THERAPEUTIC USES OF SELECTED PYRAZOLOPYRIMIDINE COMPOUNDS WITH ANTI-MER TYROSINE KINASE ACTIVITY

摘要

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.

主权项

1. A method for treating a host with an infectious disease, comprising administering an effective amount of a compound of the formula: wherein:
R1 is aryl such as phenyl optionally substituted 1, 2 or 3 times with heterocycloalkylalkyl, which heterocycloalkylalkyl is substituted or unsubstituted; heterocycloalkylalkyl is a substituent of the formula —R′R″;
R′ is substituted or unsubstituted C1-C2 alkyl, andR″ is a heterocyclo group, such as an optionally substituted piperazine or morpholine group;R2 is —R5R6, where R5 is a covalent bond or C1 to C3 alkyl and R6 is cycloalkyl, heterocycloalkyl, aryl, heteroaryl or alkyl, and wherein R6 is optionally substituted from one to two times with independently selected polar groups;R3 is —NR7R8, where R7 and R8 are each independently selected from H, alkyl, arylalkyl; and alkoxyalkyl; andR4 is H, loweralkyl, halo, or loweralkoxy; or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof.