Triazole compounds that modulate hsp90 activity

Abstract

The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a composition comprising such a compound.

What is claimed is: 
     
         1 . A method of inhibiting Hsp90 in a cell, comprising administering to the cell an effective amount of a compound represented by the following structural formula: 
       
         
           
           
               
               
           
         
         or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein: 
         R 1 , R 2  and R 3  are independently —OH, —SH, —NR 7 H, —OR 26 , —SR 26 , —O(CH 2 ) m OH, —O(CH 2 ) m SH, —O(CH 2 ) m NR 7 H, —S(CH 2 ) m OH, —S(CH 2 ) m SH, —S(CH 2 ) m NR 7 H, —OC(O)NR 10 R 11 , —SC(O)NR 10 R 11 , —NR 7 C(O)NR 10 R 11 , —OC(O)R 7 , —SC(O)R 7 , —NR 7 C(O)R 7 , —OC(O)OR 7 , —SC(O)OR 7 , —NR 7 C(O)OR 7 , —OCH 2 C(O)R 7 , —SCH 2 C(O)R 7 , —NR 7 CH 2 C(O)R 7 , —OCH 2 C(O)OR 7 , —SCH 2 C(O)OR 7 , —NR 7 CH 2 C(O)OR 7 , —OCH 2 C(O)NR 10 R 11 , —SCH 2 C(O)NR 10 R 11 , —NR 7 CH 2 C(O)NR 10 R 11 , —OS(O) p R 7 , —SS(O) p R 7 , —S(O) p OR 7 , —NR 7 S(O) p R 7 , —OS(O) p NR 10 R 11 , —SS(O) p NR 10 R 11 , —NR 7 S(O) p NR 10 R 11 , —OS(O) p OR 7 , —SS(O) p OR 7 , —NR 7 S(O) p OR 7 , —OC(S)R 7 , —SC(S)R 7 , —NR 7 C(S)R 7 , —OC(S)OR 7 , —SC(S)OR 7 , —NR 7 C(S)OR 7 , —OC(S)NR 10 R 11 , —SC(S)NR 10 R 11 , —NR 7 C(S)NR 10 R 11 , —OC(NR 8 )R 7 , —SC(NR 8 )R 7 , —NR 7 C(NR 8 )R 7 , —OC(NR 8 )OR 7 , —SC(NR 8 )OR 7 , —NR 7 C(NR 8 )OR 7 , —OC(NR 8 )NR 10 R 11 , —SC(NR 8 )NR 10 R 11 , —NR 7 C(NR 8 )NR 10 R 11 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 , provided that at least one of R 1 , R 2  and R 3  is —OP(O)(OH) 2 ; 
         R 5  is —X 20 R 50 , an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; 
         R 7  and R 8 , for each occurrence, is independently, —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; 
         R 10  and R 11 , for each occurrence, is independently —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 10  and R 11 , taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl; 
         R 26  is a lower alkyl; 
         R 50  is an optionally substituted aryl or an optionally substituted heteroaryl; 
         X 20  is a C1-C4 alkyl, NR 7 , C(O), C(S), C(NR 8 ), or S(O) p ; 
         Z is a substituent; 
         p, for each occurrence, is independently, 1 or 2; 
         m for each occurrence, is independently 1, 2, 3, or 4; and 
         n is 0, 1, 2, or 3; and 
         with the proviso that the compound is not 3-hydroxy-4-(5-mercapto-4-(naphthalen-1-yl)-4H-1,2,4-triazol-3-yl)phenyl dihydrogen phosphate. 
       
     
     
         2 . The method of  claim 1 , wherein Z 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. 
     
