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