Novel HSP90 Inhibitor

Abstract

Disclosed is a triazole derivative(s) represented by the general formula (1) below or a pharmacologically acceptable salt(s) thereof. Also disclosed are a prodrug(s) of such a triazole derivative(s) and an HSP90 inhibitor(s) containing any one of them as an active constituent. (1) (In the formula, X represents a halogen atom, an optionally substituted alkyl group, an optionally substituted alkynyl group or the like; Y represents a mercapto group, a hydroxyl group, an optionally substituted sulfonyl group, an optionally substituted amino group or the like; and R represents an optionally substituted aryl or alkyl group or the like.)

1 . A method of inhibiting Hsp90 in a cell comprising:
 administering to the cell an effective amount of a compound of formula (I):   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, or a prodrug thereof, wherein: 
         R is an optionally substituted heterocyclic aryl or an optionally substituted carbocyclic aryl group; 
         R 1  and R 2  are —H, an acyl group, a carbamoyl group, an alkoxycarbonyl group, or an alkoxymethyl group; 
         X is an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, cyano group, halogen atom, nitro group, an optionally substituted cyclic alkyl group, an optionally substituted carbocyclic aryl group, an optionally substituted heterocyclic aryl group, hydroxyl group, an optionally substituted alkoxyl group, an optionally substituted aryloxy group, mercapto group, an optionally substituted alkylthio group, an optionally substituted arylthio group, an optionally substituted amino group, an optionally substituted carbamoyloxy group, an optionally substituted ureido group, an optionally substituted acyloxy group, an optionally substituted acylamino group, an optionally substituted alkoxycarbonyloxy group, an optionally substituted alkoxycarbonylamino group, an optionally substituted sulfonylamino group, an optionally substituted sulfamoylamino group, an optionally substituted acyl group, an optionally substituted carboxyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted carbamoyl group, an optionally substituted sulfamoyl group, an optionally substituted alkylsulfonyl group, an optionally substituted arylsulfonyl group, an optionally substituted alkylsulfinyl group, or an optionally substituted arylsulfinyl group; and 
         Y is —OH, —SH, an optionally substituted acyloxy group, an optionally substituted alkoxycarbonyloxy group, or an optionally substituted carbamoyloxy group; provided that when Y is —OH or —SH at least one of R 1  and R 2  is not hydrogen. 
       
     
     
         2 . The method of  claim 1 , wherein the compound is not
 3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-trifluoromethyl-phenyl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-methyl-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(8-methoxy-quinolin-5-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-hydroxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-ethyl-phenyl)-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-chloro-phenyl]-4-(quinolin-5-yl)-5-mercapto-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(2,3-difluoro-phenyl)-5-mercapto-[1,2,4]triazole; or   3-[2-Hydroxy-4-isobutyryloxy-5-ethyl-phenyl]-4-(1-methyl-benzo-imidazol-4-yl)-5-hydroxy-[1,2,4]triazole.   
     
     
         3 . The method of  claim 1 , wherein when Y is —OH or —SH, R 1  and R 2  are selected from the group consisting of an acyl group, a carbamoyl group, an alkoxycarbonyl group, and an alkoxymethyl group. 
     
     
         4 . The method of  claim 1 , wherein R 1  and R 2  are the same. 
     
     
         5 . The method of  claim 1 , wherein R is an optionally substituted carbocyclic aryl group. 
     
     
         6 . The method of  claim 1 , wherein R is an optionally substituted heterocyclic aryl group. 
     
     
         7 . The method of  claim 1 , wherein R has the following general formula: 
       
         
           
           
               
               
           
         
         m is an integer from 0 to 5; and 
         A is an optionally substituted cyclic or non-cyclic amino group, an optionally substituted cyclic or non-cyclic acylamino group, or an optionally substituted cyclic or non-cyclic sulfonylamino group. 
       