     
         3 . The method of  claim 1 , wherein the compound is represented by the following structural formula: 
       
         
           
           
               
               
           
         
         wherein R 6  is an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, cyano, halo, nitro, an optionally substituted cycloalkyl, haloalkyl, an 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 R 11 , —SC(O)NR 10 R 11 , —NR 7 C(O)NR 10 R 11 , —OC(O)R 7 , —SC(O)R 7 , —NR 7 C(O)R 7 , —OC(O)OR 7 , —SC(O)OR 7 , —NR 7 C(O)OR 7 , —OCH 2 C(O)R 7 , —SCH 2 C(O)R 7 , —NR 7 CH 2 C(O)R 7 , —OCH 2 C(O)OR 7 , —SCH 2 C(O)OR 7 , —NR 7 CH 2 C(O)OR 7 , —OCH 2 C(O)NR 10 R 11 , —SCH 2 C(O)NR 10 R 11 , —NR 7 CH 2 C(O)NR 10 R 11 , —OS(O) p R 7 , —SS(O) p R 7 , —NR 7 S(O) p R 7 , —OS(O) p NR 10 R 11 , —SS(O) p NR 10 R 11 , —NR 7 S(O) p NR 10 R 11 , —OS(O) p OR 7 , —SS(O) p OR 7 , —NR 7 S(O) p OR 7 , —OC(S)R 7 , —SC(S)R 7 , —NR 7 C(S)R 7 , —OC(S)OR 7 , —SC(S)OR 7 , —NR 7 C(S)OR 7 , —OC(S)NR 10 R 11 , —SC(S)NR 10 R 11 , —NR 7 C(S)NR 10 R 11 , —OC(NR 8 )R 7 , —SC(NR 8 )R 7 , —NR 7 C(NR 8 )R 7 , —OC(NR 8 )OR 7 , —SC(NR 8 )OR 7 , —NR 7 C(NR 8 )OR 7 , —OC(NR 8 )NR 10 R 11 , —SC(NR 8 )NR 10 R 11 , —NR 7 C(NR 8 )NR 10 R 11 , —C(O)R D , —C(O)OR 7 , —C(O)NR 10 R 11 , —C(O)SR 7 , —C(S)R 7 , —C(S)OR 7 , —C(S)NR 10 R 11 , —C(S)SR 7 , —C(NR 8 )OR 7 , —C(NR 8 )R 7 , —C(NR 8 )NR 10 R 11 , —C(NR 8 )SR 7 , —S(O) p OR 7 , —S(O) p NR 10 R 11 , or —S(O) p R 7 . 
       
     
     
         4 . The method of  claim 1 , wherein one of R 1 , R 2 , or R 3  is —OP(O)(OH) 2 . 
     
     
         5 . The method of  claim 3 , wherein the compound is represented by the following structural formula: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 5 , wherein R 5  is represented by the following formula: 
       
         
           
           
               
               
           
         
         wherein: 
         R 9 , for each occurrence, is independently a substituent selected from the group consisting of an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, hydroxyalkyl, alkoxyalkyl, halo, cyano, nitro, guanadino, a haloalkyl, a heteroalkyl, —NR 10 R 11 , —OR 7 , —C(O)R D , —C(O)OR 7 , —OC(O)R 7 , —C(O)NR 10 R 11 , —NR 8 C(O)R 7 , —SR 7 , —S(O) p R 7 , —OS(O) p R 7 , —S(O) p OR 7 , —NR 8 S(O) p R 7 , or —S(O) p NR 10 R 11 , —S(O) p OR 7 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 ; 
         or two R 9  groups taken together with the carbon atoms to which they are attached form a fused ring; and 
         q is zero or an integer from 1 to 7. 
       
     
     
         7 . The method of  claim 5 , wherein R 5  is represented by the following formula: 
       
         
           
           
               
               
           
         
         wherein: 
         R 33  is a halo, lower alkyl, a lower alkoxy, a lower haloalkyl, a lower haloalkoxy, and lower alkyl sulfanyl; 
         R 34  is H, a lower alkyl, or a lower alkylcarbonyl; and 
         Ring B and Ring C are optionally substituted with one or more substituents. 
       
