Compositions and methods for inhibiting protein kinases

Patent metadata

Field	Value
Publication number	US-11135209-B2
Application number	US-201816496503-A
Country	US
Kind code	B2
Filing date	Mar 29, 2018
Priority date	Mar 29, 2017
Publication date	Oct 5, 2021
Grant date	Oct 5, 2021

Abstract

Identified compounds demonstrate protein kinase inhibitory activity and inhibition of dependent cell signaling pathways, such as NOD2 cell signaling. 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 1 is H,

R 2 is H, SO 2 Me, SO 2 i—Pr, SO 2 CF 3 , or

R 3 is H, Cl, Me, NH 2 , NHMe, NHSO 2 Me 3 , or NMe 2 ;
R 4 is H, F, Cl, OMe, OEt, O-n-Pr, O-i-Pr, OPh, or OCF 3 ;
R 5 is H, Me, Et, Pr, i-Pr, OMe, OEt, O-n-Pr, O-i-Pr, OCF 3 , Cl, or F;
R 6 is H, Me, or Et;
R 7 is Me, Et, n-Pr, i-Pr, CF 3 , CF 2 Et, CH 2 Ph, or Ph;
n is 0 or 1; and
wherein Me is methyl, Et is ethyl, i-Pr is isopropyl, and Ph is phenyl.

2. 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.

3. The compound demonstrating protein kinase inhibitory activity of claim 1 wherein the compound has a structure of:

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

5. A compound demonstrating NOD2 cellular signaling inhibitory activity and having a structure of:

wherein R 1 is H,

R 2 is H, SO 2 Me, SO 2 i-Pr, SO 2 CF 3 , or

R 3 is H, Cl, Me, NH 2 , NHMe, NHSO 2 Me 3 , or NMe 2 ;
R 4 is H, F, Cl, OMe, OEt, O-n-Pr, O-i-Pr, OPh, or OCF 3 ;
R 5 is H, Me, Et, Pr, i-Pr, OMe, OEt, O-n-Pr, O-i-Pr, OCF 3 , Cl, or F;
R 6 is H, Me, or Et;
R 7 is Me, Et, n-Pr, i-Pr, CF 3 , CF 2 Et, CH 2 Ph, or Ph;
n is 0 or 1; and
wherein Me is methyl, Et is ethyl, i-Pr is isopropyl, and Ph is phenyl.

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. The compound demonstrating NOD 2 cellular signaling inhibitory activity of claim 5 wherein the compound has a structure of:

8. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 7 and a pharmaceutically acceptable excipient, adjuvant, carrier, buffer, stabilizer, or mixture thereof.

Assignees

• Univ Houston System
• Tufts College

Inventors

• Cuny Gregory
• Suebsuwong Chalada
• Degterev Alexei

Classifications

• A61K31/444 Primary

  containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title

• A61K31/44 Primary

  Non condensed pyridines; Hydrogenated derivatives thereof · CPC title