     
     
         8 . The method of  claim 1 , wherein R has the following general formula: 
       
         
           
           
               
               
           
         
         m is an integer from 0 to 5; and 
         A is an optionally substituted cyclic or non-cyclic amino group, an acylamino group, or a sulfonylamino group. 
       
     
     
         9 . The method of  claim 1 , wherein X is an optionally substituted C 1-8  alkyl group, an optionally substituted C 1-8  alkoxyl group, or an optionally substituted C 1-8  alkylthio group. 
     
     
         10 . The method of  claim 1 , wherein Y is an acyloxy group, an alkoxycarbonyloxy group, or a carbamoyloxy group. 
     
     
         11 . A method of inhibiting Hsp90 in a cell comprising:
 administering to the cell an effective amount of a compound of formula (1):   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, or a prodrug thereof, wherein: 
         R is an optionally substituted heteroaryl or an optionally substituted aryl; 
         X is an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, cyano, halo, nitro, an optionally substituted cycloalkyl, haloalkyl, optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, an optionally substituted heteroaralkyl, —OR 7 , —SR 7 , —NR 10 R 11 , —OC(O)NR 10   a R 11   a , —NR 7 C(O)NR 10   a R 11   a , —OC(O)R 7   a , —NR 7   b C(O)R 7   b′ , —OC(O)OR 7   c , —NR 7   b C(O)OR 7   b′ , —OCH 2 C(O)NH 2 , —SCH 2 C(O)NH 2 , —NR 7   b S(O) 2 R 7   b′ , —NR 7   b S(O) 2 NR 10   a R 11   a , —C(O)R 7   d , —C(O)OH, —C(O)OR 7   e , —C(O)NR 10   a R 11   a , —S(O) 2 NR 10   a R 11   a , or —S(O) p R 7   f ; 
         R 1  and R 2  are —H, an acyl group, a carbamoyl group, an alkoxycarbonyl group, or an alkoxymethyl group; 
         R 7  is —H, an optionally substituted alkyl, alkenyl, alkynyl, an optionally substituted cycloalkyl, cycloalkenyl, an optionally substituted aryl, heteroaryl, an aralkyl, or an heteraralkyl; 
         R 7   a  is an optionally substituted alkyl, alkenyl, alkynyl, an optionally substituted cycloalkyl, cycloalkenyl, aryl, an aralkyl, or a heteraralkyl; 
         R 7   b  is —H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, or heteroaryl; 
         R 7   b′  is alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, or heteraralkyl; 
         R 7   c  is an optionally substituted alkyl, alkenyl, alkynyl, an optionally substituted cycloalkyl, cycloalkenyl, an aralkyl, or a heteraralkyl; 
         R 7   d  is alkyl, aryl, or heteroaryl; 
         R 7   e  is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, an aralkyl or a heteraralkyl; 
         R 7   f  is an optionally substituted alkyl, alkenyl, alkynyl, an optionally substituted cycloalkyl, cycloalkenyl, an optionally substituted aryl, heteroaryl, an aralkyl, or a heteraralkyl; 
         R 10  and R 11 , for each occurrence, is independently —H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, or heteroaryl; or R 10  and R 11 , taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl; 
         R 10   a  and R 11   a , for each occurrence, is independently —H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, or heteroaryl; 
         Y is —OH, —SH, an optionally substituted acyloxy group, an optionally substituted alkoxycarbonyloxy group, or an optionally substituted carbamoyloxy group; provided that when Y is —OH or —SH at least one of R 1  and R 2  is not hydrogen; and 
         p, for each occurrence, is independently 1 or 2. 
       
     
     
         12 . The method of  claim 11 , wherein the compound is not
 3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-trifluoromethyl-phenyl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-methyl-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(8-methoxy-quinolin-5-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-hydroxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-ethyl-phenyl)-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-chloro-phenyl]-4-(quinolin-5-yl)-5-mercapto-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(2,3-difluoro-phenyl)-5-mercapto-[1,2,4]triazole; or   3-[2-Hydroxy-4-isobutyryloxy-5-ethyl-phenyl]-4-(1-methyl-benzo-imidazol-4-yl)-5-hydroxy-[1,2,4]triazole.   
     