     
     
         8 . The method of  claim 5 , wherein R 5  is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein: 
         X 6 , for each occurrence, is independently CH, CR 9 , N, N(O), N + (R 17 ), provided that at least three X 6  groups are independently selected from CH and CR 9 ; 
         X 7 , for each occurrence, is independently CH, CR 9 , N, N(O), N + (R 17 ), provided that at least three X 7  groups are independently selected from CH and CR 9 ; 
         X 8 , for each occurrence, is independently CH 2 , CHR 9 , C(R 9 ) 2 , S, S(O)p, NR 7 , or NR 17 ; 
         X 9 , for each occurrence, is independently N or CH; 
         X 10 , for each occurrence, is independently CH, CR 9 , N, N(O), N + (R 17 ), provided that at least one X 10  is selected from CH and CR 9 ; 
         R 9 , for each occurrence, is independently a substituent selected from the group consisting of an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, hydroxyalkyl, alkoxyalkyl, halo, cyano, nitro, guanadino, a haloalkyl, a heteroalkyl, —NR 10 R 11 , —OR 7 , —C(O)R 7 , —C(O)OR 7 , —OC(O)R 7 , —C(O)NR 10 R 11 , —NR 8 C(O)R 7 , —SR 7 , —S(O) p R 7 , —OS(O) p R 7 , —S(O) p OR 7 , —NR 8 S(O) p R 7 , or —S(O) p NR 10 R 11 , —S(O) p OR 7 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 , —S(O) p OR 7 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 ; 
         or two R 9  groups taken together with the carbon atoms to which they are attached form a fused ring; and 
         R 17 , for each occurrence, is independently —H, an alkyl, an aralkyl, —C(O)R 7 , —C(O)OR 7 , or —C(O)NR 10 R 11 . 
       
     
     
         9 . The method of  claim 8 , wherein R 5  is an optionally substituted indolyl, an optionally substituted benzoimidazolyl, an optionally substituted indazolyl, an optionally substituted 3H-indazolyl, an optionally substituted indolizinyl, an optionally substituted quinolinyl, an optionally substituted isoquinolinyl, an optionally substituted benzoxazolyl, an optionally substituted benzo[1,3]dioxolyl, an optionally substituted benzofuryl, an optionally substituted benzothiazolyl, an optionally substituted benzo[d]isoxazolyl, an optionally substituted benzo[d]isothiazolyl, an optionally substituted thiazolo[4,5-c]pyridinyl, an optionally substituted thiazolo[5,4-c]pyridinyl, an optionally substituted thiazolo[4,5-b]pyridinyl, an optionally substituted thiazolo[5,4-b]pyridinyl, an optionally substituted oxazolo[4,5-c]pyridinyl, an optionally substituted oxazolo[5,4-c]pyridinyl, an optionally substituted oxazolo[4,5-b]pyridinyl, an optionally substituted oxazolo[5,4-b]pyridinyl, an optionally substituted imidazopyridinyl, an optionally substituted benzothiadiazolyl, benzoxadiazolyl, an optionally substituted benzotriazolyl, an optionally substituted tetrahydroindolyl, an optionally substituted azaindolyl, an optionally substituted quinazolinyl, an optionally substituted purinyl, an optionally substituted imidazo[4,5-a]pyridinyl, an optionally substituted imidazo[1,2-a]pyridinyl, an optionally substituted 3H-imidazo[4,5-b]pyridinyl, an optionally substituted 1H-imidazo[4,5-b]pyridinyl, an optionally substituted 1H-imidazo[4,5-c]pyridinyl, an optionally substituted 3H-imidazo[4,5-c]pyridinyl, an optionally substituted pyridopyrdazinyl, and optionally substituted pyridopyrimidinyl, an optionally substituted pyrrolo[2,3]pyrimidyl, an optionally substituted pyrazolo[3,4]pyrimidyl an optionally substituted cyclopentaimidazolyl, an optionally substituted cyclopentatriazolyl, an optionally substituted pyrrolopyrazolyl, an optionally substituted pyrroloimidazolyl, an optionally substituted pyrrolotriazolyl, or an optionally substituted benzo(b)thienyl. 
     
