US 2008/0176840 A1 · Triazole compounds that modulate Hsp90 activity

A compound represented by the following structural formula:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
R1, R2, and R3 are each, independently, —OH, —SH, —NHR7, —OR26, —SR26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R5 is an optionally substituted alkyl;
an optionally substituted heteroaryl or an optionally substituted aryl;
R6 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R7 and R8, 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R26 is a lower alkyl;
p, for each occurrence, is independently, 1 or 2;
and
m, for each occurrence, is independently, 1, 2, 3 or 4.

9 more elements

A compound represented by the following structural formula:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or aprodrug thereof, wherein:
R11 is, —NHR7, —NHC(O)NR10,OR11, —NHC(O)R7, —NHC(O)OR7, —NHCH2C(O)R7, —NHCH2C(O)OR7, —NHCH2C(O)NR10R11, —NHS(O)pR7, —NHS(O)pNR10R11, —NHS(O)pOR7, —NHC(S)R7, —NHC(S)OR7, —NHC(S)NR10R11, —NHC(NR8)R7, —NHC(NR8)OR7, or —NHC(NR8)NR10R11;
R2 is —OH, —SH, —NR7H, —OR26, —SR26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R′3 is —OH, —SH, or —NHR7;
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
R7 and R8, 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R26 is a lower alkyl;
Z is a substituent;
p, for each occurrence, is independently, 1 or 2;
m, for each occurrence, is independently, 1, 2, 3 or 4;
t is 0, 1, 2, or 3;
and
with the proviso that the compound is not
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-methoxy-phenyl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(naphthalen-1-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-phenyl-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(2,3-difluorophenyl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(quinolin-5-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(3-methyl-quinolin-5-yl)-5-carboxyamino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-(1-methyl-2-chloro-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-[3,5-di-(trifluoromethyl)-phenyl]-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-trifluoromethyl-phenyl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-(sulfamoylamino)-[1,2,4]triazole, or
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-isopropylphenyl)-5-(thiocarboxyamino)-[1,2,4]triazole.

27 more elements

A compound represented by the following structural formula:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
X is —O— or —S—;
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
R16 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R7 and R8, 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R′17, R18, and R19 are each, independently, —H, —C(O)R22, or (alk)O(alk);
provided that at least one of R′17, R18, or R19 is not —H;
R22, for each occurrence is independently optionally substituted alkyl, optionally substituted aryl, —O(alk), amino, alkyl amino, or dialkyl amino;
alk is a lower alkyl;
p, for each occurrence, is independently 1 or 2;
with the proviso that the compound is not
3-(2-Hydroxy-4-methoxymethyoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2-Hydroxy-4-(2-hydroxy-ethoxy)-phenyl]-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(naphthalen-1-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Dihydroxy-phenyl)-4-(naphthalen-1-yl)-5-(dimethylcarbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diethoxycarbonyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethoxycarbonylsulfanyl)-[1,2,4]triazole;
3-(2,4-Di-isobutyryloxy-phenyl)-4-(naphthalen-1-yl)-5-(isobutyrylsulfanyl)-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(quinolin-5-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-(acetylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-(2,4-Diethylcarbamoyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethylcarbamoylsulfanyl)-[1,2,4]triazole;
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.

30 more elements

A compound represented by the following structural formula:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
X′ is —O—O— or —S—S—;
R′2 and R′3 are, independently, —OH, —SH, or —NHR7;
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
R′6 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R7 and R8, 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
p, for each occurrence, is independently 1 or 2.

6 more elements

A compound represented by the following structural formula:

a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
R70, R′2, and R′3 are, independently, —OH, —SH, or —NHR7;
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
R′6 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R7 and R8, 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R20 is C(O)Ry;
Ry is an optionally substituted alkyl;
p, for each occurrence, is independently 1 or 2.

7 more elements

A compound represented by the following structural formula:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
X is —O— or —S—;
X1 is O or S;
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
R′6 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R7 and R8, 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R71 and R72 are each, independently, —H, —C(O)R22, or (alk)O(alk);
R22, for each occurrence is independently optionally substituted alkyl, optionally substituted aryl, —O(alk), amino, alkyl amino, or dialkyl amino;
R23 is —C(O)R22 or -alk-O—C(O)R22;
alk is a lower alkyl;
p, for each occurrence, is independently 1 or 2.

10 more elements

A compound represented by structural formula (XXI):

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate, or a prodrug thereof, wherein:
ring A is optionally further substituted with one or two independently selected substituents in addition to R3;
ring E is aromatic or non-aromatic;
X16 is —O—, —NR7—, or —S—;
Y is —CR38R′39)k—, —C(O)—, —C(S)—, —C(NR8)—, —CR7═, —O—, —NR7—, —N═, or —S—;
Z′ is —(CR38R′39)k—, ═CR7—, —O—, —S—, —NR7—, ═N—, or —CR′40═CR′41—;
R100 and R3 are each, independently, —OH, —SH, —NR7H, —OR′26, —SR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R′5 is an optionally substituted aryl or an optionally substituted heteroaryl;
R7 and R8, for each occurrence, are, 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;
R10 and R11, for each occurrence, are 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R′26, for each occurrence is, independently, a C1-C6 alkyl;
R38 and R′39, for each occurrence, are 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, an optionally substituted heteroaralkyl, halo, cyano, nitro, guanadino, a haloalkyl, a heteroalkyl, alkoxy, haloalkoxy, —NR10R11, —OR7, —C(O)R7, —C(O)OR7, —C(S)R7, —C(O)SR7, —C(S)SR7, —C(S)OR7, —C(S)NR10R11, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —OC(O)R7, —OC(O)OR7, —OC(S)OR7, —OC(NR8)OR7, —SC(O)R7, —SC(O)OR7, —SC(NR8)OR7, —OC(S)R7, —SC(S)R7, —SC(S)OR7, —OC(O)NR10R11, —OC(S)NR10R11, —OC(NR8)NR10R11, —SC(O)NR10R11, —SC(NR8)NR10R11, —SC(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —C(O)NR10R11, —NR8C(O)R7, —NR7C(S)R7, —NR7C(S)OR7, —NR7C(NR8)R7, —NR7C(O)OR7, —NR7C(NR8)OR7, —NR7C(O)NR10R11, —NR7C(S)NR10R11, —NR7C(NR8)NR10R11, —SR7, —S(O)pR7, —OS(O)pR7, —OS(O)pOR7, —OS(O)pNR10R11, —S(O)pOR7, —NR8S(O)pR7, —NR7S(O)pNR10R11, —NR7S(O)pOR7, —S(O)pNR10R11, —SS(O)pR7, —SS(O)pOR7, —SS(O)pNR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
or R38 and R′39 together with the carbon or carbon atoms to which they are attached form a three to eight membered cycloalkyl or a three to eight membered cycloalkenyl;
R′40 and R′41, for each occurrence, are, 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′40 and R′41, together with the carbon atoms to which they are attached form a three to eight membered cycloalkenyl;
p, for each occurrence, is, independently, 1 or 2;
and
m, for each occurrence, is independently, 1, 2, 3, or 4;
and
k is 1 or 2;
provided that when R′5 is p-chlorophenyl, rings A and E together are not benzofuranyl.

20 more elements

A compound represented by structural formula (XXVIII):

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
ring F is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to R3;
ring G is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to -T1-V1-T2-V2;
R100 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R103 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26, O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)OH, —C(O)NHR8, —C(O)SH, —S(O)OH, —S(O)2OH, —S(O)NHR8, —S(O)2NHR8, —OP(O)(OR7)2 or —SP(O)(OR7)2;
R7 and R8, 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 heteroaralkyl;
R10 and R11, 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 heteroaralkyl;
or R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R′26 is a C1-C6 alkyl;
T1 is absent or a C1-C4 alkylene;
T2 is absent or a C1-C4 alkylene, V1 is absent and V2 is —NRaRb, NRaS(O)2 R**, —S(O)NRaRb, S(O)2NRaRb or C(O)NRaRb;
or
T2 is absent or a C1-C4 alkylene, V1 is —O—, —S—, —N(R*)— or —C(O)N(R*)— and V2 is —S(O)NRaRb, —S(O)2NRaRb or —C(O)NRaRb;
or
T2 is a C2-C4 alkylene, V1 is —O—, —S, —N(R*)—, —C(O)O—, C(O)N(R*)— and V2 is —NRaRb, or —NRaS(O)2R**;
each R* is independently —H or C1-C3 alkyl;
each R** 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 heteroaralkyl;
Ra and Rb, for each occurrence, are 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 or heteroaryl, or an optionally substituted aralkyl;
or Ra and Rb, taken together with the nitrogen to which they are attached, form an optionally substituted heteroaryl or heterocyclyl;
p, for each occurrence, is independently, 0, 1 or 2;
and
m, for each occurrence, is independently, 1, 2, 3 or 4;
wherein when T1, T2 and V, are absent and V2 is —NRaRb then ring G is not phenyl, and when T1, T2 and V1 are absent and V2 is —C(O)NRaRb then ring G is not naphthyl or indolyl.

