Compounds For Repressing Cancer Cell Growth

Abstract

The disclosure generally relates to compounds, compositions, and methods for the treatment of cancer by restoring the P53 pathway signaling to repress cancer cell growth.

1 - 22 . (canceled) 
     
     
         23 . A compound of Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is hydrogen or a substituted or unsubstituted haloalkyl group; 
 each R 2 , R 3 , R 4 , R 5 , R 6 , and R 7  is, independently, hydrogen, halogen, hydroxyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted phosphate, substituted or unsubstituted phosphoramidate, substituted or unsubstituted amine, substituted or unsubstituted alkylamino, substituted or unsubstituted acylamino, substituted or unsubstituted aminoalkoxy, or substituted or unsubstituted alkylthio; or 
 a compound of Formula II: 
 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is hydrogen or a substituted or unsubstituted alkyl group; 
 each R 2 , R 3 , R 4 , R 5 , R 6 , and R 7  is, independently, hydrogen, halogen, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, or substituted or unsubstituted amine; 
 X is sulfur, oxygen, or —NH; and 
 n is an integer from 0 to 5; or 
 a compound of Formula III: 
 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 1  and R 2  are, independently, hydrogen or a substituted or unsubstituted alkyl; 
 R 3  is a substituted or unsubstituted heteroaryl; and 
 n is an integer from 0 to 5. 
 
     
     
         24 . A method of treating a cancer in a mammal comprising administering to the mammal in need thereof a compound of Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is hydrogen or a substituted or unsubstituted haloalkyl group; 
 each R 2 , R 3 , R 4 , R 5 , R 6 , and R 7  is, independently, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted phosphate, substituted or unsubstituted phosphoramidate, substituted or unsubstituted amine, substituted or unsubstituted alkylamino, substituted or unsubstituted acylamino, substituted or unsubstituted aminoalkoxy, or substituted or unsubstituted alkylthio. 
 
     
     
         25 . The method of  claim 24 , wherein the cancer is a tumor suppressor protein p53 mutated associated cancer, tumor suppressor protein Rb mutated associated cancer, tumor suppressor protein NF1 mutated associated cancer, tumor suppressor protein p16 mutated associated cancer, tumor suppressor protein p27 mutated associated cancer, or tumor suppressor protein VHL mutated associated cancer. 
     
     
         26 . The method of  claim 24 , wherein the human is also administered radiation therapy, a chemotherapeutic agent, an immunotherapeutic agent, a lysosome inhibitor, or a calpain inhibitor, or any combination thereof. 
     
     
         27 . A method of treating a cancer in a mammal comprising administering to the mammal in need thereof a compound of Formula II: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is hydrogen or a substituted or unsubstituted alkyl group; 
 each R 2 , R 3 , R 4 , R 5 , R 6 , and R 7  is, independently, hydrogen, halogen, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, or substituted or unsubstituted amine; 
 X is sulfur, oxygen, or —NH; and 
 n is an integer from 0 to 5. 
 
     
     
         28 . The method of  claim 27 , wherein R 1  is hydrogen or an unsubstituted alkyl. 
     
     
         29 . The method of  claim 27 , wherein each R 2 , R 3 , R 4 , R 5 , R 6 , and R 7  is, independently, hydrogen, halogen, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, or substituted or unsubstituted amine. 
     
     
         30 . The method of  claim 27 , wherein X is sulfur or oxygen. 
     
     
         31 . The method of  claim 27 , wherein n is an integer from 0 to 3. 
     
     
         32 . The method of  claim 27 , wherein: R 1  is hydrogen or an unsubstituted alkyl; each R 2 , R 3 , R 4 , R 5 , R 6 , and R 7  is, independently, hydrogen, halogen, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, or substituted or unsubstituted amine; X is sulfur or oxygen; and n is an integer from 0 to 3. 
     
     
         33 . The method of  claim 27 , wherein the cancer is a tumor suppressor protein p53 mutated associated cancer, tumor suppressor protein Rb mutated associated cancer, tumor suppressor protein NF1 mutated associated cancer, tumor suppressor protein p16 mutated associated cancer, tumor suppressor protein p27 mutated associated cancer, or tumor suppressor protein VHL mutated associated cancer. 
     
     
         34 . The method of  claim 27 , wherein the human is also administered radiation therapy, a chemotherapeutic agent, an immunotherapeutic agent, a lysosome inhibitor, or a calpain inhibitor, or any combination thereof. 
     
     
         35 . A method of treating a cancer in a mammal comprising administering to the mammal in need thereof a compound of Formula III: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 1  and R 2  are, independently, hydrogen or a substituted or unsubstituted alkyl; 
 R 3  is a substituted or unsubstituted heteroaryl; and 
 n is an integer from 0 to 5. 
 
     
     
         36 . The method of  claim 35 , wherein R 1  and R 2  are, independently, hydrogen or an unsubstituted alkyl. 
     
     
         37 . The method of  claim 35 , wherein n is an integer from 0 to 3. 
     
     
         38 . The method of  claim 35 , wherein R 3  is an unsubstituted heteroaryl. 
     
     
         39 . The method of  claim 35 , wherein: R 1  and R 2  are, independently, hydrogen or an unsubstituted alkyl; n is an integer from 0 to 3; and R 3  is an unsubstituted heteroaryl. 
     
     
         40 . The method of  claim 35 , wherein the cancer is a tumor suppressor protein p53 mutated associated cancer, tumor suppressor protein Rb mutated associated cancer, tumor suppressor protein NF1 mutated associated cancer, tumor suppressor protein p16 mutated associated cancer, tumor suppressor protein p27 mutated associated cancer, or tumor suppressor protein VHL mutated associated cancer. 
     
     
         41 . The method of  claim 35 , wherein the human is also administered radiation therapy, a chemotherapeutic agent, an immunotherapeutic agent, a lysosome inhibitor, or a calpain inhibitor, or any combination thereof.