     
         13 . The method of  claim 11 , wherein when Y is —OH or —SH, R 1  and R 2  are selected from the group consisting of an acyl group, a carbamoyl group, an alkoxycarbonyl group, and an alkoxymethyl group. 
     
     
         14 . The method of  claim 11 , wherein R 1  and R 2  are the same. 
     
     
         15 . The method of  claim 11 , wherein X is —OR 7  or —SR 7  with R 7  being pyridyl. 
     
     
         16 . The method of  claim 11 , wherein X is —OC(O)R 7   a  with R 7   a  being phenyl. 
     
     
         17 . The method of  claim 11 , wherein X is —C(O)R 7   d  with R 7   d  being methyl, ethyl, tert-butyl, phenyl or pyridyl. 
     
     
         18 . The method of  claim 11 , wherein X is —S(O) p R 7   f  with R 7   f  being pyridyl. 
     
     
         19 . The method of  claim 11 , wherein X is morpholino group, piperidinyl group, or 4-methylpiperazine-1-yl group. 
     
     
         20 . The method of  claim 11 , wherein X is —OR 7  or —SR 7 , with R 7  being alkyl substituted with an acyl group or an alkoxycarbonyl group. 
     
     
         21 . The method of  claim 11 , wherein R 10  and R 11 , taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl selected from the group consisting of morpholino, piperidinyl, and 4-methylpiperazine-1-yl. 
     
     
         22 . The method of  claim 11 , wherein R is an optionally substituted naphthyl group. 
     
     
         23 . The method of  claim 11 , wherein R is represented by the following formula: 
       
         
           
           
               
               
           
         
         wherein: 
         R 3 , for each occurrence, is independently a substituent selected from the group consisting of alkyl, alkenyl, an alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, halo, cyano, nitro, —NR 10 R 11 , —OR 7 , —C(O)R 7 , —C(O)OR 7 , —OC(O)R 7 , —C(O)NH 2 , —NHC(O)R 7 , —SR 7 , —S(O) p R 7 , —NHS(O) 2 R 7 , or —S(O) 2 NH 2 . 
       
     
     
         24 . The method of  claim 11 , wherein R is an optionally substituted indolyl. 
     
     
         25 . The method of  claim 11 , wherein R is represented by the following formula: 
       
         
           
           
               
               
           
         
         wherein: 
         R 4  is H, a halo, alkyl, alkoxy, or alkyl sulfanyl; and 
         R 5  is H, alkyl, or alkylcarbonyl. 
       
     
     
         26 . The method of  claim 11 , wherein X is a C1-C6 alkyl, a C1-C6 haloalkyl, a C1-C6 alkoxy, a C1-C6 haloalkoxy, a C1-C6 alkyl sulfanyl or a C3-C6 cycloalkyl. 
     
     
         27 . A method of treating cancer in a mammal comprising:
 administering to the mammal an effective amount of a compound of formula (1):   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, or a prodrug thereof, wherein: 
         R is an optionally substituted heterocyclic aryl or an optionally substituted carbocyclic aryl group; 
         R 1  and R 2  are —H, an acyl group, a carbamoyl group, an alkoxycarbonyl group, or an alkoxymethyl group; 
         X is an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, cyano group, halogen atom, nitro group, an optionally substituted cyclic alkyl group, an optionally substituted carbocyclic aryl group, an optionally substituted heterocyclic aryl group, hydroxyl group, an optionally substituted alkoxyl group, an optionally substituted aryloxy group, mercapto group, an optionally substituted alkylthio group, an optionally substituted arylthio group, an optionally substituted amino group, an optionally substituted carbamoyloxy group, an optionally substituted ureido group, an optionally substituted acyloxy group, an optionally substituted acylamino group, an optionally substituted alkoxycarbonyloxy group, an optionally substituted alkoxycarbonylamino group, an optionally substituted sulfonylamino group, an optionally substituted sulfamoylamino group, an optionally substituted acyl group, an optionally substituted carboxyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted carbamoyl group, an optionally substituted sulfamoyl group, an optionally substituted alkylsulfonyl group, an optionally substituted arylsulfonyl group, an optionally substituted alkylsulfinyl group, or an optionally substituted arylsulfinyl group; and 
         Y is —OH, —SH, an optionally substituted acyloxy group, an optionally substituted alkoxycarbonyloxy group, or an optionally substituted carbamoyloxy group; provided that when Y is —OH or —SH at least one of R 1  and R 2  is not hydrogen. 
       
