Imidazopyrazine SYK inhibitors
Imidazopyrazines of Formula I and pharmaceutically acceptable salts and mixtures thereof, are provided herein. Pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle are also provided. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include cancer (e.g., B-cell lymphoma and leukemia), autoimmune diseases, inflammatory diseases, acute inflammatory reactions, and allergic disorders. Methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for determining the presence or absence of Syk kinase in a sample.
1. A compound chosen from
or a pharmaceutically acceptable salt thereof.
2. A pharmaceutical composition comprising a compound of claim 1 , together with at least one pharmaceutically acceptable vehicle chosen from carriers, adjuvants and excipients.
3. A method for inhibiting ATP hydrolysis, the method comprising contacting cells expressing Syk with a compound of claim 1 in an amount sufficient to detectably decrease the level of ATP hydrolysis in vitro.
4. The method of claim 3 wherein the cells are present in a mammal.
5. The method of claim 4 wherein the mammal is a human.
6. A method for determining the presence of Syk in a sample, comprising contacting the sample with a compound of claim 1 under conditions that permit detection of Syk activity, detecting a level of Syk activity in the sample, and therefrom determining the presence or absence of Syk in the sample.
7. A method for inhibiting B-cell activity comprising contacting cells expressing Syk with a compound of claim 1 , in an amount sufficient to detectably decrease B-cell activity in vitro.