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

Patent metadata

Field	Value
Publication number	US-10111859-B2
Application number	US-201615247164-A
Country	US
Kind code	B2
Filing date	Aug 25, 2016
Priority date	Nov 14, 2011
Publication date	Oct 30, 2018
Grant date	Oct 30, 2018

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 hematopoietic or neurological 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 of Formula (II) wherein the compound of Formula (II) has the following structure:

a tautomer thereof, or a pharmaceutically acceptable salt thereof,
wherein:
R 3 is selected from hydrogen, an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 2 -C 6 alkenyl, an optionally substituted C 2 -C 6 alkynyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted C 3 -C 8 cycloalkyl, an optionally substituted C 3 -C 8 cycloalkenyl, an optionally substituted C 1 -C 6 heterocycle, an optionally substituted aryl, and an optionally substituted heteroaryl;
R 4 is selected from hydrogen, an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 2 -C 6 alkenyl, an optionally substituted C 2 -C 6 alkynyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted C 3 -C 8 cycloalkyl, an optionally substituted C 3 -C 8 cycloalkenyl, an optionally substituted C 1 -C 6 heterocycle, an optionally substituted heteroaryl, and an optionally substituted heteroarylalkyl;
R 9 is selected from hydrogen, an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 2 -C 6 alkenyl, an optionally substituted C 2 -C 6 alkynyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted C 3 -C 8 cycloalkyl, an optionally substituted C 3 -C 8 cycloalkenyl, an optionally substituted C 1 -C 6 heterocycle, an optionally substituted heteroaryl, an optionally substituted arylalkyl, an optionally substituted arylalkenyl, an optionally substituted arylalkynyl, an optionally substituted heteroarylalkyl, an optionally substituted heteroarylalkenyl, and an optionally substituted heteroarylalkynyl;
W is selected from O (oxygen) and NH;
X is N (nitrogen) or CR 2 ; and
Y is selected from an optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted C 1 -C 6 heteroalkenyl, an optionally substituted phenylalkenyl, and an optionally substituted heterocyclealkenyl.

2. The method of claim 1 , wherein the compound has the structure of Formula (IIa) or (IIb):

a tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:
R 3 is selected from hydrogen, an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 3 -C 8 cycloalkyl, an optionally substituted C 1 -C 6 heterocycle, an optionally substituted aryl, and an optionally substituted heteroaryl;
R 4 is selected from an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 3 -C 8 cycloalkyl, an optionally substituted C 1 -C 6 heterocyclyl; and
R 9 is selected from hydrogen, an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 3 -C 8 cycloalkyl, an optionally substituted C 1 -C 6 heterocyclyl, an optionally substituted heteroaryl, an optionally substituted arylalkyl, and an optionally substituted heteroarylalkyl.

3. The method of claim 2 , wherein:
R 3 is selected from hydrogen, and an optionally substituted C 1 -C 3 alkyl;
R 4 is selected from an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 3 -C 8 cycloalkyl; and
R 9 is selected from an optionally substituted C 1 -C 6 alkyl, an optionally substituted arylalkyl, an optionally substituted arylalkenyl, an optionally substituted arylalkynyl, and an optionally substituted heteroarylalkyl.

4. The method of claim 3 , wherein:
R 3 is an optionally substituted C 1 -C 3 alkyl;
R 4 is an optionally substituted C 1 -C 4 alkyl; and
R 9 is selected from an optionally substituted C 1 -C 3 alkyl, an optionally substituted arylalkyl, an optionally substituted arylalkenyl, and an optionally substituted arylalkynyl.

5. 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.

6. The method of claim 1 , wherein the compound is selected from the group consisting of:

a tautomer thereof, or pharmaceutically acceptable salt thereof.

7. A method of treating a hematopoietic or neurological 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, wherein the compound is selected from the group consisting:

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

Assignees

• Ligand Pharm Inc

Inventors

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

Classifications

• A61P7/06

  Antianaemics · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title