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

Patent metadata

Field	Value
Publication number	US-9649309-B2
Application number	US-201514678898-A
Country	US
Kind code	B2
Filing date	Apr 3, 2015
Priority date	Apr 11, 2014
Publication date	May 16, 2017
Grant date	May 16, 2017

Abstract

Uses of pyrimidines with anti-Mer tyrosine kinase activity 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 a compound having the following structure:

or a pharmaceutically acceptable salt thereof, wherein the infectious disease is a viral infection caused by a virus selected from the group consisting of a Flavivirus, Hepacivirus, Pegivirus, Pestivirus, Filovirus, Togavirus, Coronavirus, Orthomyxovirus, Paramyxovirus, Calicivirus, and Lentivirus.

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

or a pharmaceutically acceptable salt thereof, wherein the infectious disease is a bacterial disease.

3. The method of claim 1 , wherein the virus is Chikungunya.

4. The method of claim 1 , wherein the virus is HCV.

5. The method of claim 1 , wherein the virus is HIV.

6. The method of claim 2 , wherein the bacterial disease is selected from the group consisting of Escherichia coli, Staphylococcus aureus, Enterococcus faecalis , and Streptococcus pneumoniae.

7. 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 a compound having the following structure:

or a pharmaceutically acceptable salt thereof.

8. 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 where the medical disorder is acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) comprising administering an adjunctively immunostimulatory effective amount of a compound having the following structure:

or a pharmaceutically acceptable salt thereof.

9. The method of claim 8 , wherein the AML or ALL is resistant to prior drug therapy.

10. The method of claim 8 , wherein the AML contains a mutation within the FLT3-TKD at amino acid F691 or D835.

Assignees

• Univ North Carolina Chapel Hill

Inventors

• Wang Xiaodong
• Zhang Weihe
• Frye Stephen

Classifications

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61K45/06

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

• A61K31/5513

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

• C07D487/04

  Ortho-condensed systems · CPC title

• A61K31/506 Primary

  not condensed and containing further heterocyclic rings · CPC title