     
         10 . The method of  claim 5 , wherein R 5  is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein: 
         X 11 , for each occurrence, is independently CH, CR 9 , N, N(O), or N + (R 17 ); 
         X 12 , for each occurrence, is independently CH, CR 9 , N, N(O), N + (R 17 ), provided that at least one X 12  group is independently selected from CH and CR 9 ; 
         X 13 , for each occurrence, is independently O, S, S(O)p, NR 7 , or NR 17 ; 
         R 9 , for each occurrence, is independently a substituent selected from the group consisting of an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, halo, cyano, nitro, guanadino, a hydroxyalkyl, alkoxyalkyl, haloalkyl, a heteroalkyl, —NR 10 R 11 , —OR 7 , —C(O)R 7 , —C(O)OR 7 , —OC(O)R 7 , —C(O)NR 10 R 11 , —NR 8 C(O)R 7 , —SR 7 , —S(O) p R 7 , —OS(O) p R 7 , —S(O) p OR 7 , —NR 8 S(O) p R 7 , or —S(O) p NR 10 R 11 , —S(O) p OR 7 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 , —S(O) p OR 7 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 ; 
         or two R 9  groups taken together with the carbon atoms to which they are attached form a fused ring; and 
         R 17 , for each occurrence, is independently an alkyl or an aralkyl. 
       
     
     
         11 . A method of treating a non-Hodgkin's lymphoma in a mammal, comprising administering to the mammal an effective amount of a compound represented by the following structural formula: 
       
         
           
           
               
               
           
         
         or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein: 
         R 1 , R 2  and R 3  are independently —OH, —SH, —NR 7 H, —OR 26 , —SR 26 , —O(CH 2 ) m OH, —O(CH 2 ) m SH, —O(CH 2 ) m NR 7 H, —S(CH 2 ) m OH, —S(CH 2 ) m SH, —S(CH 2 ) m NR 7 H, —OC(O)NR 10 R 11 , —SC(O)NR 10 R 11 , —NR 7 C(O)NR 10 R 11 , —OC(O)R 7 , —SC(O)R 7 , —NR 7 C(O)R 7 , —OC(O)OR 7 , —SC(O)OR 7 , —NR 7 C(O)OR 7 , —OCH 2 C(O)R 7 , —SCH 2 C(O)R 7 , —NR 7 CH 2 C(O)R 7 , —OCH 2 C(O)OR 7 , —SCH 2 C(O)OR 7 , —NR 7 CH 2 C(O)OR 7 , —OCH 2 C(O)NR 10 R 11 , —SCH 2 C(O)NR 10 R 11 , —NR 7 CH 2 C(O)NR 10 R 11 , —OS(O) p R 7 , —SS(O) p R 7 , —S(O) p OR 7 , —NR 7 S(O) p R 7 , —OS(O) p NR 10 R 11 , —SS(O) p NR 10 R 11 , —NR 7 S(O) p NR 10 R 11 , —OS(O) p OR 7 , —SS(O) p OR 7 , —NR 7 S(O) p OR 7 , —OC(S)R 7 , —SC(S)R 7 , —NR 7 C(S)R 7 , —OC(S)OR 7 , —SC(S)OR 7 , —NR 7 C(S)OR 7 , —OC(S)NR 10 R 11 , —SC(S)NR 10 R 11 , —NR 7 C(S)NR 10 R 11 , —OC(NR 8 )R 7 , —SC(NR 8 )R 7 , —NR 7 C(NR 8 )R 7 , —OC(NR 8 )OR 7 , —SC(NR 8 )OR 7 , —NR 7 C(NR 8 )OR 7 , —OC(NR 8 )NR 10 R 11 , —SC(NR 8 )NR 10 R 11 , —NR 7 C(NR 8 )NR 10 R 11 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 , provided that at least one of R 1 , R 2  and R 3  is —OP(O)(OH) 2 ; 
         R 5  is —X 20 R 50 , an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; 
         R 7  and R 8 , for each occurrence, is independently, —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; 
         R 10  and R 11 , for each occurrence, is independently —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 10  and R 11 , taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl; 
         R 26  is a lower alkyl; 
         R 50  is an optionally substituted aryl or an optionally substituted heteroaryl; 
         X 20  is a C1-C4 alkyl, NR 7 , C(O), C(S), C(NR 8 ), or S(O) p ; 
         Z is a substituent; 
         p, for each occurrence, is independently, 1 or 2; 
         m for each occurrence, is independently 1, 2, 3, or 4; and 
         n is 0, 1, 2, or 3; and 
         with the proviso that the compound is not 3-hydroxy-4-(5-mercapto-4-(naphthalen-1-yl)-4H-1,2,4-triazol-3-yl)phenyl dihydrogen phosphate. 
       