20 more elements

A compound represented by a structural formula selected from:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
ring G is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to -T1-V1-T2-V2;
X14 is O, S or NR7;
R100 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —S(O)pOR7, —OP(O)(OR7)2 or —SP(O)(OR7)2;
R103 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)OH, —C(O)NHR8, —C(O)SH, —S(O)OH, —S(O)2OH, —S(O)NHR8, —S(O)2NHR8, —S(O)pOR7, —OP(O)(OR7)2 or —SP(O)(OR7)2;
R7 and R8, 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R′22, 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, a haloalkyl, —C(O)R7, —C(O)OR7, —OC(O)R7, —C(O)NR10R11, —NR8C(O)R7, —S(O)pR7, —S(O)pOR7 or —S(O)pNR10R11;
and
R′23 and R′24, for each occurrence, is independently —H, an optionally substituted alky, 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, halo, cyano, nitro, guanadino, a haloalkyl, a heteroalkyl, —NR10R11, —OR7, —C(O)R7, —C(O)OR7, —OC(O)R7, —C(O)NR10R11, —NR8C(O)R7, —SR7, —S(O)pR7, —OS(O)pR7, —S(O)pOR7, —NR8S(O)pR7 or —S(O)pNR10R11;
R′26 is a C1-C6 alkyl;
Ra and Rb, 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 or heteroaryl, an optionally substituted aralkyl;
or Ra and Rb, taken together with the nitrogen to which they are attached, form an optionally substituted heteroaryl or heterocyclyl;
T1 is absent or a C1-C4 alkylene;
T2 is absent or a C1-C4 alkylene, V, is absent and V2 is —NRaRb, —NRaS(O)2 R**, —S(O)NRaRb, S(O)2NRaRb or C(O)NRaRb;
or
T2 is absent or a C1-C4 alkylene, V, is —O—, —S—, —N(R*)— or —C(O)N(R*)— and V2 is —S(O)NRaRb, S(O)2NRaRb or C(O)NRaRb;
or
T2 is a C2-C4 alkylene, V, is —O—, —S, —N(R*)—, —C(O)O—, C(O)N(R*)— and V2 is —NRaRb, or —NRaS(O)2R**;
each R* is independently —H or C1-C3 alkyl;
each R** 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 heteroaralkyl;
p, for each occurrence, is independently, 0, 1 or 2;
and
m, for each occurrence, is independently, 1, 2, 3 or 4.

22 more elements

A method of inhibiting Hsp90 in a cell, comprising administering to the cell an effective amount of a compound selected from the group consisting of:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
R1, R2, and R3 are each, independently, —OH, —SH, —NHR7, —OR26, —SR26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mN7H, —S(CH2)mOH, S(CH2)mSH —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2 or —SP(O)(OR7)2;
R5 is an optionally substituted alkyl:
an optionally substituted heteroaryl or an optionally substituted aryl;
R6 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)R7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7—C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R7 and R8, 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:
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R26 is a lower alkyl:
p, for each occurrence, is independently, 1 or 2:
m, for each occurrence, is independently, 1, 2, 3 or 4;
R′1 is, —NHR7, —NHC(O)NR10R11, —NHC(O)R7, —NHC(O)OR7, —NHCH2C(O)R7, —NHCH2C(O)OR7, —NHCH2C(O)NR10R11, —NHS(O)pR7, —NHS(O)pNR10R11, —NHS(O)pOR7, —NHC(S)R7, —NHC(S)OR7, —NHC(S)NR10R11, —NHC(NR8)R7, —NHC(NR8)OR7, or —NHC(NR8)NR10R11:
R′3 is —OH, —SH, or —NHR7, —R′5 is an optionally substituted heteroaryl or an optionally substituted aryl:
Z is a substituent;
t is 0, 1, 2, or 3:
X is —O— or —S—:
R′6 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7C(S)OR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R′17, R18 and R19 are each, independently, —H, —C(O)R22, or (alk)O(alk);
provided that at least one of R′17, R18, or R19 is not —H:
R22, for each occurrence is independently optionally substituted alkyl, optionally substituted aryl, —O(alk), amino, alkyl amino, or dialkyl amino;
alk is a lower alkyl;
X′ is —O—O— or —S—S—;
R′2 is —OH, —SH, or —NHR7:
R70 is —OH, —SH, or —NHR7:
R20 is C(O)Ry:
Ry is an optionally substituted alkyl;
X1 is O or S:
R71 and R72 are each, independently, —H, —C(O)R22, or (alk)O(alk);
R23 is —C(O)R22 or -alk-O—C(O)R22;
alk is a lower alkyl:
ring A is optionally further substituted with one or two independently selected substituents in addition to R3;
ring E is aromatic or non-aromatic;
X16 is —O—, —NR7—, or —S—:
Y is —(CR38R′39)k—, —C(O)—, —C(S)—, —C(NR8)—, —CR7═, —O—, —NR7—, —N═, or —S—;
Z′ is —(CR38R′39)k—, ═CR7—, —O—, —S—, —NR7—, ═N—, or —CR′40═CR′41—;
R100 id —OH, —SH, —NR7H, —OR′26, —SR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)7, or —SP(O)(OR7;
R′26, for each occurrence is, independently, a C1-C6 alkyl;
R38 and R′39, for each occurrence, are 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, an optionally substituted heteroaralkyl, halo, cyano, nitro, quanadino, a haloalkyl, a heteroalkyl, alkoxy, haloalkoxy, —NR10R11, —OR7, —C(O)R7, —C(O)OR7, —C(S)R7, —C(O)SR7, —C(S)SR7, —C(S)OR7, —C(S)NR10R11, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —OC(O)R7, —OC(O)OR7, —OC(S)OR7, —OC(NR8)OR7, —SC(O)R7, —SC(O)OR7, —SC(NR8)OR7, —OC(S)R7, —SC(S)R7, —SC(S)OR7, —OC(O)NR10R11, —OC(S)NR10R11, —OC(NR8)NR10R11, —SC(O)NR10R11, —SC(NR8)NR10R11, —SC(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —C(O)NR10R11, —NR8C(O)R7, —NR7C(S)R7, —NR7C(S)OR7, —NR7C(NR8)R7, —NR7C(O)OR7, —NR7C(NR8)OR7, —NR7C(O)NR10R11, —NR7C(S)NR10R11, —NR7C(NR8)NR10R11, —SR7, —S(O)pR7, —OS(O)pR7, —OS(O)pOR7, —OS(O)pNR10R11, S(O)pOR7, —NR8S(O)pR7, —NR7S(O)pNR10R11, —NR7S(O)pOR7, —S(O)pNR10R11, —SS(O)pR7, SS(O)pOR7, —SS(O)pNR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
or R38 and R′39 together with the carbon or carbon atoms to which they are attached form a three to eight membered cycloalkyl or a three to eight membered cycloalkenyl;
R′40 and R′41, for each occurrence, are, 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′40 and R′41, together with the carbon atoms to which they are attached form a three to eight membered cycloalkenyl;
k is 1 or 2;
provided that when R′5 is p-chlorophenyl, rings A and E together are not benzofuranyl:
ring F is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to R3:
ring G is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to -T1-V1-T2-V2;
R103 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R10, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)OH, —C(O)NHR8, —C(O)SH, —S(O)OH, —S(O)2OH, —S(O)NHR8, —S(O)2NHR8, —OP(O)(OR7)2 or —SP(O)(OR7)2;
T1 is absent or a C1-C4 alkylene:
T2 is absent or a C1-C4 alkylene, V1 is absent and V2 is —NRaRb, —NRaS(O), R**, —S(O)NRaRb, S(O)2NRaRb or C(O)NRaRb:
or
T2 is absent or a C1-C4 alkylene. V, is —O—, —S—, —N(R*)— or —C(O)N(R*)— and V2 is —S(O)NRaRb, —S(O)2NRaRb or —C(O)NRaRb;
or
T2 is a C2-C4 alkylene, V1 is —O—, —S, —N(R*)—, —C(O)O—, C(O)N(R*)— and V2 is —NRaRb, or —NRaS(O)2R**;
each R* is independently —H or C1-C3 alkyl:
each R** 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 heteroaralkyl:
Ra and Rb, for each occurrence, are 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 or heteroaryl, or an optionally substituted aralkyl:
or Ra and Rb, taken together with the nitrogen to which they are attached, form an optionally substituted heteroaryl or heterocyclyl:
wherein when T1, T2 and V1 are absent and V2 is —NRaRb then ring G is not phenyl, and when T1, T2 and V, are absent and V, is —C(O)NRaRb then ring G is not naphthyl or indolyl:
with the proviso that the compound is not
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-methoxy-phenyl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(naphthalen-1-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-phenyl-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(2,3-difluorophenyl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(quinolin-5-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(3-methyl-quinolin-5-yl)-5-carboxyamino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-(1-methyl-2-chloro-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-[3,5-di-(trifluoromethyl)-phenyl]-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-trifluoromethyl-Phenyl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-isopropylphenyl)-5-(thiocarboxyamino)-[1,2,4]triazole,
3-(2-Hydroxy-4-methoxymethyoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2-Hydroxy-4-(2-hydroxy-ethoxy)-phenyl]-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(naphthalen-1-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Dihydroxy-phenyl)-4-(naphthalen-1-yl)-5-(dimethylcarbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diethoxycarbonyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethoxycarbonylsulfanyl)-[1,2,4]triazole;
3-(2,4-Di-isobutyryloxy-phenyl)-4-(naphthalen-1-yl)-5-(isobutyrylsulfanyl)-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(quinolin-5-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-(acetylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-(2,4-Diethylcarbamoyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethylcarbamoylsulfanyl)-[1,2,4]triazole;
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.

