Pyrido[2,3-d]pyrimidin-7-ones and related compounds as inhibitors of protein kinases

Patent metadata

Field	Value
Publication number	US-12012402-B2
Application number	US-202117499995-A
Country	US
Kind code	B2
Filing date	Oct 13, 2021
Priority date	May 15, 2017
Publication date	Jun 18, 2024
Grant date	Jun 18, 2024

Abstract

Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2). Compounds that are either dual RIPK2/ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 could provide therapeutic benefit.

First claim

What is claimed is:

1. A compound demonstrating protein kinase inhibitory activity and having a structure of:

wherein R is SO 2 Me at any one available ring position, or wherein R is

at any one available ring position other than ring position four, wherein Me is methyl and Et is ethyl;
A is CH and D is CH;
E is N, CH, or C—R;
B and C are independently N, CH, or C—Cl;
R 1 is H, or R 1 is Cl, F, OCH 3 , C(CH 3 ) 3 , or OH at one available ring position; and
X-Y is

wherein R 2 is H, alkyl, hydroxyalkyl, alkoxyalkyl, or arylalkyl, wherein when R is

B and C are independently N or CH, and R 1 is F, C(CH 3 ) 3 , or OH at one available ring position.

2. The compound of claim 1 , wherein R 2 is methyl, ethyl, isobutyl, 2-hydroxyethyl, 2-methoxyethyl, benzyl, or phenethyl.

3. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutically acceptable excipient, adjuvant, carrier, buffer, stabilizer, or mixture thereof.

4. A method of treating a protein kinase related disease or condition, wherein the condition is inflammatory bowel disease or multiple sclerosis, comprising administering the pharmaceutical composition of claim 3 .

5. A compound demonstrating protein kinase inhibitory activity, wherein the compound has a structure of:

6. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 5 and a pharmaceutically acceptable excipient, adjuvant, carrier, buffer, stabilizer, or mixture thereof.

7. A method of treating a protein kinase related disease or condition, wherein the condition is inflammatory bowel disease or multiple sclerosis, comprising administering the pharmaceutical composition of claim 6 .

8. A compound demonstrating protein kinase inhibitory activity and having a structure of:

wherein R is H,

SO 2 Me, or

wherein Me is methyl and Et is ethyl;
R 1 is any alkyl or aryl group;
A is CH and D is N or CH;
E is N, CH, or C—R;
B and C are independently N, CH, or C—Cl;
R 3 is H, or R 3 is Cl, F, OCH 3 , C(CH 3 ) 3 , or OH at one available ring position; and
X-Y are

wherein R 2 is H, alkyl, hydroxyalkyl, alkoxyalkyl, or arylalkyl.

9. The compound of claim 8 , wherein R 1 is methyl, ethyl, or propyl.

10. The compound of claim 8 , wherein R 2 is methyl, ethyl, isobutyl, 2-hydroxyethyl, 2-methoxyethyl, benzyl, or phenethyl.

11. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 8 and a pharmaceutically acceptable excipient, adjuvant, carrier, buffer, stabilizer, or mixture thereof.

12. A method of treating a protein kinase related disease or condition, wherein the condition is inflammatory bowel disease or multiple sclerosis, comprising administering the pharmaceutical composition of claim 11 .

Assignees

• Univ Houston System
• Tufts College

Inventors

• Cuny Gregory
• Nikhar Sameer
• Degterev Alexei

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title