Pyrido[3,2-d]pyrimidine compounds uses thereof for treating a proliferative disease

Patent metadata

Field	Value
Publication number	US-12139488-B2
Application number	US-202418628424-A
Country	US
Kind code	B2
Filing date	Apr 5, 2024
Priority date	Apr 19, 2021
Publication date	Nov 12, 2024
Grant date	Nov 12, 2024

Abstract

Compounds, compositions and their use in the treatment of a proliferative disease or condition such as a said proliferative disease or disorder is associated with a RAF gene mutation and/or a RAS gene mutation. The compounds disclosed are of Formula I or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, X1, X2, X3 and X4 are as defined herein:

First claim

The invention claimed is:

1. A compound of formula:

or a pharmaceutically acceptable salt thereof, wherein:

2. The compound of claim 1 , wherein the compound is a pharmaceutically acceptable salt of:

3. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.

9. A method of treating a subject suffering from a proliferative disease or disorder, comprising administering to the subject a compound of formula:

or a pharmaceutically acceptable salt thereof,
wherein:

wherein the proliferative disease or disorder is selected from a group consisting of: melanoma, thyroid carcinoma, colorectal, ovarian cancer, breast cancer, endometrial cancer, liver cancer, sarcoma, stomach cancer, pancreatic carcinoma, Barret's adenocarcinoma, glioma, lung cancer, head and neck cancer, acute lymphoblastic leukemia, acute myelogenous leukemia, non-Hodgkin's lymphoma, and hairy-cell leukemia.

10. The method of claim 9 , wherein the compound is a pharmaceutically acceptable salt of:

11. The method of claim 9 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

12. The method of claim 9 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

13. The method of claim 9 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

14. The method of claim 9 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

15. The method of claim 9 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

16. A method of treating a subject suffering from a melanoma, comprising administering to the subject a compound of formula:

or a pharmaceutically acceptable salt thereof, wherein:

17. The method of claim 16 , wherein the compound is a pharmaceutically acceptable salt of:

18. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

19. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

20. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

21. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

22. The method of claim 16 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

Assignees

• Univ Montreal

Inventors

• Beaulieu Pierre Louis
• Dore Michael

Classifications

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• C07D519/00 Primary

  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

• C07F9/6561

  containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• A61K31/541

  Non-condensed thiazines containing further heterocyclic rings · CPC title