Methods for Treating Cancer Using Pyrimidine and Pyridine Compounds with BTK Inhibitory Activity

Abstract

The present invention provides methods of treating cancer using pyrimidine and pyridine compounds which are inhibitors of Bruton's tyrosine kinase (BTK).

What is claimed is: 
     
         1 : A method of treating acute myeloid leukemia in a human subject, comprising:
 administering a therapeutically effective amount of a compound of the formula 1-(4-(((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)-4-fluoropiperidin-1-yl)prop-2-en-1-one or a pharmaceutically acceptable salt thereof to the human subject.   
     
     
         2 : The method of  claim 1 , wherein the compound of the formula 1-(4-(((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)-4-fluoropiperidin-1-yl)prop-2-en-1-one is administered to the human subject. 
     
     
         3 : The method of  claim 1 , wherein the pharmaceutically acceptable salt of the compound of the formula 1-(4-(((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)-4-fluoropiperidin-1-yl)prop-2-en-1-one is administered to the human subject. 
     
     
         4 : The method of  claim 1 , wherein the compound or the pharmaceutically acceptable salt thereof is administered to the human subject orally. 
     
     
         5 : The method of  claim 1 , wherein the compound of the formula 1-(4-(((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)-4-fluoropiperidin-1-yl)prop-2-en-1-one or the pharmaceutically acceptable salt thereof is administered as a pharmaceutical composition comprising the compound and at least one pharmaceutical carrier. 
     
     
         6 : The method of  claim 5 , wherein the pharmaceutical composition comprises about 20 mg to about 100 mg of the compound. 
     
     
         7 : The method of  claim 6 , wherein the pharmaceutical composition comprises 20 mg of the compound. 
     
     
         8 : The method of  claim 6 , wherein the pharmaceutical composition comprises 50 mg of the compound. 
     
     
         9 : The method of  claim 6 , wherein the pharmaceutical composition comprises 80 mg of the compound. 
     
     
         10 : The method of  claim 6 , wherein the pharmaceutical composition comprises 100 mg of the compound. 
     
     
         11 : The method of  claim 5 , wherein the pharmaceutical composition comprises about 160 mg of the compound. 
     
     
         12 : The method of  claim 5 , wherein the pharmaceutical composition comprises about 600 mg of the compound. 
     
     
         13 : The method of  claim 5 , wherein the pharmaceutical composition comprises about 900 mg of the compound. 
     
     
         14 : The method of  claim 5 , wherein the pharmaceutical composition is a capsule containing the compound. 
     
     
         15 : The method of  claim 5 , wherein the pharmaceutical composition is administered to the human subject orally. 
     
     
         16 : The method of  claim 5 , wherein the pharmaceutical composition is administered twice daily. 
     
     
         17 : The method of  claim 1 , wherein the therapeutically effective amount eliminates is an amount that eliminates binding to off-target polypeptides. 
     
     
         18 : The method of  claim 1 , wherein about 7.5 mg/kg of the compound is administered orally once per day. 
     
     
         19 : The method of  claim 1 , wherein about 25 mg/kg of the compound is administered orally once per day. 
     
     
         20 : The method of  claim 1 , wherein the treatment achieves a normal level of cell proliferation.