90 more elements

A method of treating or preventing proliferative disorder in a mammal, comprising administering to the mammal an effective amount of a compound selected from the group consisting of:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
R1, R2, and R3 are each, independently, —OH, —SH, —NHR7, —OR26, —SR26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R5 is an optionally substituted alkyl:
an optionally substituted heteroaryl or an optionally substituted aryl;
R6 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7—SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R7 and R8, 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R26 is a lower alkyl;
p, for each occurrence, is independently, 1 or 2;
m, for each occurrence, is independently, 1, 2, 3 or 4;
R′1 is, —NHR7, —NHC(O)NR10R11, —NHC(O)R7, —NHC(O)OR7, —NHCH2C(O)R7, —NHCH2C(O)OR7, —NHCH2C(O)NR10R11, —NHS(O)pR7, —NHS(O)pNR10R11, —NHS(O)pOR7, —NHC(S)R7, —NHC(S)OR7, —NHC(S)NR10R11, —NHC(NR8)R7, —NHC(NR8)OR7, or —NHC(NR8)NR10R11;
R′3 is —OH, —SH, or —NHR7:
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
Z is a substituent;
t is 0, 1, 2, or 3;
X is —O— or —S—;
R′6 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7:
R′17, R18, and R19 are each, independently, —H, —C(O)R22, or (alk)O(alk);
provided that at least one of R′17, R18, or R19 is not —H;
R22, for each occurrence is independently optionally substituted alkyl, optionally substituted aryl, —O(alk), amino, alkyl amino, or dialkyl amino;
alk is a lower alkyl;
X′ is —O—O— or —S—S—;
R′2 is —OH, —SH, or —NHR7;
R70 is —OH, —SH, or —NHR7;
R20 is C(O)Ry;
Ry is an optionally substituted alkyl;
X1 is O or S;
R71 and R72 are each, independently, —H, —C(O)R22 or (alk)O(alk);
R23 is —C(O)R22 or -alk-O—C(O)R22;
alk is a lower alkyl;
ring A is optionally further substituted with one or two independently selected substituents in addition to R3:
ring E is aromatic or non-aromatic:
X16 is —O—,—NR7—, or —S—:
Y is —CR38R′39)k—, —C(O)—, —C(S)—, —C(NR8)—, —CR7═, —O—, —NR7—, —N═, or —S—;
Z′ is —(CR38R′39)k—, ═CR7—, —O—, —S—, —NR7—, ═N—, or —CR′40═CR′41—;
R100 id —OH, —SH, —NR7H, —OR′26, —SR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)9;
R′26, for each occurrence is, independently, a C1-C6 alkyl:
R38 and R′39, for each occurrence, are 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, an optionally substituted heteroaralkyl, halo, cyano, nitro, quanadino, a haloalkyl, a heteroalkyl, alkoxy, haloalkoxy, —NR10R11, —OR7, —C(O)R7, —C(O)OR7, —C(S)R7, —C(O)SR7, —C(S)SR7, —C(S)OR7, —C(S)NR10R11, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —OC(O)R7, —OC(O)OR7, —OC(S)OR7, —OC(NR8)OR7, —SC(O)R7, —SC(O)OR7, —SC(NR8)OR7, —OC(S)R7, —SC(S)R7, —SC(S)OR7, —OC(O)NR10R11, —OC(S)NR10R11, —OC(NR8)NR10R11, —SC(O)NR10R11, —SC(NR8)NR10R11, —SC(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —C(O)NR10R11, —NR8C(O)R7, —NR7C(S)R7, —NR7C(S)OR7, —NR7C(NR8)R7, —NR7C(O)OR7, —NR7C(NR8)OR7, —NR7C(O)NR10R11, —NR7C(S)NR10R11, —NR7C(NR8)NR10R11, —SR7, —S(O)pR7, —OS(O)pR7, —OS(O)pOR7, —OS(O)pNR10R11, —S(O)pOR7, —NR8S(O)pR7, —NR7S(O)pNR10R11, —NR7S(O)pOR7, —S(O)pNR10R11, —SS(O)pR7, —SS(O)pOR7, —SS(O)pNR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
or R38 and R′39 together with the carbon or carbon atoms to which they are attached form a three to eight membered cycloalkyl or a three to eight membered cycloalkenyl;
R′40 and R′41, for each occurrence, are, 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′40 and R′41, together with the carbon atoms to which they are attached form a three to eight membered cycloalkenyl:
k is 1 or 2;
provided that when R′5 is p-chlorophenyl, rings A and E together are not benzofuranyl:
ring F is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to R3;
ring G is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to -T1-V1-T2-V2;
R103 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26—O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)R7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)OH, —C(O)NHR8, —C(O)SH, —S(O)OH, —S(O)2OH, —S(O)NHR8, —S(O)2NHR8, —OP(O)(OR7)2 or —SP(O)(OR7)2;
T1 is absent or a C1-C4 alkylene:
T2 is absent or a C1-C4 alkylene, V1 is absent and V2 is —NRaRb, —NRaS(O)2R**, —S(O)NRaRb, S(O)2NRaRb or —C(O)NRaRb;
or
T2 is absent or a C1-C4 alkylene, V1 is —O—, —S—, —N(R*)— or —C(O)N(R*)— and V2 is —S(O)NRaRb, —S(O)2NRaRb or —C(O)NRaRb;
or
T2 is a C2-C4 alkylene. V1 is —O—, —S, —N(R*)—, —C(O)O—, C(O)N(R*)— and V2 is —NRaRb, or —NRaS(O)2R**;
each R* is independently —H or C1-C3 alkyl;
each R** 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 heteroaralkyl:
Ra and Rb, for each occurrence, are 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 or heteroaryl, or an optionally substituted aralkyl;
or Ra and Rb, taken together with the nitrogen to which they are attached, form an optionally substituted heteroaryl or heterocyclyl;
wherein when T1, T2 and V1 are absent and V2 is —NRaRb then ring G is not phenyl, and when T1, T2 and V1, are absent and V2 is —C(O)NRaRb then ring G is not naphthyl or indolyl:
with the proviso that the compound is not
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-methoxy-phenyl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(naphthalen-1-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-phenyl-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-Phenyl)-4-(2,3-difluorophenyl)-5-ureido-[1,2,4]triazole
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(quinolin-5-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(3-methyl-quinolin-5-yl)-5-carboxyamino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-(1-methyl-2-chloro-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-Phenyl)-4-[3,5-di-(trifluoromethyl)-phenyl]-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-Phenyl)-4-(3-trifluoromethyl-phenyl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-Phenyl)-4-(naphthalene-1-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-isopropylphenyl)-5-(thiocarboxyamino)-[1,2,4]triazole,
3-(2-Hydroxy-4-methoxymethyoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2-Hydroxy-4-(2-hydroxy-ethoxy)-phenyl]-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(naphthalen-1-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Dihydroxy-phenyl)-4-(naphthalen-1-yl)-5-(dimethylcarbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diethoxycarbonyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethoxycarbonylsulfanyl)-[1,2,4]triazole;
3-(2,4-Di-isobutyryloxy-phenyl)-4-(naphthalen-1-yl)-5-(isobutyrylsulfanyl)-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(quinolin-5-yl)-5-(dim carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-(acetylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-(2,4-Diethylcarbamoyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethylcarbamoylsulfanyl)-[1,2,4]triazole;
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.

