Histone demethylase inhibitors

Abstract

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted amidopyridine or amidopyridazine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

1 - 50 . (canceled) 
     
     
         51 . A method of inhibiting a histone demethylase enzyme comprising contacting the enzyme with a compound of Formula (XI), or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein: 
         Q is —CO 2 R, —C(O)N(H)CN, —C(O)N(H)OH, or tetrazolyl; 
         R is hydrogen or optionally substituted alkyl; 
         G is —X—Y: 
         X is —C 1  alkylene: 
         Y is optionally substituted tetralinyl, optionally substituted chromanyl, optionally substituted tetrahydroquinolinyl, optionally substituted benzofuranyl, optionally substituted 2,3-dihydrobenzofuranyl, optionally substituted 2,3-dihydrobenzo[b] [1,4]dioxinyl, optionally substituted naphthyl, optionally substituted indolyl, optionally substituted 1,2-dihydronaphthyl, optionally substituted indanyl, or optionally substituted thiochromanyl. 
       
     
     
         52 . (canceled) 
     
     
         53 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein R is hydrogen. 
     
     
         54 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein R is optionally substituted alkyl. 
     
     
         55 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein Y is optionally substituted tetralinyl. 
     
     
         56 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein Y is optionally substituted chromanyl. 
     
     
         57 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein Y is optionally substituted tetrahydroquinolinyl. 
     
     
         58 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein Y is optionally substituted benzofuranyl. 
     
     
         59 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein Y is optionally substituted 2,3-dihydrobenzofuranyl. 
     
     
         60 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein Y is optionally substituted naphthyl. 
     
     
         61 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein Y is optionally substituted indolyl. 
     
     
         62 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein Y is optionally substituted 1,2-dihydronaphthyl. 
     
     
         63 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein Y is optionally substituted indanyl. 
     
     
         64 . The compound or pharmaceutically acceptable salt of  claim 51 , wherein Y is optionally substituted thiochromanyl. 
     
     
         65 . The compound or pharmaceutically acceptable salt of  claim 55 , wherein the optionally substituted tetralinyl is an optionally substituted 1-tetralinyl. 
     
     
         66 . The compound or pharmaceutically acceptable salt of  claim 65 , wherein the compound of Formula (XI) has the structure: 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  is hydrogen, methyl, or —OH; 
         each R 4  is independently hydrogen, fluoro, or methyl; and 
         R 5 , R 6 , R 7  and R 8  are each independently chosen from hydrogen, halogen, —OH, —CN, optionally substituted C 1 -C 6  alkyl, optionally substituted C 1 -C 6  alkoxy, optionally substituted C 3 -C 7  carbocyclyl, optionally substituted C 3 -C 7  carbocyclyloxy, optionally substituted C 4 -C 12  carbocyclylalkyl, optionally substituted C 4 -C 12  carbocyclylalkoxy, optionally substituted C 1 -C 6  alkynyl, optionally substituted C 1 -C 6  alkenyl, optionally substituted C 6 -C 10  aryl, optionally substituted C 6 -C 10  aryloxy, optionally substituted C 6 -C 10  aryl-S—, optionally substituted C 7 -C 14  aralkoxy, optionally substituted heteroaryl, and optionally substituted heteroaryloxy. 
       
     
     
         67 . The compound or pharmaceutically acceptable salt of  claim 66 , wherein R 1  is hydrogen. 
     
     
         68 . The compound or pharmaceutically acceptable salt of  claim 66 , wherein each R 4  is hydrogen. 
     
     
         69 . The compound or pharmaceutically acceptable salt of  claim 66  wherein R 5  is hydrogen. 
     
     
         70 . The compound or pharmaceutically acceptable salt of  claim 66 , wherein R 6  is hydrogen. 
     
     
         71 . The compound or pharmaceutically acceptable salt of  claim 66 , wherein R 7  is hydrogen. 
     
     
         72 . The compound or pharmaceutically acceptable salt of  claim 66 , wherein R 8  is hydrogen. 
     
     
         73 . The compound or pharmaceutically acceptable salt of  claim 66 , wherein R 6  is not hydrogen. 
     
     
         74 . The compound or pharmaceutically acceptable salt of  claim 66 , wherein R 6  is chosen from optionally substituted C 1 -C 6  alkyl, optionally substituted C 1 -C 6  alkoxy, optionally substituted C 3 -C 7  carbocyclyl, optionally substituted C 3 -C 7  carbocyclyloxy, optionally substituted C 4 -C 12  carbocyclylalkyl, optionally substituted C 4 -C 12  carbocyclylalkoxy, optionally substituted C 1 -C 6  alkynyl, optionally substituted C 1 -C 6  alkenyl, optionally substituted C 6 -C 10  aryl, optionally substituted C 6 -C 10  aryloxy, optionally substituted C 6 -C 10  aryl-S—, optionally substituted C 7 -C 14  aralkoxy, optionally substituted heteroaryl, and optionally substituted heteroaryloxy.