     
     
         12 . The method of  claim 11 , wherein Z 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. 
     
     
         13 . The method of  claim 11 , wherein the compound is represented by the following structural formula: 
       
         
           
           
               
               
           
         
         wherein R 6  is an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, cyano, halo, nitro, an optionally substituted cycloalkyl, haloalkyl, an 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 R 11 , —SC(O)NR 10 R 11 , —NR 7 C(O)NR 10 R 11 , —OC(O)R 7 , —SC(O)R 7 , —NR 7 C(O)R 7 , —OC(O)OR 7 , —SC(O)OR 7 , —NR 7 C(O)OR 7 , —OCH 2 C(O)R 7 , —SCH 2 C(O)R 7 , —NR 7 CH 2 C(O)R 7 , —OCH 2 C(O)OR 7 , —SCH 2 C(O)OR 7 , —NR 7 CH 2 C(O)OR 7 , —OCH 2 C(O)NR 10 R 11 , —SCH 2 C(O)NR 10 R 11 , —NR 7 CH 2 C(O)NR 10 R 11 , —OS(O) p R 7 , —SS(O) p R 7 , —NR 7 S(O) p R 7 , —OS(O) p NR 10 R 11 , —SS(O) p NR 10 R 11 , —NR 7 S(O) p NR 10 R 11 , —OS(O) p OR 7 , —SS(O) p OR 7 , —NR 7 S(O) p OR 7 , —OC(S)R 7 , —SC(S)R 7 , —NR 7 C(S)R 7 , —OC(S)OR 7 , —SC(S)OR 7 , —NR 7 C(S)OR 7 , —OC(S)NR 10 R 11 , —SC(S)NR 10 R 11 , —NR 7 C(S)NR 10 R 11 , —OC(NR 8 )R 7 , —SC(NR 8 )R 7 , —NR 7 C(NR 8 )R 7 , —OC(NR 8 )OR 7 , —SC(NR 8 )OR 7 , —NR 7 C(NR 8 )OR 7 , —OC(NR 8 )NR 10 R 11 , —SC(NR 8 )NR 10 R 11 , —NR 7 C(NR 8 )NR 10 R 11 , —C(O)R 11 , —C(O)OR 7 , —C(O)NR 10 R 11 , —C(O)SR 7 , —C(S)R 7 , —C(S)OR 7 , —C(S)NR 10 R 11 , —C(S)SR 7 , —C(NR 8 )OR 7 , —C(NR 8 )R 7 , —C(NR 8 )NR 10 R 11 , —C(NR 8 )SR 7 , —S(O) p OR 7 , —S(O) p NR 10 R 11 , or —S(O) p R 7 . 
       
     
     
         14 . The method of  claim 11 , wherein one of R 1 , R 2 , or R 3  is —OP(O)(OH) 2 . 
     