91 more elements

A method of treating cancer in a mammal, comprising administering to the mammal an effective amount of a compound selected from the group consisting of:

or a tautomer, Pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
R1, R2, and R3 are each, independently, —OH, —SH, —NHR7, —OR26, —SR26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R5 is an optionally substituted alkyl;
an optionally substituted heteroaryl or an optionally substituted aryl;
R6 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)NR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R7 and R8, 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R26 is a lower alkyl:
p, for each occurrence, is independently, 1 or 2;
m, for each occurrence, is independently, 1, 2, 3 or 4;
R′1 is, —NHR7, —NHC(O)NR10R11, —NHC(O)R7, —NHC(O)OR7, —NHCH2C(O)R7, —NHCH2C(O)OR7, —NHCH2C(O)NR10R11, —NHS(O)pR7, —NHS(O)pNR10R11, —NHS(O)pOR7, —NHC(S)R7, —NHC(S)OR7, —NHC(S)NR10R11, —NHC(NR8)R7, —NHC(NR8)OR7, or —NHC(NR8)NR10R11;
R′3 is —OH, —SH, or —NHR7;
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
Z is a substituent;
t is 0, 1, 2, or 3;
X is —O— or —S—;
R′6 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)R7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)OR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R′17, R18 and R19 are each, independently, —H, —C(O)R22, or (alk)O(alk);
provided that at least one of R′17, R18, or R19 is not —H;
R22, for each occurrence is independently optionally substituted alkyl, optionally substituted aryl, —O(alk), amino, alkyl amino, or dialkyl amino;
alk is a lower alkyl;
X′ is —O—O— or —S—S—;
R′2 is —OH, —SH, or —NHR7;
R70 is —OH, —SH, or —NHR7;
R20 is C(O)Ry
Ry is an optionally substituted alkyl;
X1 is O or S:
R71 and R72 are each, independently, —H, —C(O)R22, or (alk)O(alk);
R23 is —C(O)R22 or -alk-O—C(O)R22;
alk is a lower alkyl;
ring A is optionally further substituted with one or two independently selected substituents in addition to R3;
ring E is aromatic or non-aromatic;
X16 is —O—, —NR7—, or —S—;
Y is —CR38R′39)k—, —C(O)—, —C(S)—, —C(NR8)—, —CR7═, —O—, —NR7—, —N═, or —S—;
Z′ is —CR38R′39)k—, ═CR7—, —O—, —S—, —NR7—, ═N—, or —CR′40═CR′41—;
R100 id —OH, —SH, —NR7H, —OR′26, —SR′26, —O(CH)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)OR7, —SC(O)R7, —NR7C(O)NR10R11, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pR7, —SS(O)pOR7, —NR7S(O)OR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R′26, for each occurrence is, independently, a C1-C6 alkyl;
R38 and R′39, for each occurrence, are 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, an optionally substituted heteroaralkyl, halo, cyano, nitro, quanadino, a haloalkyl, a heteroalkyl, alkoxy, haloalkoxy, —NR10R11, —OR7, —C(O)R7, —C(O)OR7, —C(S)R7, —C(O)SR7, —C(S)SR7, —C(S)OR7, —C(S)NR10R11, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —OC(O)R7, —OC(O)OR7, —OC(S)OR7, —OC(NR8)OR7, —SC(O)R7, —SC(O)OR7, —SC(NR8)OR7, —OC(S)R7, —SC(S)R7, —SC(S)OR7, —OC(O)NR10R11, —OC(S)NR10R11, —OC(NR8)NR10R11, —SC(O)NR10R11, —SC(NR8)NR10R11, —SC(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —C(O)NR10R11, —NR8C(O)R7, —NR7C(S)R7, —NR7C(S)OR7, —NR7C(NR8)R7, —NR7C(O)OR7, —NR7C(NR8)OR7, —NR7C(O)NR10R11, —NR7C(S)NR10R11, —NR7C(NR8)NR10R11, —SR7, —S(O)pR7, —OS(O)pR7, —OS(O)pOR7, —OS(O)pNR10R11, —S(O)pOR7, —NR8S(O)pR7, —NR7S(O)pNR10R11, —NR7S(O)pOR7, —S(O)pNR10R11, —SS(O)pR7, —SS(O)pOR7, —SS(O)pNR10R11, —OP(O)(OR7)2 or —SP(O)(OR7)2;
or R38 and R′39 together with the carbon or carbon atoms to which they are attached form a three to eight membered cycloalkyl or a three to eight membered cycloalkenyl;
R′40 and R′41, for each occurrence, are, 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′40 and R′41, together with the carbon atoms to which they are attached form a three to eight membered cycloalkenyl:
k is 1 or 2;
provided that when R′5 is p-chlorophenyl, rings A and E together are not benzofuranyl;
ring F is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to R3;
ring G is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to -T1-V1-T2-V2,
R103 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7—OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)OR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)OH, —C(O)NHR8, —C(O)SH, —S(O)OH, —S(O)2OH, —S(O)NHR8, —S(O)2NHR8, —OP(O)(OR7)2 or —SP(O)(OR7)2;
T2 is absent or a C1-C4 alkylene:
T2 is absent or a C1-C4 alkylene, V1 is absent and V2 is —NRaRb, —NRaS(O)2 R**, —S(O)NRaRb, —S(O)2NRaRb or —C(O)NRaRb;
or
T2 is absent or a C1-C4 alkylene, V1 is —O—, —S—, —N(R*)— or —C(O)N(R*)— and V2 is —S(O)NRaRb, S(O)2NRaRb or C(O)NRaRb;
or
T2 is a C2-C4 alkylene, V1 is —O—, —S, —N(R*)—, —C(O)O—, C(O)N(R*)— and V2 is —NRaRb, or —NRaS(O)2R**;
each R* is independently —H or C1-C3 alkyl:
each R** 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 heteroaralkyl:
Ra and Rb, for each occurrence, are 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 or heteroaryl, or an optionally substituted aralkyl;
or Ra and Rb, taken together with the nitrogen to which they are attached, form an optionally substituted heteroaryl or heterocyclyl:
wherein when T1, T2 and V1 are absent and V2 is —NRaRb then ring G is not phenyl, and when T1, T2 and V1 are absent and V2 is —C(O)NRaRb then ring G is not naphthyl or indolyl;
with the proviso that the compound is not
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-methoxy-phenyl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(naphthalen-1-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-phenyl-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(2,3-difluorophenyl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(quinolin-5-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(3-methyl-quinolin-5-yl)-5-carboxyamino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-(1-methyl-2-chloro-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-[3,5-di-(trifluoromethyl)-phenyl]-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-trifluoromethyl-phenyl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-isopropylphenyl)-5-(thiocarboxyamino)-[1,2,4]triazole,
3-(2-Hydroxy-4-methoxymethyoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2-Hydroxy-4-(2-hydroxy-ethoxy)-phenyl]-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(naphthalen-1-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Dihydroxy-phenyl)-4-(naphthalen-1-yl)-5-(dimethylcarbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diethoxycarbonyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethoxycarbonylsulfanyl)-[1,2,4]triazole;
3-(2,4-Di-isobutyryloxy-phenyl)-4-(naphthalen-1-yl)-5-(isobutyrylsulfanyl)-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(quinolin-5-yl)-5-(dim carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-(acetylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-(2,4-Diethylcarbamoyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethylcarbamoylsulfanyl)-[1,2,4]triazole;
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.