     
     
         28 . The method of  claim 27 , wherein the compound is not
 3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-trifluoromethyl-phenyl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-methyl-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(8-methoxy-quinolin-5-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-hydroxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-ethyl-phenyl)-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-chloro-phenyl]-4-(quinolin-5-yl)-5-mercapto-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(2,3-difluoro-phenyl)-5-mercapto-[1,2,4]triazole; or   3-[2-Hydroxy-4-isobutyryloxy-5-ethyl-phenyl]-4-(1-methyl-benzo-imidazol-4-yl)-5-hydroxy-[1,2,4]triazole.   
     
     
         29 . The method of  claim 27 , wherein cancer being treated is breast cancer. 
     
     
         30 . The method of  claim 27 , wherein when Y is —OH or —SH, R 1  and R 2  are selected from the group consisting of an acyl group, a carbamoyl group, an alkoxycarbonyl group, and an alkoxymethyl group. 
     
     
         31 . The method of  claim 27 , wherein R 1  and R 2  are the same. 
     
     
         32 . The method of  claim 27 , wherein R is an optionally substituted carbocyclic aryl group. 
     
     
         33 . The method of  claim 27 , wherein R is an optionally substituted heterocyclic aryl group. 
     
     
         34 . The method of  claim 27 , wherein R has the following general formula: 
       
         
           
           
               
               
           
         
         m is an integer from 0 to 5; and 
         A is an optionally substituted cyclic or non-cyclic amino group, an optionally substituted cyclic or non-cyclic acylamino group, or an optionally substituted cyclic or non-cyclic sulfonylamino group. 
       
     
     
         35 . The method of  claim 27 , wherein R has the following general formula: 
       
         
           
           
               
               
           
         
         m is an integer from 0 to 5; and 
         A is an optionally substituted cyclic or non-cyclic amino group, an acylamino group, or a sulfonylamino group. 
       
     
     
         36 . The method of  claim 27 , wherein X is an optionally substituted C 1-8  alkyl group, an optionally substituted C 1-8  alkoxyl group, or an optionally substituted C 1-8  alkylthio group. 
     
     
         37 . The method of  claim 27 , wherein Y is an acyloxy group, an alkoxycarbonyloxy group, or a carbamoyloxy group. 
     
