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