceutically acceptable salt thereof, wherein n is 3; the bonding between A and B and bonding between B and D can be a single bond or a double bond, but both bonds between A and B and between B and D cannot be a double bond at the same time; A, B, and D each represent, independently, C, O, N, or S, wherein at least one of A, B, and D is a heteroatom;
R 1 is heterocyclyl or heteroaryl either of which is optionally substituted;
R 4 represents two substituents, each independently selected from the group consisting of hydrogen, deuterium, halo, azido, cyano, nitro, hydroxy, amino, thio, carboxy, ester, amide, acyl, sulfoxyl, sulfonyl, phosphate, phosphoryl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, arylalkenyl, and arylalkynyl, each of which is optionally substituted;
or the two substituents are taken together with the attached carbons to form an optionally substituted cyclic or heterocyclic moiety;
depending on A, B, and D, R 5 represents two or three substituents, each independently selected from the group consisting of hydrogen, deuterium, halo, azido, cyano, nitro, hydroxy, amino, thio, carboxy, ester, amide, acyl, sulfoxyl, sulfonyl, phosphate, phosphoryl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, arylalkenyl, and arylalkynyl, each of which is optionally substituted; and
R 6 represents four substituents, each independently selected from the group consisting of hydrogen, deuterium, halo, azido, cyano, nitro, hydroxy, amino, thio, carboxy, ester, amide, acyl, sulfoxyl, sulfonyl, phosphate, phosphoryl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, arylalkenyl, and arylalkynyl, each of which is optionally substituted.

4. The compound according to claim 1 , wherein
the bond between A and B is a double bond, wherein each A and B represents, independently, CR 8 , N, or NR 9 , wherein R 8 and R 9 represent independently hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, acyl, aryl, heteroaryl, arylalkyl, arylalkenyl, or arylalkynyl, each of which is optionally substituted;
depending on A and B, R 5 represents one or two substituents, each independently selected from the group consisting of hydrogen, deuterium, halo, azido, cyano, nitro, hydroxy, amino, thio, carboxy, ester, amide, acyl, sulfoxyl, sulfonyl, phosphate, phosphoryl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, arylalkenyl, and arylalkynyl, each of which is optionally substituted; and
D is N—R 7 , wherein R 7 is a hydrogen alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, acyl, aryl, heteroaryl, arylalkyl, arylalkenyl, or arylalkynyl, each of which is optionally substituted.

5. The compound according to claim 4 , wherein R 1 is

6. The compound according to claim 4 , wherein R 1 is

A is carbon (C); B is nitrogen (N); and R 5 , R 6 , and R 7 all represent hydrogen.

7. The compound according to claim 3 , wherein the compound is

8. A pharmaceutical composition comprising:
a compound of claim 7 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent, excipient, or carrier.

Assignees

• Purdue Research Foundation

Inventors

• Sintim Herman O
• Dayal Neetu
• Opoku-Temeng Clement

Classifications

• C07D471/14 Primary

  Ortho-condensed systems · CPC title

• C07D209/08

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring · CPC title

• C07D231/56

  Benzopyrazoles; Hydrogenated benzopyrazoles · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title