     
         38 . A method of treating cancer in a mammal comprising:
 administering to the mammal an effective amount of a compound of formula (1):   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, or a prodrug thereof, wherein: 
         R is an optionally substituted heteroaryl or an optionally substituted aryl; 
         X is an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, cyano, halo, nitro, an optionally substituted cycloalkyl, haloalkyl, optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, an optionally substituted heteroaralkyl, —OR 7 , —SR 7 , —NR 10 R 11 , —OC(O)NR 10   a R 11   a , —NR 7 C(O)NR 10   a R 11   a , —OC(O)R 7   a , —NR 7   b C(O)R 7   b′ , —OC(O)OR 7   c , —NR 7   b C(O)OR 7   b′ , —OCH 2 C(O)NH 2 , —SCH 2 C(O)NH 2 , —NR 7   b S(O) 2 R 7   b′ , —NR 7   b S(O) 2 NR 10   a R 11   a , —C(O)R 7   d , —C(O)OH, —C(O)OR 7   e , —C(O)NR 10   a R 11   a , —S(O) 2 NR 10   a R 11   a , or —S(O) p R 7   f ; 
         R 1  and R 2  are —H, an acyl group, a carbamoyl group, an alkoxycarbonyl group, or an alkoxymethyl group; 
         R 7  is —H, an optionally substituted alkyl, alkenyl, alkynyl, an optionally substituted cycloalkyl, cycloalkenyl, an optionally substituted aryl, heteroaryl, an aralkyl, or an heteraralkyl; 
         R 7   a  is an optionally substituted alkyl, alkenyl, alkynyl, an optionally substituted cycloalkyl, cycloalkenyl, aryl, an aralkyl, or a heteraralkyl; 
         R 7   b  is H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, or heteroaryl; 
         R 7   b′  is alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, or heteraralkyl; 
         R 7   c  is an optionally substituted alkyl, alkenyl, alkynyl, an optionally substituted cycloalkyl, cycloalkenyl, an aralkyl, or a heteraralkyl; 
         R 7   d  is alkyl, aryl, or heteroaryl; 
         R 7   e  is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, an aralkyl, or a heteraralkyl; 
         R 7   f  is an optionally substituted alkyl, alkenyl, alkynyl, an optionally substituted cycloalkyl, cycloalkenyl, an optionally substituted aryl, heteroaryl, an aralkyl, or a heteraralkyl; 
         R 10  and R 11 , for each occurrence, is independently —H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl; or R 10  and R 11 , taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl; 
         R 10   a  and R 11   a   f  for each occurrence, is independently —H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, or heteroaryl; 
         Y is —OH, —SH, an optionally substituted acyloxy group, an optionally substituted alkoxycarbonyloxy group, or an optionally substituted carbamoyloxy group; provided that when Y is —OH or —SH at least one of R 1  and R 2  is not hydrogen; and 
         p, for each occurrence, is independently 1 or 2. 
       
     
     
         39 . The method of  claim 38 , wherein the compound is not
 3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-trifluoromethyl-phenyl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-methyl-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(8-methoxy-quinolin-5-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-hydroxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-ethyl-phenyl)-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-chloro-phenyl]-4-(quinolin-5-yl)-5-mercapto-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(2,3-difluoro-phenyl)-5-mercapto-[1,2,4]triazole; or   3-[2-Hydroxy-4-isobutyryloxy-5-ethyl-phenyl]-4-(1-methyl-benzo-imidazol-4-yl)-5-hydroxy-[1,2,4]triazole.   
     
     
         40 . The method of  claim 38 , wherein cancer being treated is breast cancer. 
     
     
         41 . The method of  claim 38 , wherein when Y is —OH or —SH, R 1  and R 2  are selected from the group consisting of an acyl group, a carbamoyl group, an alkoxycarbonyl group, and an alkoxymethyl group. 
     
     
         42 . The method of  claim 38 , wherein R 1  and R 2  are the same. 
     
     
         43 . The method of  claim 38 , wherein X is —OR 7  or —SR 7  with R 7  being pyridyl. 
     
     
         44 . The method of  claim 38 , wherein X is —OC(O)R 7   a  with R 7   a  being phenyl. 
     
     
         45 . The method of  claim 38 , wherein X is —C(O)R 7   d  with R 7   d  being methyl, ethyl, tert-butyl, phenyl or pyridyl. 
     
     
         46 . The method of  claim 38 , wherein X is —S(O) p R 7   f  with R 7   f  being pyridyl. 
     
     
         47 . The method of  claim 38 , wherein X is morpholino group, piperidinyl group, or 4-methylpiperazine-1-yl group. 
     
     
         48 . The method of  claim 38 , wherein X is —OR 7  or —SR 7  with R 7  being alkyl substituted with an acyl group or an alkoxycarbonyl group. 
     
     
         49 . The method of  claim 38 , wherein R 10  and R 11 , taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl selected from the group consisting of morpholino, piperidinyl, and 4-methylpiperazine-1-yl. 
     