91 more elements

A method of treating or inhibiting angiogenesis in a subject in need thereof, comprising administering to the subject an effective amount of a compound selected from the group consisting of:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
R1, R2, and R3 are each, independently, —OH, —SH, —NHR7, —OR26, —SR26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R5 is an optionally substituted alkyl, an optionally substituted heteroaryl or an optionally substituted aryl:
R6 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11. —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)OR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, —S(O)pR7;
R7 and R8, 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R26 is a lower alkyl;
p, for each occurrence, is independently, 1 or 2:
m, for each occurrence, is independently, 1, 2, 3 or 4:
R′1 is, —NHR7, —NHC(O)NR10R11, —NHC(O)R7, —NHC(O)OR7, —NHCH2C(O)R7, —NHCH2C(O)OR7, —NHCH2C(O)NR10R11, —NHS(O)pR7, —NHS(O)pNR10R11, —NHS(O)pOR7, —NHC(S)R7, —NHC(S)OR7, —NHC(S)NR10R11, —NHC(NR8)R7, —NHC(NR8)OR7, or —NHC(NR8)NR10R11,
R′3 is —OH, —SH, or —NHR7;
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
Z is a substituent;
t is 0, 1, 2, or 3;
X is —O— or —S—:
R′6 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)OR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)OR7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R′17, R18, and R19 are each, independently, —H, —C(O)R22, or (alk)O(alk);
provided that at least one of R′17, R18, or R19 is not —H:
R22, for each occurrence is independently optionally substituted alkyl, optionally substituted aryl, —O(alk), amino, alkyl amino, or dialkyl amino;
alk is a lower alkyl;
X′ is —O—O— or —S—S—;
R′2 is —OH, —SH, or —NHR7;
R70 is —OH, —SH, or —NHR7;
R20 is C(O)Ry;
Ry is an optionally substituted alkyl;
X1 is O or S:
R71 and R72 are each, independently, —H, —C(O)R22, or (alk)O(alk);
R23 is —C(O)R22 or -alk-O—C(O)R22;
alk is a lower alkyl;
ring A is optionally further substituted with one or two independently selected substituents in addition to R3;
ring E is aromatic or non-aromatic;
X16 is —O—, —NR7—, or —S—;
Y is —(CR38R′39)k—, —C(O)—, —C(S)—, —C(NR8)—, —CR7═, —O—, —NR7—, —N═, or —S—;
Z′ is —(CR38R′39)k—, ═CR7—, —O—, —S—, —NR7—, ═N—, or —CR′40═CR′41—;
R100 id —OH, —SH, —NR7H, —OR′26, —SR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R′26 for each occurrence is, independently, a C1-C6 alkyl;
R38 and R′39, for each occurrence, are 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, an optionally substituted heteroaralkyl, halo, cyano, nitro, quanadino, a haloalkyl, a heteroalkyl, alkoxy, haloalkoxy, —NR10R11, —OR7, —C(O)R7, —C(O)OR7, —C(S)R7, —C(O)SR7, —C(S)SR7, —C(S)OR7, —C(S)NR10R11, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —OC(O)R7, —OC(O)OR7, —OC(S)OR7, —OC(NR8)OR7, —SC(O)R7, —SC(O)OR7, —SC(NR8)OR7, —OC(S)R7, —SC(S)R7, —SC(S)OR7, —OC(O)NR10R11, —OC(S)NR10R11, —OC(NR8)NR10R11, —SC(O)NR10R11, —SC(NR8)NR10R11, —SC(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —C(O)NR10R11, —NR8C(O)R7, —NR7C(S)R7, —NR7C(S)OR7, —NR7C(NR8)R7, —NR7C(O)OR7, —NR7C(NR8)OR7, —NR7C(O)NR10R11, —NR7C(S)NR10R11, —NR7C(NR8)NR10R11, —SR7, —S(O)pR7, —OS(O)pR7, —OS(O)pOR7, —OS(O)pNR10R11, —S(O)pOR7, —NR8S(O)pR7, —NR7S(O)pNR10R11, —NR7S(O)pOR7, —S(O)pNR10R11, —SS(O)pR7, —SS(O)pOR7, —SS(O)pNR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
or R38 and R′39 together with the carbon or carbon atoms to which they are attached form a three to eight membered cycloalkyl or a three to eight membered cycloalkenyl;
R′40 and R′41, for each occurrence, are, 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′40 and R′41, together with the carbon atoms to which they are attached form a three to eight membered cycloalkenyl;
k is 1 or 2;
provided that when R′5 is p-chlorophenyl, rings A and E together are not benzofuranyl;
ring F is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to R3;
ring G is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to -T1-V1-T2-V2;
R103 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)OH, —C(O)NHR8, —C(O)SH, —S(O)OH, —S(O)2OH, —S(O)NHR8, —S(O)2NHR8, —OP(O)(OR7)2 or —SP(O)(OR7)2;
T1 is absent or a C1-C4 alkylene:
T2 is absent or a C1-C4 alkylene, V1 is absent and V2 is —NRaRb, —NRaS(O)2R**, —S(O)NRaRb, S(O)2NRaRb or —C(O)NRaRb;
or
T2 is absent or a C1-C4 alkylene, V1 is —O—, —S—, —N(R*)— or —C(O)N(R*)— and V2 is —S(O)NRaRb, —S(O)2NRaRb or —C(O)NRaRb;
or
T2 is a C2-C4 alkylene, V1 is —O—, —S, —N(R*)—, —C(O)O—, C(O)N(R*)— and V2 is —NRaRb, or —NRaS(O)2R**;
each R* is independently —H or C1-C3 alkyl:
each R** 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 heteroaralkyl;
Ra and Rb, for each occurrence, are 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 or heteroaryl, or an optionally substituted aralkyl;
or Ra and Rb, taken together with the nitrogen to which they are attached, form an optionally substituted heteroaryl or heterocyclyl;
wherein when T1, T2 and V1 are absent and V1 is —NRaRb then ring G is not phenyl, and when T1, T2 and V1 are absent and V2 is —C(O)NRaRb then ring G is not naphthyl or indolyl:
with the proviso that the compound is not
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-methoxy-phenyl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(naphthalen-1-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-phenyl-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(2,3-difluorophenyl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(quinolin-5-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(3-methyl-quinolin-5-yl)-5-carboxyamino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-(1-methyl-2-chloro-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-Phenyl)-4-[3,5-di-(trifluoromethyl)-phenyl]-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-Phenyl)-4-(3-trifluoromethyl-phenyl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-isopropylphenyl)-5-(thiocarboxyamino)-[1,2,4]triazole,
3-(2-Hydroxy-4-methoxymethyoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2-Hydroxy-4-(2-hydroxy-ethoxy)-phenyl]-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(naphthalen-1-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Dihydroxy-phenyl)-4-(naphthalen-1-yl)-5-(dimethylcarbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diethoxycarbonyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethoxycarbonylsulfanyl)-[1,2,4]triazole;
3-(2,4-Di-isobutyryloxy-phenyl)-4-(naphthalen-1-yl)-5-(isobutyrylsulfanyl)-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(quinolin-5-yl)-5-(dim carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-(acetylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-(2,4-Diethylcarbamoyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethylcarbamoylsulfanyl)-[1,2,4]triazole;
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.

