Methods and compositions associated with the granulocyte colony-stimulating factor receptor

Patent metadata

Field	Value
Publication number	US-10736875-B2
Application number	US-201816126199-A
Country	US
Kind code	B2
Filing date	Sep 10, 2018
Priority date	Nov 14, 2011
Publication date	Aug 11, 2020
Grant date	Aug 11, 2020

Abstract

Some embodiments include compositions and methods of using or identifying compounds that modulate the activity of the granulocyte colony-stimulating factor receptor (GCFR). Some embodiments include use of compounds to treat certain disorders, such as hematopoietic or neurological disorders.

First claim

What is claimed is:

1. A method of treating a disorder selected from the group consisting of granulocytopenia, neutropenia, amyotrophic lateral sclerosis, multiple sclerosis, multiple dystrophy, and spinal cord injury, the method comprising administering an effective amount of a compound to a subject in need thereof, wherein the compound has the structure of Formula (IV):

a tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:
R 4 is a 3,5-dimethyl phenyl;
R 5 is CF 3 ;
R 9 is selected from an optionally substituted C 1 -C 6 alkyl, and a C 2 -C 6 alkenyl substituted with —COOH or halogen;
W is NH;
X is N (nitrogen);
Y is C 4 alkenyl.

2. The method of claim 1 , wherein R 9 is an optionally substituted C 1 -C 6 alkyl.

3. The method of claim 2 , wherein R 9 is an optionally substituted C 1 -C 3 alkyl.

4. The method of claim 3 , wherein R 9 is C 1 -C 3 alkyl.

5. The method of claim 1 , wherein the disorder is selected from the group consisting of granulocytopenia, neutropenia, amyotrophic lateral sclerosis, multiple sclerosis, and multiple dystrophy.

6. The method of claim 1 , wherein the compound is administered in combination with an additional therapeutic regimen selected from the group consisting of chemotherapy, bone marrow transplantation, and radiation therapy.

7. The method of claim 1 having the structure:

a tautomer thereof, or pharmaceutically acceptable salt thereof.

8. The method of claim 1 , wherein the compound is:

9. The method of claim 1 , wherein R 9 is C 2 -C 6 alkenyl substituted with —COOH.

10. The method of claim 1 , wherein R 9 is C 2 -C 6 alkenyl substituted with halogen.

11. The method of claim 1 , wherein the disorder is granulocytopenia.

12. The method of claim 1 , wherein the disorder is neutropenia.

13. The method of claim 1 , wherein the disorder is amyotrophic lateral sclerosis.

14. The method of claim 1 , wherein the disorder is multiple sclerosis.

15. The method of claim 1 , wherein the disorder is multiple dystrophy.

16. The method of claim 1 , wherein the disorder is a spinal cord injury.

Assignees

• Ligand Pharm Inc

Inventors

• Zhi Lin
• Marschke Keith
• Grant Virginia H
• Roach Steven L
• Shen Yixing
• Pickens Jason C
• Pedram Bijan
• Van Oeveren Cornelis Arjan
• Valdez Lino J
• Hudson Andrew R

Classifications

• C07D209/34 Primary

  in position 2 · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/404 Primary

  Indoles, e.g. pindolol · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• C07D231/52

  Oxygen atom in position 3 and nitrogen atom in position 5, or vice versa · CPC title