     
         50 . The method of  claim 38 , wherein R is an optionally substituted naphthyl group. 
     
     
         51 . The method of  claim 38 , wherein R is represented by the following formula: 
       
         
           
           
               
               
           
         
         wherein: 
         R 3 , for each occurrence, is independently a substituent selected from the group consisting of alkyl, alkenyl, an alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, halo, cyano, nitro, —NR 10 R 11 , —OR 7 , —C(O)R 7 , —C(O)OR 7 , —OC(O)R 7 , —C(O)NH 2 , —NHC(O)R 7 , —SR 7 , —S(O) p R 7 , —NHS(O) 2 R 7 , or —S(O) 2 NH 2 . 
       
     
     
         52 . The method of  claim 38 , wherein R is an optionally substituted indolyl. 
     
     
         53 . The method of  claim 38 , wherein R is represented by the following formula: 
       
         
           
           
               
               
           
         
         wherein: 
         R 4  is H, a halo, alkyl, alkoxy, or alkyl sulfanyl; and 
         R 5  is H, alkyl, or alkylcarbonyl. 
       
     
     
         54 . The method of  claim 38 , wherein X is a C1-C6 alkyl, a C1-C6 haloalkyl, a C1-C6 alkoxy, a C1-C6 haloalkoxy, a C1-C6 alkyl sulfanyl or a C3-C6 cycloalkyl. 
     
     
         55 . A method of treating cancer in a mammal comprising:
 administering to the mammal an effective amount of a compound of formula (II):   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, or a prodrug thereof, wherein: 
         Y is a hydroxy group, a mercapto group, an optionally substituted amino group, an optionally substituted alkoxyl group, an optionally substituted alkylthio, an optionally substituted carbamoyloxy group, an optionally substituted ureido group, an optionally substituted acyloxy group, an optionally substituted acylamino group, an optionally substituted alkoxycarbonyloxy group, an optionally substituted alkoxycarbonylamino group, an optionally substituted acyl group, an optionally substituted sulfamoyl group, an optionally substituted alkylsulfinyl group, an optionally substituted arylsulfinyl group, or an alkyl sulfonyl group; 
         X is a hydroxy group, a mercapto group, an optionally substituted amino group, an optionally substituted alkyl group, an optionally substituted alkoxyl group, an optionally substituted alkylthio group, an optionally substituted carbamoyloxy group, an optionally substituted ureido group, an optionally substituted acyloxy group, an optionally substituted acylamino group, an optionally substituted alkoxycarbonyloxy group, an optionally substituted alkoxycarbonylamino group, an optionally substituted sulfonylamino group, an optionally substituted carboxyl group, an optionally substituted carbamoyl group, or an optionally substituted sulfamoyl group; 
         R is an optionally substituted carbocyclic or heterocyclic aryl group; and 
         R 1  and R 2  are —H, an acyl group, a carbamoyl group, an alkoxycarbonyl group, or an alkoxymethyl group; 
       
     
     
         56 . The method of  claim 55 , wherein the compound is not
 3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-trifluoromethyl-phenyl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-methyl-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(8-methoxy-quinolin-5-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-hydroxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-ethyl-phenyl)-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-chloro-phenyl]-4-(quinolin-5-yl)-5-mercapto-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(2,3-difluoro-phenyl)-5-mercapto-[1,2,4]triazole; or   3-[2-Hydroxy-4-isobutyryloxy-5-ethyl-phenyl]-4-(1-methyl-benzo-imidazol-4-yl)-5-hydroxy-[1,2,4]triazole.   
     
     
         57 . The method of  claim 55 , wherein the cancer being treated is breast cancer. 
     
     
         58 . The method of  claim 55 , wherein R 1  and R 2  are —OH. 
     
     
         59 . The method of  claim 55 , wherein R 1  and R 2  are the same. 
     
