Oxysterols and hedgehog signaling

Abstract

Described herein are compounds and pharmaceutical compositions containing such compounds which inhibit Hedgehog signaling. Also described herein are methods for using such Hedgehog signaling inhibitors, alone or in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of Hedgehog signaling.

What is claimed is: 
     
         1 . A method of treating cancer in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, having the structure: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkenyl, substituted or unsubstituted C 1 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted -C 1 -C 4 alkylaryl; 
 R 6  is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl; 
    is a single or double bond; 
 R 2 , R 3 , R 4 , and R 5  are independently hydrogen, deuterium, or —OH; 
 R 7  is hydrogen, substituted or unsubstituted C 1 -C 8 alkyl, or —C(O)NR 8 R 9 ; and 
 R 8  and R 9  are independently hydrogen, substituted or unsubstituted C 1 -C 8 alkyl, or substituted or unsubstituted aryl. 
 
     
     
         2 . The method of  claim 1 , wherein R 1  is substituted or unsubstituted C 1 -C 8 alkyl or substituted or unsubstituted phenyl. 
     
     
         3 . The method of  claim 2 , wherein R 1  is substituted or unsubstituted C 1 -C 8 alkyl. 
     
     
         4 . The method of  claim 3 , wherein R 1  is —CF 3 . 
     
     
         5 . The method of  claim 3 , wherein R 1  is —CH 3 . 
     
     
         6 . The method of  claim 1 , wherein R 6  is substituted or unsubstituted phenyl. 
     
     
         7 . The method of  claim 6 , wherein R 6  is substituted phenyl. 
     
     
         8 . The method of  claim 7 , wherein R 6  is 4-fluorophenyl. 
     
     
         9 . The method of  claim 1 , wherein R 2 , R 3 , R 4 , and R 5  are each hydrogen. 
     
     
         10 . The method of  claim 1 , wherein R 7  is hydrogen or substituted or unsubstituted C 1 -C 8 alkyl. 
     
     
         11 . The method of  claim 10 , wherein R 7  is —CH 3 . 
     
     
         12 . The method of  claim 10 , wherein R 7  is hydrogen. 
     
     
         13 . The method of  claim 1 , wherein   is a single bond. 
     
     
         14 . The method of  claim 1 , wherein   is a double bond. 
     
     
         15 . The method of  claim 1 , wherein the compound of Formula (I) is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         16 . The method of  claim 1 , wherein the cancer is selected from basal cell carcinoma, melanoma, leukemia, multiple myeloma, stomach cancer, pancreatic cancer, bladder cancer, prostate cancer, ovarian cancer, bone cancer, brain cancer, lung cancer, breast cancer, liver cancer, colon cancer, rhabdomycosarcoma, and skin cancer. 
     
     
         17 . The method of  claim 1 , wherein the compound is administered orally, intravenously, intraperitoneally, subcutaneously, or as an aerosol. 
     
     
         18 . The method of  claim 1  further comprising the administration of a second therapeutic agent. 
     
     
         19 . The method of  claim 18 , wherein the second therapeutic agent is an anti-tumor agent. 
     
     
         20 . The method of  claim 19 , wherein the anti-tumor agent is an oxysterol, a Hedgehog pathway antagonist, a chemotherapeutic agent, or a combination thereof.