Therapeutic uses of selected pyrazolopyrimidine compounds with anti-Mer tyrosine kinase activity

Patent metadata

Field	Value
Publication number	US-9555030-B2
Application number	US-201514678879-A
Country	US
Kind code	B2
Filing date	Apr 3, 2015
Priority date	Apr 11, 2014
Publication date	Jan 31, 2017
Grant date	Jan 31, 2017

Abstract

Pyrazolopyrimidine compounds, methods of use, and processes for making compounds with anti-Mer tyrosine kinase activity comprising Formula I, II, III, IV, or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof, are provided. The pyrazolopyrimidine compounds described herein have Mer tyrosine kinase (MerTK) inhibitory activity and are useful as anti-infective agents, immunostimulatory and immunomodulatory agents, anti-cancer agents (including against MerTK −/− tumors and ITD and TKD mutant forms of Acute Myeloid Leukemia (AML)), and as adjunctive agents in combination with chemotherapeutic, radiation or other standard of care for neoplasms.

First claim

The invention claimed is:

1. A method for treating a host with an infectious disease, comprising administering an effective amount of the following compound:

or a pharmaceutically acceptable salt, thereof.

2. The method of claim 1 , wherein the infectious disease is a viral infection.

3. The method of claim 1 , wherein the infectious disease is a bacterial infection.

4. The method of claim 2 , wherein the virus is selected from the group consisting of a Flavivirus, Hepacivirus, Pegivirus, Pestivirus, Filovirus, Togavirus, Coronavirus, Orthomyxovirus, Paramyxovirus, Calicivirus, and Lentivirus.

5. The method of claim 2 , wherein the virus is Chikungunya.

6. The method of claim 2 , wherein the virus is HCV.

7. The method of claim 2 , wherein the virus is HIV.

8. The method of claim 3 , wherein the bacterial disease is selected from the group consisting of Escherichia coli, Staphylococcus aureus, Enterococcus faecalis , and Streptococcus pneumoniae.

9. A method for treating a host with a medical disorder in need of immunostimulatory adjunctive therapy in combination with a direct acting drug for the medical disorder, comprising administering an adjunctively immunostimulatory effective amount of the following compound:

or a pharmaceutically acceptable composition or salt thereof.

Assignees

• Univ North Carolina Chapel Hill

Inventors

• Wang Xiaodong
• Frye Stephen

Classifications

• A61K31/5513

  1,4-Benzodiazepines, e.g. diazepam {or clozapine} · CPC title

• A61P43/00

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

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/505

  Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim · CPC title