90 more elements

A method of treating or preventing an infection in a subject, comprising administering to the subject an effective amount of a compound selected from the group consisting of:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
R1, R2, and R3 are each, independently, —OH, —SH, —NHR7, —OR′26, —SR26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R5 is an optionally substituted alkyl;
an optionally substituted heteroaryl or an optionally substituted aryl;
R6 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R7 and R8, 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:
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R26 is a lower alkyl;
p, for each occurrence, is independently, 1 or 2;
m, for each occurrence, is independently, 1, 2, 3 or 4;
R′1 is, —NHR7, —NHC(O)NR10R11, —NHC(O)R7, —NHC(O)OR7, —NHCH2C(O)R7, —NHCH2C(O)OR7, —NHCH2C(O)NR10R11, —NHS(O)pR7, —NHS(O)pNR10R11, —NHS(O)pOR7, —NHC(S)R7, —NHC(S)OR7, —NHC(S)NR10R11, —NHC(NR8)R7, —NHC(NR8)OR7, or —NHC(NR8)NR10R11;
R′3 is —OH, —SH, or —NHR7;
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
Z is a substituent;
t is 0, 1, 2 or 3;
X is —O— or —S—;
R′6 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R10, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R′17, R18, and R19 are each, independently, —H, —C(O)R22 or (alk)O(alk);
provided that at least one of R′17, R18 or R19 is not —H;
R22, for each occurrence is independently optionally substituted alkyl, optionally substituted aryl, —O(alk), amino, alkyl amino, or dialkyl amino;
alk is a lower alkyl;
X′ is —O—O— or —S—S—;
R′2 is —OH, —SH, or —NHR7:
R70 is —OH, —SH, or —NHR7;
R20 is C(O)Ry;
Ry is an optionally substituted alkyl;
X2 is O or S;
R71 and R72 are each, independently, —H, —C(O)R22, or (alk)O(alk);
R23 is —C(O)R22 or -alk-O—C(O)R29;
alk is a lower alkyl;
ring A is optionally further substituted with one or two independently selected substituents in addition to R3;
ring E is aromatic or non-aromatic;
X16 is —O—, —NR7—, or —S—;
Y is —CR38R′39)k—, —C(O)—, —C(S)—, —C(NR8)—, —CR7═, —O—, —NR7—, —N═, or —S—;
Z′ is —(CR38R′39)k—, ═CR7—, —O—, —S—, —NR7—, ═N—, or —CR′40═CR′41—;
R100 id —OH, —SH, —NR7H, —OR′26, —SR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)2NR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R′26, for each occurrence is, independently, a C1-C6 alkyl;
R38 and R′39, for each occurrence, are 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, an optionally substituted heteroaralkyl, halo, cyano, nitro, quanadino, a haloalkyl, a heteroalkyl, alkoxy, haloalkoxy, —NR10R11, —OR7, —C(O)R7, —C(O)OR7, —C(S)R7, —C(O)SR7, —C(S)SR7, —C(S)OR7, —C(S)NR10R11, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —OC(O)R7, —OC(O)OR7, —OC(S)OR7, —OC(NR8)OR7, —SC(O)R7, —SC(O)OR7, —SC(NR8)OR7, —OC(S)R7, —SC(S)R7, —SC(S)OR7, —OC(O)NR10R11, —OC(S)NR10R11, —OC(NR8)NR10R11, —SC(O)NR10R11, —SC(NR8)NR10R11, —SC(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —C(O)NR10R11, —NR8C(O)R7, —NR7C(S)R7, —NR7C(S)OR7, —NR7C(NR8)R7, —NR7C(O)OR7, —NR7C(NR8)OR7, —NR7C(O)NR10R11, —NR7C(S)NR10R11, —NR7C(NR8)NR10R11, —SR7, —S(O)pR7, —OS(O)pR7, —OS(O)pOR7, —OS(O)pNR10R11, —S(O)pOR7, —NR8S(O)pR7, —NR7S(O)pNR10R11, —NR7S(O)pOR7, —S(O)pNR10R11, —SS(O)pR7, —SS(O)pR7, —SS(O)pNR10R11, —OP(O)(OR7)2 or —SP(O)(OR7)2;
or R38 and R′39 together with the carbon or carbon atoms to which they are attached form a three to eight membered cycloalkyl or a three to eight membered cycloalkenyl;
R′40 and R′41, for each occurrence, are, 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′40 and R′41, together with the carbon atoms to which they are attached form a three to eight membered cycloalkenyl;
k is 1 or 2;
provided that when R′5 is p-chlorophenyl, rings A and E together are not benzofuranyl;
ring F is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to R3;
ring G is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to -T1-V1-T2-V2;
R103 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)OH, —C(O)NHR8, —C(O)SH, —S(O)OH, —S(O)OH, —S(O)NHR8, —S(O)2NHR8, —OP(O)(OR7)2 or —SP(O)(OR7)2;
T1 is absent or a C1-C4 alkylene;
T2 is absent or a C1-C4 alkylene, V1 is absent and V2 is —NRaRb, —NRaS(O)2 R**, —S(O)NRaRb, —S(O)2NRaRb or —C(O)NRaRb;
or
T2 is absent or a C1-C4 alkylene, V, is —O—, —S—, —N(R*)— or —C(O)N(R*)— and V2 is —S(O)NRaRb, —S(O)NRaRb or —C(O)NRaRb or
T2 is a C2-C4 alkylene, V1 is —O—, —S, —N(R*)—, —C(O)O—, C(O)N(R*)— and V2 is —NRaRb, or —NRaS(O)2R**;
each R* is independently —H or C1-C3 alkyl:
each R** 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 heteroaralkyl;
Ra and Rb, for each occurrence, are 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 or heteroaryl, or an optionally substituted aralkyl;
or Ra and Rb, taken together with the nitrogen to which they are attached, form an optionally substituted heteroaryl or heterocyclyl;
wherein when T1, T2 and V1 are absent and V2 is —NRaRb then ring G is not phenyl, and when T1, T2 and V1 are absent and V1 is —C(O)NRaRb then ring G is not naphthyl or indolyl;
with the proviso that the compound is not
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-methoxy-phenyl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(naphthalen-1-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-phenyl-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(2,3-difluorophenyl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(quinolin-5-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(3-methyl-quinolin-5-yl)-5-carboxyamino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-(1-methyl-2-chloro-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-[3,5-di-(trifluoromethyl)-phenyl]-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-trifluoromethyl-phenyl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-isopropylphenyl)-5-(thiocarboxyamino)-[1,2,4]triazole,
3-(2-Hydroxy-4-methoxymethyoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2-Hydroxy-4-(2-hydroxy-ethoxy)-phenyl]-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(naphthalen-1-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole:
3-(2,4-Dihydroxy-phenyl)-4-(naphthalen-1-yl)-5-(dimethylcarbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diethoxycarbonyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethoxycarbonylsulfanyl)-[1,2,4]triazole;
3-(2,4-Di-isobutyryloxy-phenyl)-4-(naphthalen-1-yl)-5-(isobutyrylsulfanyl)-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(quinolin-5-yl)-5-(dim carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-(acetylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-(2,4-Diethylcarbamoyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethylcarbamoylsulfanyl)-[1,2,4]triazole;
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.

90 more elements

A method of treating or preventing an inflammatory disorder in a subject, comprising administering to the subject an effective amount of a compound selected from the group consisting of:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
R1, R2, and R3 are each, independently, —OH, —SH, —NHR7, —OR26, —SR26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)NR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R5 is an optionally substituted alkyl;
an optionally substituted heteroaryl or an optionally substituted aryl;
R6 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R7 and R8 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R26 is a lower alkyl;
p, for each occurrence, is independently, 1 or 2;
m, for each occurrence, is independently, 1, 2, 3 or 4:
R′1 is, —NHR7, —NHC(O)NR10R11, —NHC(O)R7, —NHC(O)OR7, —NHCH2C(O)R7, —NHCH2C(O)OR7, —NHCH2C(O)NR10R11, —NHS(O)pR7, —NHS(O)pNR10R11, —NHS(O)pOR7, —NHC(S)R7, —NHC(S)OR7, —NHC(S)NR10R11, —NHC(NR8)R7, —NHC(NR8)OR7, or —NHC(NR8)NR10R11;
R′3 is —OH, —SH, or —NHR7;
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
Z is a substituent;
t is 0, 1, 2, or 3;
X is —O— or —S—:
R′6 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R′17, R18, and R19 are each, independently, —H, —C(O)R22, or (alk)O(alk);
provided that at least one of R′17, R18, or R19 is not —H;
R22, for each occurrence is independently optionally substituted alkyl, optionally substituted aryl, —O(alk), amino, alkyl amino, or dialkyl amino;
alk is a lower alkyl;
X′ is —O—O— or —S—S—;
R′2 is —OH, —SH, or —NHR7;
R70 is —OH, —SH, or —NHR7;
R20 is C(O)Ry;
Ry is an optionally substituted alkyl;
X1 is O or S;
R71 and R72 are each, independently, —H, —C(O)R22, or (alk)O(alk);
R23 is —C(O)R22 or -alk-O—C(O)R22;
alk is a lower alkyl;
ring A is optionally further substituted with one or two independently selected substituents in addition to R3;
ring E is aromatic or non-aromatic;
X16 is —O—, —NR7—, or —S—:
Y is —(CR38R′39)k—, —C(O)—, —C(S)—, —C(NR8)—, —CR7═, —O—, —NR7—, —N═, or —S—;
Z′ is —CR38R′39)k—, ═CR7—, —O—, —S—, —NR7—, ═N—, or —CR′40═CR′41—;
R100 id —OH, —SH, —NR7H, —OR′26, —SR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R′26, for each occurrence is, independently, a C1-C6 alkyl;
R38 and R′39, for each occurrence, are 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, an optionally substituted heteroaralkyl, halo, cyano, nitro, quanadino, a haloalkyl, a heteroalkyl, alkoxy, haloalkoxy, —NR10R11, —OR7, —C(O)R7, —C(O)OR7, —C(S)R7, —C(O)SR7, —C(S)SR7, —C(S)OR7, —C(S)NR10R11, —C(NR8)R7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —OC(O)R7, —OC(O)OR7, —OC(S)OR7, —OC(NR8)OR7, —SC(O)R7, —SC(O)OR7, —SC(NR8)OR7, —OC(S)R7, —SC(S)R7, —SC(S)OR7, —OC(O)NR10R11, —OC(S)NR10R11, —OC(NR8)NR10R11, —SC(O)NR10R11, —SC(NR8)NR10R11, —SC(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —C(O)NR10R11, —NR8C(O)R7, —NR7C(S)R7, —NR7C(S)OR7, —NR7C(NR8)R7, —NR7C(O)OR7, —NR7C(NR8)OR7, —NR7C(O)NR10R11, —NR7C(S)NR10R11, —NR7C(NR8)NR10R11, —SR7, —S(O)pR7, —OS(O)pR7, —OS(O)pOR7, —OS(O)pNR10R11, —S(O)pOR7, —NR8S(O)pR7, —NR7S(O)pNR10R11, —NR7S(O)pOR7, —S(O)pNR10R11, —SS(O)pR7, —SS(O)pOR7, —SS(O)pNR10R11, —OP(O)(OR7)2 or —SP(O)(OR7)2;
or R38 and R′39 together with the carbon or carbon atoms to which they are attached form a three to eight membered cycloalkyl or a three to eight membered cycloalkenyl;
R′40 and R′41, for each occurrence, are, 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′40 and R′41, together with the carbon atoms to which they are attached form a three to eight membered cycloalkenyl;
k is 1 or 2;
provided that when R′5 is p-chlorophenyl, rings A and E together are not benzofuranyl;
ring F is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to R3;
ring G is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to -T1-V1-T2-V2
—R103 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26—O(CH2)mOH, —O(CH2)mSH, O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)NR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR10R11, —C(O)OH, —C(O)NHR8, —C(O)SH, —S(O)OH, —S(O)2OH, —S(O)NHR8, —S(O)2NHR8, —OP(O)(OR7)2 or —SP(O)(OR7)2;
T1 is absent or a C1-C4 alkylene;
T2 is absent or a C1-C4 alkylene, V1 is absent and V2 is —NRaRb, —NRaS(O)R**, —S(O)NRaRb, —S(O)2NRaRb or —C(O)NRaRb;
or
T2 is absent or a C1-C4 alkylene, V1 is —O—, —S—, —N(R*)— or —C(O)N(R*)— and V2 is —S(O)NRaRb, —S(O)2NRaRb or —C(O)NRaRb;
or
T2 is a C2-C4 alkylene. V1 is —O—, —S, —N(R*)—, —C(O)O—, C(O)N(R*)— and V2 is —NRaRb, or —NRaS(O)2R**;
each R′ is independently —H or C1-C3 alkyl;
each R** 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 heteroaralkyl;
Ra and Rb, for each occurrence, are 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 or heteroaryl, or an optionally substituted aralkyl;
or Ra and Rb, taken together with the nitrogen to which they are attached, form an optionally substituted heteroaryl or heterocyclyl;
wherein when T1, T2 and V1 are absent and V2 is —NRaRb then ring G is not phenyl, and when T1, T2 and V1 are absent and V2 is —C(O)NRaRb then ring G is not naphthyl or indolyl;
with the proviso that the compound is not
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-methoxy-phenyl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(naphthalen-1-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-phenyl-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(2,3-difluorophenyl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(quinolin-5-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(3-methyl-quinolin-5-yl)-5-carboxyamino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-(1-methyl-2-chloro-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-[3,5-di-(trifluoromethyl)-phenyl]-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-trifluoromethyl-phenyl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-(sulfamoylamino)-[1,2,4]triazole.
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-isopropylphenyl)-5-(thiocarboxyamino)-[1,2,4]triazole,
3-(2-Hydroxy-4-methoxymethyoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2-Hydroxy-4-(2-hydroxy-ethoxy)-phenyl]-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(naphthalen-1-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Dihydroxy-phenyl)-4-(naphthalen-1-yl)-5-(dimethylcarbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diethoxycarbonyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethoxycarbonylsulfanyl)-[1,2,4]triazole;
3-(2,4-Di-isobutyryloxy-phenyl)-4-(naphthalen-1-yl)-5-(isobutyrylsulfanyl)-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(quinolin-5-yl)-5-(dimethyl carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-(acetylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-(2,4-Diethylcarbamoyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethylcarbamoylsulfanyl)-[1,2,4]triazole;
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.

