2,3-disubstituted pyrido[3,4-b]pyrazine-containing compounds as kinase inhibitors

Patent metadata

Field	Value
Publication number	US-2023219934-A1
Application number	US-202118009311-A
Country	US
Kind code	A1
Filing date	Jun 24, 2021
Priority date	Jun 24, 2020
Publication date	Jul 13, 2023
Grant date	—

Abstract

The present invention generally relates to 2,3-Disubstituted pyrido[3,4-b]pyrazine-containing compounds as a kinase inhibitor and methods of uses thereof. Pharmaceutical compositions and methods for treating those kinase related diseases are within the scope of this invention.

First claim

1 . A compound of generic structure of

or a pharmaceutically acceptable salt thereof,
wherein R 1 is methyl, ethyl, or —CF 3 ;
R 2 and R 3 are, independently, hydrogen, an amino, alkylamino, heteroalkylamino, alkylheteroalkylamino, dialkylamino, diheteroalkylamino, alkoxy, heteroalkoxy, or an acylamido (—NH—COR 4 , wherein R 4 is an alkyl or an heteroalkyl); and
W is an amide, a sulfonamide, or a urea.

2 . The compound according to claim 1 , wherein said compound has a formula (II),

or a pharmaceutically acceptable salt thereof,
wherein R 1 is methyl, ethyl, or —CF 3 ;
R 2 and R 3 are, independently, hydrogen, an amino, alkylamino, heteroalkylamino, alkylheteroalkylamino, dialkylamino, diheteroalkylamino, alkoxy, heteroalkoxy, or an acylamido (—NH—COR 4 , wherein R 4 is an alkyl or an heteroalkyl); and
R is an alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, acyl, aryl, heteroaryl, arylalkyl, arylalkenyl, or arylalkynyl, each of which is optionally substituted.

3 . The compound according to claim 1 , wherein said compound has a formula (III),

or a pharmaceutically acceptable salt thereof,
wherein R 1 is methyl, ethyl, or —CF 3 ;
R 2 and R 3 are, independently, hydrogen, an amino, alkylamino, heteroalkylamino, alkylheteroalkylamino, dialkylamino, diheteroalkylamino, alkoxy, heteroalkoxy, or an acylamido (—NH—COR 4 , wherein R 4 is an alkyl or an heteroalkyl); and
R is an alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocyclyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, acyl, aryl, heteroaryl, arylalkyl, arylalkenyl, or arylalkynyl, each of which is optionally substituted.

4 . The compound according to claim 1 , wherein said compound has a formula (IV),

or a pharmaceutically acceptable salt thereof,
wherein R 1 is methyl, ethyl, or —CF 3 ;
R 2 and R 3 are, independently, hydrogen, an amino, alkylamino, heteroalkylamino, alkylheteroalkylamino, dialkylamino, diheteroalkylamino, alkoxy, heteroalkoxy, or an acylamido (—NH—COR 4 , wherein R 4 is an alkyl or an heteroalkyl); and
R is an 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 of claim 1 , wherein R 1 is methyl; and R 2 and R 3 are hydrogen.

6 . The compound of claim 1 , wherein R 1 is methyl; R 2 is amino; and R 3 is hydrogen.

7 . The compound of claim 1 , wherein R 1 is methyl; R 3 is amino; and R 2 is hydrogen.

8 . The compound of claim 1 , wherein R 1 is ethyl; R 3 is amino; and R 2 is hydrogen.

9 . The compound of claim 1 , wherein R 1 is methoxy; R 3 is amino; and R 2 is hydrogen.

10 . The compound of claim 1 , wherein R 1 is methoxy; and R 2 and R 3 are hydrogen.

11 . The compound of claim 1 , wherein R 1 is ethyl; R 2 and R 3 are hydrogen.

12 . The compound of claim 1 , wherein R 1 is ethyl; R 2 is amino; and R 3 is hydrogen.

13 . The compound of claim 1 , wherein said compound has a formula of:

14 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, N-oxide,
hydrate, solvent, tautomer, or optical isomer thereof, and a pharmaceutically acceptable carrier or diluent.

15 . A method of ameliorating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of

Assignees

• Purdue Research Foundation

Inventors

• Sintim Herman O
• Larocque Elizabeth Anne
• Hernandez Delmis E
• Dayal Neetu

Classifications

• C07D491/147 Primary

  the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom · CPC title

• C07D403/14 Primary

  containing three or more hetero rings · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title