     
         60 . The method of  claim 55 , wherein R has the following general formula: 
       
         
           
           
               
               
           
         
         m is an integer from 0 to 5; and 
         A is an optionally substituted cyclic or non-cyclic amino group, an optionally substituted cyclic or non-cyclic acylamino group, or an optionally substituted cyclic or non-cyclic sulfonylamino group. 
       
     
     
         61 . The method of  claim 55 , wherein R has the following general formula: 
       
         
           
           
               
               
           
         
         m is an integer from 0 to 5; and 
         A is an optionally substituted cyclic or non-cyclic amino group, an acylamino group, or a sulfonylamino group. 
       
     
     
         62 . The method of  claim 55 , wherein Y is a hydroxy group, a mercapto group, an optionally substituted amino group, an alkoxyl group, an alkylthio, a carbamoyloxy group, a ureido group, an acyloxy group, an acylamino group, an alkoxycarbonyloxy group, an alkoxycarbonylamino group, an acyl group, a sulfamoyl group, an alkylsulfinyl group, an arylsulfinyl group, or an alkylsulfonyl group. 
     
     
         63 . A method of treating cancer in a mammal comprising:
 administering to the mammal an effective amount of a compound of formula (II):   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, or a prodrug thereof, wherein: 
         Y is —OH, —SH, —NR 7 H, —OR′ 26 , —O(CH 2 ) m OH, —O(CH 2 ) m SH, —S(CH 2 ) m OH, —S(CH 2 ) m SH, —S(CH 2 ) m NPhH, —OC(O)NR 10 R 11 , —NR 7 C(O)NR 10 R 11 , —OC(O)R 7   a , —NR 2   b C(O)R 2   b′ , —OC(O)OR 7   c , —NR 7   b C(O)OR 7   b′ , —OCH 2 C(O)R 7   d , —SCH 2 C(O)R 7   d , OCH 2 C(O)OR 2   e , —SCH 2 C(O)OR 2   e , —OCH 2 C(O)NH 2 , —SCH 2 C(O)NH 2 , —C(O)R 7   d , —S(O) 2 NR 10 R 11 , or —S(O) p R 7   a ; 
         X is an optionally substituted alkyl, —OH, —SH, —NR 7 H, —OR′ 26 , —SR′ 26 , —NHR′ 26 , —O(CH 2 ) m OH, —O(CH 2 ) m SH, —O(CH 2 ) m NPhH, —S(CH 2 ) m OH, —S(CH 2 ) m SH, —S(CH 2 ) m NPhH, —OC(O)NR 10 R 11 , —NR 7 C(O)NR 10 NR 11 , —OC(O)R 7   a , —NR 2   b C(O)R 7   b′ , —OC(O)OR 7   c , —NR 7   b C(O)OR 7   b′ , —OCH 2 C(O)R 7   d , —SCH 2 C(O)R 7   d , —OCH 2 C(O)OR 7   e , —SCH 2 C(O)OR 7   e , —OCH 2 C(O)NR 10   a R 11   a , —SCH 2 C(O)NR 20   a R 11   a , —NR 7   b S(O) 2 R 7   b′ , —NR 7 S(O) 2 NR 10 R 11 , —C(O)OH, —C(O)NHR 8 , or —S(O) 2 NHR 8 ; 
         m, for each occurrence, is independently, 1, 2, 3 or 4; 
         R 1  and R 2  are —H, an acyl group, a carbamoyl group, an alkoxycarbonyl group, or an alkoxymethyl group; 
         R′ 26 , for each occurrence is, independently, a C 1 -C 6  alkyl; 
         R 7  is —H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, or heteroaryl; 
         R 7   a  is an optionally substituted alkyl, alkenyl, alkynyl, an optionally substituted cycloalkyl, cycloalkenyl, aryl, aralkyl, or heteraralkyl; 
         R 7   b  is —H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, or heteroaryl; 
         R 7   b′  is alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, or heteraralkyl; 
         R 7   c  is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, an aralkyl or a heteraralkyl; 
         R 7   d  is alkyl, aryl, or heteroaryl; 
         R 7   e  is alkyl, cycloalkyl, or aryl; 
         R 8  is —H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, or heteroaryl; 
         R 10  and R 11 , for each occurrence, is independently —H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, or heteroaryl; 
         R 10   a  and R 11   a , for each occurrence, is independently —H, alkyl, or aryl; or R 10   a  and R 11   a , taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl; 
         R is an optionally substituted carbocyclic or heterocyclic aryl group; and 
         p is 1 or 2. 
       