91 more elements

A method of treating or preventing an immune disorder in a subject, comprising administering to the subject an effective amount of a compound selected from the group consisting of:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
R1, R2, and R3 are each, independently, —OH, —SH, —NHR7, —OR26, —SR26, —O(CH2)mOH, O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R5 is an optionally substituted alkyl:
an optionally substituted heteroaryl or an optionally substituted aryl;
R6 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7—SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R7 and R8, 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;
R10 and R11, 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 R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R26 is a lower alkyl;
p, for each occurrence, is independently, 1 or 2;
m, for each occurrence, is independently, 1, 2, 3 or 4;
R′1 is, —NHR7, —NHC(O)NR10R11, —NHC(O)R7, —NHC(O)OR7, —NHCH2C(O)R7, —NHCH2C(O)OR7, —NHCH2C(O)N10R11, —NHS(O)pR7, —NHS(O)pNR10R11, —NHS(O)pOR7, —NHC(S)R7, —NHC(S)OR7, —NHC(S)NR10R11, —NHC(NR8)R7, —NHC(NR8)OR7, or —NHC(NR8)NR10R11,
R′3 is —OH, —SH, or —NHR7;
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
Z is a substituent;
t is 0, 1, 2, or 3;
X is —O— or —S—;
R′6 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)pNR10R11, or —S(O)pR7;
R′17, R18, and R19 are each, independently, —H, —C(O)R22, or (alk)O(alk);
provided that at least one of R′17, R18, or R19 is not —H;
R22, for each occurrence is independently optionally substituted alkyl, optionally substituted aryl, —O(alk), amino, alkyl amino, or dialkyl amino;
alk is a lower alkyl;
X′ is —O—O— or —S—S—;
R′2 is —OH, —SH, or —NHR7;
R70 is —OH, —SH, or —NHR7;
R20 is C(O)Ry;
Ry is an optionally substituted alkyl;
X1 is O or S;
R71 and R72 are each, independently, —H, —C(O)R22, or (alk)O(alk);
R23 is —C(O)R22 or -alk-O—C(O)R22;
alk is a lower alkyl;
ring A is optionally further substituted with one or two independently selected substituents in addition to R3;
ring E is aromatic or non-aromatic;
X16 is —O—, —NR7—, or —S—;
Y is —(CR38R′39)k—, —C(O)—, —C(S)—, —C(NR8)—, —CR7═, —O—, —NR7—, —N═, or —S—;
Z′ is —CR38R′39)k—, ═CR7—, —O—, —S—, —NR7—, ═N—, or —CR′40═CR′41—;
R100 id —OH, —SH, —NR7H, —OR′26, —SR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7—S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R′26, for each occurrence is, independently, a C1-C6 alkyl;
R38 and R′39, for each occurrence, are 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, an optionally substituted heteroaralkyl, halo, cyano, nitro, quanadino, a haloalkyl, a heteroalkyl, alkoxy, haloalkoxy, —NR10R11, —OR7, —C(O)R7, —C(O)OR7, —C(S)R7, —C(O)SR7, —C(S)SR7, —C(S)OR7, —C(S)NR10R11, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —OC(O)R7, —OC(O)OR7, —OC(S)OR7, —OC(NR8)OR7, —SC(O)R7, —SC(O)OR7, —SC(NR8)OR7, —OC(S)R7, —SC(S)R7, —SC(S)OR7, —OC(O)NR10R11, —OC(S)NR10R11, —OC(NR8)NR10R11, —SC(O)NR10R11, —SC(NR8)NR10R11, —SC(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —C(O)NR10R11, —NR8C(O)R7, —NR7C(S)R7, —NR7C(S)OR7, —NR7C(NR9)R7, —NR7C(O)OR7, —NR7C(NR8)OR7, —NR7C(O)NR10R11, —NR7C(S)NR10R11, —NR7C(NR8)NR10R11, —SR7, —S(O)pR7, —OS(O)pR7, —OS(O)pOR7, —OS(O)pNR10R11, —SS(O)pR7, —NR8S(O)pR7, —NR7S(O)pOR7, —S(O)pNR10R11, —SS(O)pR7, —SS(O)pOR7, —SS(O)pNR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
or R38 and R′39 together with the carbon or carbon atoms to which they are attached form a three to eight membered cycloalkyl or a three to eight membered cycloalkenyl;
R′40 and R′41, for each occurrence, are, 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′40 and R′41, together with the carbon atoms to which they are attached form a three to eight membered cycloalkenyl;
k is 1 or 2;
provided that when R′5 is p-chlorophenyl, rings A and E together are not benzofuranyl;
ring F is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to R3;
ring G is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to -T1-V1-T2-V2;
R103 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26 —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)OH, —C(O)NHR8, —C(O)SH, —S(O)OH, —S(O)2OH, —S(O)NHR8, —S(O)2NHR8, —OP(O)(OR7)2 or —SP(O)(OR7)2;
T1 is absent or a C1-C4 alkylene;
T2 is absent or a C1-C4 alkylene, V1 is absent and V2 is —NRaRb, NRaS(O)R2 R**, —S(O)NRaRb, —S(O)2NRaRb or —C(O)NRaRb;
or
T2 is absent or a C1-C4 alkylene, V1 is —O—, —S—, —N(R*)— or —C(O)N(R*)— and V2 is —S(O)NRaRb, —S(O)NRaRb or —C(O)NRaRb;
or
T2 is a C2-C4 alkylene. V1 is —O—, —S, —N(R*)—, —C(O)O—, C(O)N(R*)— and V2 is —NRaRb, or NRaS(O)2R**;
each R* is independently —H or C1-C3 alkyl,
each R** 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 heteroaralkyl;
Ra and Rb, for each occurrence, are 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 or heteroaryl, or an optionally substituted aralkyl;
or Ra and Rb, taken together with the nitrogen to which they are attached, form an optionally substituted heteroaryl or heterocyclyl;
wherein when T1, T2 and V1 are absent and V2 is —NRaRb then ring G is not phenyl, and when T1, T2 and V1 are absent and V2 is —C(O)NRaRb then ring G is not naphthyl or indolyl;
with the proviso that the compound is not
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-methoxy-phenyl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(naphthalen-1-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-phenyl-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(2,3-difluorophenyl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(quinolin-5-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(3-methyl-quinolin-5-yl)-5-carboxyamino-[1,2,4]triazole,
3-(2,4-Dihydroxy-Phenyl)-4-(1-methyl-2-chloro-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-[3,5-di-(trifluoromethyl)-phenyl]-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-trifluoromethyl-phenyl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-isopropylphenyl)-5-(thiocarboxyamino)-[1,2,4]triazole,
3-(2-Hydroxy-4-methoxymethyoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2-Hydroxy-4-(2-hydroxy-ethoxy)-phenyl]-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(naphthalen-1-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Dihydroxy-phenyl)-4-(naphthalen-1-yl)-5-(dimethylcarbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diethoxycarbonyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethoxycarbonylsulfanyl)-[1,2,4]triazole;
3-(2,4-Di-isobutyryloxy-phenyl)-4-(naphthalen-1-yl)-5-(isobutyrylsulfanyl)-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(quinolin-5-yl)-5-(dim carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-(acetylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-(2,4-Diethylcarbamoyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethylcarbamoylsulfanyl)-[1,2,4]triazole;
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.