     
         15 . The method of  claim 14 , wherein the compound is represented by the following structural formula: 
       
         
           
           
               
               
           
         
       
     
     
         16 . The method of  claim 15 , wherein R 5  is represented by the following formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 9 , for each occurrence, is independently a substituent selected from the group consisting of an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, hydroxyalkyl, alkoxyalkyl, halo, cyano, nitro, guanadino, a haloalkyl, a heteroalkyl, —NR 10 R 11 , —OR 7 , —C(O)R 11 , —C(O)OR 7 , —OC(O)R 7 , —C(O)NR 10 R 11 , —NR 8 C(O)R 7 , —SR 7 , —S(O) p R 7 , —OS(O) p R 7 , —S(O) p OR 7 , —NR 8 S(O) p R 7 , or —S(O) p NR 10 R 11 , —S(O) p OR 7 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 ; 
 or two R 9  groups taken together with the carbon atoms to which they are attached form a fused ring; and 
 q is zero or an integer from 1 to 7. 
 
     
     
         17 . The method of  claim 15 , wherein R 5  is represented by the following formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 33  is a halo, lower alkyl, a lower alkoxy, a lower haloalkyl, a lower haloalkoxy, and lower alkyl sulfanyl; 
 R 34  is H, a lower alkyl, or a lower alkylcarbonyl; and 
 Ring B and Ring C are optionally substituted with one or more substituents. 
 
     
     
         18 . The method of  claim 15 , wherein R 5  is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       wherein:
 X 6 , for each occurrence, is independently CH, CR 9 , N, N(O), N + (R 17 ), provided that at least three X 6  groups are independently selected from CH and CR 9 ; 
 X 7 , for each occurrence, is independently CH, CR 9 , N, N(O), N + (R 17 ), provided that at least three X 7  groups are independently selected from CH and CR 9 ; 
 X 8 , for each occurrence, is independently CH 2 , CHR 9 , C(R 9 ) 2 , S, S(O)p, NR 7 , or NR 17 ; 
 X 9 , for each occurrence, is independently N or CH; 
 X 10 , for each occurrence, is independently CH, CR 9 , N, N(O), N + (R 17 ), provided that at least one X 10  is selected from CH and CR 9 ; 
 R 9 , for each occurrence, is independently a substituent selected from the group consisting of an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, hydroxyalkyl, alkoxyalkyl, halo, cyano, nitro, guanadino, a haloalkyl, a heteroalkyl, —NR 10 R 11 , —OR 7 , —C(O)R 7 , —C(O)OR 7 , —OC(O)R 7 , —C(O)NR 10 R 11 , —NR 8 C(O)R 7 , —SR 7 , —S(O) p R 7 , —OS(O) p R 7 , —S(O) p OR 7 , —NR 8 S(O) p R 7 , or —S(O) p NR 10 R 11 , —S(O) p OR 7 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 , —S(O) p OR 7 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 ; 
 or two R 9  groups taken together with the carbon atoms to which they are attached form a fused ring; and 
 R 17 , for each occurrence, is independently —H, an alkyl, an aralkyl, —C(O)R 7 , —C(O)OR 7 , or —C(O)NR 10 R 11 . 
 
     
     