     
     
         64 . The method of  claim 63 , wherein the compound is not
 3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-trifluoromethyl-phenyl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-methyl-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(8-methoxy-quinolin-5-yl)-5-carbamoyloxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-hydroxy-[1,2,4]triazole;   3-(2-Hydroxy-4-ethoxycarbonyoxy-5-ethyl-phenyl)-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-chloro-phenyl]-4-(quinolin-5-yl)-5-mercapto-[1,2,4] triazole;   3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(2,3-difluoro-phenyl)-5-mercapto-[1,2,4]triazole; or   3-[2-Hydroxy-4-isobutyryloxy-5-ethyl-phenyl]-4-(1-methyl-benzo-imidazol-4-yl)-5-hydroxy-[1,2,4]triazole.   
     
     
         65 . The method of  claim 63 , wherein cancer being treated is breast cancer. 
     
     
         66 . The method of  claim 63 , wherein R 1  and R 2  are —OH. 
     
     
         67 . The method of  claim 63 , wherein R 1  and R 2  are the same. 
     
     
         68 . The method of  claim 63 , wherein an optionally substituted carbocyclic aryl group represented by R has the following general formula: 
       
         
           
           
               
               
           
         
         m is an integer from 0 to 5; 
         A is an optionally substituted cyclic or non-cyclic amino group, an optionally substituted cyclic or non-cyclic acylamino group, or an optionally substituted cyclic or non-cyclic sulfonylamino group. 
       
     
     
         69 . The method of  claim 63 , wherein an optionally substituted carbocyclic aryl group represented by R has the following general formula: 
       
         
           
           
               
               
           
         
         m is an integer from 0 to 5; and 
         A is an optionally substituted cyclic or non-cyclic amino group, an acylamino group, or a sulfonylamino group. 
       
     
     
         70 . The method of  claim 63 , wherein X is —OC(O)R 7   a  with R 7   a  being phenyl. 
     
     
         71 . The method of  claim 63 , wherein X is —C(O)R 7   d  with R 7   d  being methyl, ethyl, tert-buthyl, phenyl or pyridyl. 
     
     
         72 . The method of  claim 63 , wherein X is —OCH 2 C(O)OR 7   e  or —SCH 2 C(O)OR 7   e  with R 7   e  being phenyl. 
     
     
         73 . The method of  claim 63 , wherein Y is —OCH 2 C(O)OR 7   e  or —SCH 2 C(O)OR 7   e  with R 7   e  being phenyl. 
     
     
         74 . The method of  claim 63 , wherein X is —OCH 2 C(O)NR 10   a R 11   a  or —SCH 2 C(O)NR 10   a R 11   a  with R 10   a  being methyl and R 11   a  being methyl or with R 10   a  being hydrogen and R 11   a  being phenyl. 
     
     
         75 . The method of  claim 63 , wherein R 10   a  and R 11   a , taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl selected from the group consisting of morpholino, piperidinyl, and 4-methylpiperazine-1-yl. 
     
     
         76 . The method of  claim 63 , wherein Y is a hydroxy group, a mercapto group, an optionally substituted amino group, an alkoxyl group, an alkylthio, a carbamoyloxy group, a ureido group, an acyloxy group, an acylamino group, an alkoxycarbonyloxy group, an alkoxycarbonylamino group, an acyl group, a sulfamoyl group, an alkylsulfinyl group, an arylsulfinyl group, or an alkylsulfonyl group.