Inhibitors of protein kinases
View Patent ↗Provided are methods of treating inflammatory disorders, autoimmune disorders, or a hematological malignancies using compounds of formula I and pharmaceutically acceptable tautomers, salts, or stereoisomers thereof. Such disorders and conditions include leukemia and Non Hodgkin's Lymphoma.
1. A method for treating a leukemia comprising the step of administering to a subject in need of such treatment a therapeutically effective amount of a compound having the formula I
or a pharmaceutically acceptable salt thereof, wherein:
D 1 is cyclopropyl;
R 1 is selected from the group consisting of H, C 1-8 alkyl, amino, aminocarbonyl, hydroxyl, C 1-8 alkoxy, C 1-8 haloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, oxo, cyano, C 1-8 alkoxycarbonyl, C 3-8 cycloalkyl, aryl and heterocyclyl; and each heterocyclyl is optionally substituted with from 1 to 4 substituents selected from the group consisting of C 1-8 alkyl, halo, oxo, amino, C 1-8 alkoxy, C 1-8 alkylcarbonyl, arylC 1-8 alkoxycarbonyl, aminocarbonyl, arylC 1-8 alkylenecarbonyl and C 1-8 alkylsulfonyl
Y 1 is phenyl optionally substituted with from 1 to 3 R 4a substituents, independently selected from the group consisting of C 1-8 alkyl, C 1-8 alkoxyC 1-8 alkyl, aminocarbonyl-, hydroxyl, halogen, hydroxy, C 1-8 alkoxy and C 1-8 alkylsulfonyl;
R 2 is piperazinyl;
and wherein R 2 is further substituted with from 1 to 2 R 4c substituents, independently selected from the group consisting of C 1-8 alkylcarbonyl and C 1-8 alkylsulfonyl.
2. The method of claim 1 , wherein said leukemia is selected from the group consisting of acute myeloid leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, B-cell prolymphocytic leukemia, hairy cell leukemia, T-cell prolymphocytic leukemia, T-cell granular lymphocytic leukemia, and aggressive NK-cell leukemia.
3. The method of claim 2 , wherein said leukemia is acute myeloid leukemia.
4. The method of claim 2 , wherein said leukemia is chronic lymphocytic leukemia.
5. The method of claim 2 , wherein said leukemia is acute lymphoblastic leukemia.
6. The method of claim 2 , wherein said leukemia is chronic myelogenous leukemia.
7. The method of claim 1 , wherein the compound of formula I is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
8. The method of claim 1 , wherein the compound of formula I has the formula
or a pharmaceutically acceptable salt thereof.
9. The method of claim 3 , wherein the compound of formula I has the formula
or a pharmaceutically acceptable salt thereof.
10. The method of claim 4 , wherein the compound of formula I has the formula
or a pharmaceutically acceptable salt thereof.
11. The method of claim 5 , wherein the compound of formula I has the formula
or a pharmaceutically acceptable salt thereof.
12. The method of claim 6 , wherein the compound of formula I has the formula
or a pharmaceutically acceptable salt thereof.