         19 . The method of  claim 18 , wherein R 5  is an optionally substituted indolyl, an optionally substituted benzoimidazolyl, an optionally substituted indazolyl, an optionally substituted 3H-indazolyl, an optionally substituted indolizinyl, an optionally substituted quinolinyl, an optionally substituted isoquinolinyl, an optionally substituted benzoxazolyl, an optionally substituted benzo[1,3]dioxolyl, an optionally substituted benzofuryl, an optionally substituted benzothiazolyl, an optionally substituted benzo[d]isoxazolyl, an optionally substituted benzo[d]isothiazolyl, an optionally substituted thiazolo[4,5-c]pyridinyl, an optionally substituted thiazolo[5,4-c]pyridinyl, an optionally substituted thiazolo[4,5-b]pyridinyl, an optionally substituted thiazolo[5,4-b]pyridinyl, an optionally substituted oxazolo[4,5-c]pyridinyl, an optionally substituted oxazolo[5,4-c]pyridinyl, an optionally substituted oxazolo[4,5-b]pyridinyl, an optionally substituted oxazolo[5,4-b]pyridinyl, an optionally substituted imidazopyridinyl, an optionally substituted benzothiadiazolyl, benzoxadiazolyl, an optionally substituted benzotriazolyl, an optionally substituted tetrahydroindolyl, an optionally substituted azaindolyl, an optionally substituted quinazolinyl, an optionally substituted purinyl, an optionally substituted imidazo[4,5-a]pyridinyl, an optionally substituted imidazo[1,2-a]pyridinyl, an optionally substituted 3H-imidazo[4,5-b]pyridinyl, an optionally substituted 1H-imidazo[4,5-b]pyridinyl, an optionally substituted 1H-imidazo[4,5-c]pyridinyl, an optionally substituted 3H-imidazo[4,5-c]pyridinyl, an optionally substituted pyridopyrdazinyl, and optionally substituted pyridopyrimidinyl, an optionally substituted pyrrolo[2,3]pyrimidyl, an optionally substituted pyrazolo[3,4]pyrimidyl an optionally substituted cyclopentaimidazolyl, an optionally substituted cyclopentatriazolyl, an optionally substituted pyrrolopyrazolyl, an optionally substituted pyrroloimidazolyl, an optionally substituted pyrrolotriazolyl, or an optionally substituted benzo(b)thienyl. 
     
     
         20 . The method of  claim 15 , wherein R 5  is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       wherein:
 X 11 , for each occurrence, is independently CH, CR 9 , N, N(O), or N + (R 17 ); 
 X 12 , for each occurrence, is independently CH, CR 9 , N, N(O), N + (R 17 ), provided that at least one X 12  group is independently selected from CH and CR 9 ; 
 X 13 , for each occurrence, is independently O, S, S(O)p, NR 7 , or NR 17 ; 
 R 9 , for each occurrence, is independently a substituent selected from the group consisting of an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, halo, cyano, nitro, guanadino, a hydroxyalkyl, alkoxyalkyl, haloalkyl, a heteroalkyl, —NR 10 R 11 , —OR 7 , —C(O)R 7 , —C(O)OR 7 , —OC(O)R 7 , —C(O)NR 10 R 11 , —NR 8 C(O)R 7 , —SR 7 , —S(O) p R 7 , —OS(O) p R 7 , —S(O) p OR 7 , —NR 8 S(O) p R 7 , or —S(O) p NR 10 R 11 , —S(O) p OR 7 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 , —S(O) p OR 7 , —OP(O)(OR 7 ) 2 , or —SP(O)(OR 7 ) 2 ; 
 or two R 9  groups taken together with the carbon atoms to which they are attached form a fused ring; and 
 R 17 , for each occurrence, is independently an alkyl or an aralkyl. 
 
     
     
         21 . The method of  claim 11 , wherein the non-Hodgkin's lymphoma is a B-cell non-Hodgkin's lymphoma. 
     
     
         22 . The method of  claim 21 , wherein the B-cell non-Hodgkin's lymphoma is selected from the group consisting of Burkitt's lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, nodal marginal zone B-cell lymphoma, plasma cell neoplasms, small lymphocytic lymphoma/chronic lymphocytic leukemia, mantle cell lymphoma, and lymphoplamacytic lymphoma/Waldenstrom macroglobulinemia. 
     
     
         23 . The method of  claim 11 , wherein the non-Hodgkin's lymphoma is a T-cell non-Hodgkin's lymphoma. 
     
     
         24 . The method of  claim 23 , wherein the T-cell non-Hodgkin's lymphoma is selected from the group consisting of anaplastic large-cell lymphoma, precursor-T-cell lymphoblastic leukemia/lymphoma, unspecified peripheral T-cell lymphoma, and angioimmunoblastic T-cell lymphoma.