91 more elements

A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound selected from the group consisting of:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:
R1, R2, and R3 are each, independently, —OH, —SH, —NHR7, —OR26, —SR26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7), or —SP(O)(OR7)2;
R5 is an optionally substituted alkyl;
an optionally substituted heteroaryl or an optionally substituted aryl;
R6 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)OR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pOR7, —S(O)NR10R11, or —S(O)pR7;
R7 and R8, 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;
R10 and R11, 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 R10 and R11 taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
R26 is a lower alkyl;
p, for each occurrence, is independently, 1 or 2;
m, for each occurrence, is independently, 1, 2, 3 or 4:
R′1 is, —NHR7, —NHC(O)NR10R11, —NHC(O)R7, —NHC(O)OR7, —NHCH2C(O)R7, —NHCH2C(O)OR7, —NHCH2C(O)NR10R11, —NHS(O)pR7, —NHS(O)pNR10R11, —NHS(O)pOR7, —NHC(S)R7, —NHC(S)OR7, —NHC(S)NR10R11, —NHC(NR8)R7, —NHC(NR8)OR7, or —NHC(NR8)NR10R11;
R′3 is —OH, —SH, or —NHR7;
R′5 is an optionally substituted heteroaryl or an optionally substituted aryl;
Z is a substituent;
t is 0, 1, 2, or 3;
X is —O— or —S—;
R′6 is —H, 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, —OR7, —SR7, —NR10R11, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7—SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)R7, —C(O)OR7, —C(O)NR10R11, —C(O)SR7, —C(S)R7, —C(S)OR7, —C(S)NR10R11, —C(S)SR7, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —S(O)pR7,
R′17, R18, and R19 are each, independently, —H, —C(O)R22, or (alk)O(alk);
provided that at least one of R′17 R18 or R19 is not —H;
R22, for each occurrence is independently optionally substituted alkyl, optionally substituted aryl, —O(alk), amino, alkyl amino, or dialkyl amino;
alk is a lower alkyl;
X′ is —O—O— or —S—S—;
R′2 is —OH, —SH, or —NHR7;
R70 is —OH, —SH, or —NHR7;
R20 is C(O)Ry;
Ry is an optionally substituted alkyl;
X1 is O or S;
R71 and R72 are each, independently, —H, —C(O)R22, or (alk)O(alk);
R23 is —C(O)R22 or -alk-O—C(O)R22;
alk is a lower alkyl;
ring A is optionally further substituted with one or two independently selected substituents in addition to R3;
ring E is aromatic or non-aromatic;
X16 is —O—, —NR7—, or —S—;
Y is —(CR38R′39)k—, —C(O)—, —C(S)—, —C(NR8)—, —CR7═, —O—, —NR7—, —N═, or —S—;
Z′ is —(CR38R′39)k—, ═CR7—, —O—, —S—, —NR7—, ═N—, or —CR′40═CR′41—;
R100 id —OH, —SH, —NR7H, —OR′26, —SR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7—OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
R′26, for each occurrence is, independently, a C1-C6 alkyl;
R38 and R′39, for each occurrence, are 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, an optionally substituted heteroaralkyl, halo, cyano, nitro, quanadino, a haloalkyl, a heteroalkyl, alkoxy, haloalkoxy, —NR10R11, —OR7, —C(O)R7, —C(O)OR7, —C(S)R7, —C(O)SR7, —C(S)SR7, —C(S)OR7, —C(S)NR10R11, —C(NR8)OR7, —C(NR8)R7, —C(NR8)NR10R11, —C(NR8)SR7, —OC(O)R7, —OC(O)OR7, —OC(S)OR7, —OC(NR8)OR7, —SC(O)R7, —SC(O)OR7, —SC(NR8)OR7, —OC(S)R7, —SC(S)R7, —SC(S)OR7, —OC(O)NR10R11, —OC(S)NR10R11, —OC(NR8)NR10R11, —SC(O)NR10R11, —SC(NR8)NR10R11, —SC(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —C(O)NR10R11, —NR8C(O)R7, —NR7C(S)R7, —NR7C(S)OR7, —NR7C(NR8)R7, —NR7C(O)OR7, —NR7C(NR8)OR7, —NR7C(O)NR10R11, —NR7C(S)NR10R11, —NR7C(NR8)NR10R11, —SR7, —S(O)pR7, —OS(O)pR7, —OS(O)pOR7, —OS(O)pNR10R11, —S(O)pOR7, —NR8S(O)pR7, —NR7S(O)pNR10R11, —NR7S(O)pOR7, —S(O)pNR10R11, —SS(O)pR7, —SS(O)pOR7, —SS(O)pNR10R11, —OP(O)(OR7)2, or —SP(O)(OR7)2;
or R38 and R′39 together with the carbon or carbon atoms to which they are attached form a three to eight membered cycloalkyl or a three to eight membered cycloalkenyl;
R′40 and R′41, for each occurrence, are, 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′40 and R′41, together with the carbon atoms to which they are attached form a three to eight membered cycloalkenyl;
k is 1 or 2;
provided that when R′5 is p-chlorophenyl, rings A and E together are not benzofuranyl;
ring F is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to R3;
ring G is an aryl or a heteroaryl, wherein the aryl or the heteroaryl are optionally further substituted with one or more substituents in addition to -T1-V1-T2-V2;
R103 is —OH, —SH, —NR7H, —OR′26, —SR′26, —NHR′26, —O(CH2)mOH, —O(CH2)mSH, —O(CH2)mNR7H, —S(CH2)mOH, —S(CH2)mSH, —S(CH2)mNR7H, —OC(O)NR10R11, —SC(O)NR10R11, —NR7C(O)NR10R11, —OC(O)R7, —SC(O)R7, —NR7C(O)R7, —OC(O)OR7, —SC(O)OR7, —NR7C(O)OR7, —OCH2C(O)R7, —SCH2C(O)R7, —NR7CH2C(O)R7, —OCH2C(O)OR7, —SCH2C(O)OR7, —NR7CH2C(O)OR7, —OCH2C(O)NR10R11, —SCH2C(O)NR10R11, —NR7CH2C(O)NR10R11, —OS(O)pR7, —SS(O)pR7, —S(O)pOR7, —NR7S(O)pR7, —OS(O)pNR10R11, —SS(O)pNR10R11, —NR7S(O)pNR10R11, —OS(O)pOR7, —SS(O)pOR7, —NR7S(O)pOR7, —OC(S)R7, —SC(S)R7, —NR7C(S)R7, —OC(S)OR7, —SC(S)OR7, —NR7C(S)OR7, —OC(S)NR10R11, —SC(S)NR10R11, —NR7C(S)NR10R11, —OC(NR8)R7, —SC(NR8)R7, —NR7C(NR8)R7, —OC(NR8)OR7, —SC(NR8)OR7, —NR7C(NR8)OR7, —OC(NR8)NR10R11, —SC(NR8)NR10R11, —NR7C(NR8)NR10R11, —C(O)OH, —C(O)NHR8, —C(O)SH, —S(O)OH, —S(O)2OH, —S(O)NHR8, —S(O)2NHR8, —OP(O)(OR7)2 or —SP(O)(OR7)2;
T1 is absent or a C1-C4 alkylene;
T2 is absent or a C1-C4 alkylene, V1 is absent and V2 is —NRaRb, —NRaS(O)2R**, —S(O)NRaRb, S(O)2NRaRb or —C(O)NRaRb;
or
T2 is absent or a C1-C4 alkylene, V1 is —O—, —S—, —N(R*)— or —C(O)N(R*)— and V2 is —S(O)NRaRb, —S(O)2NRaRb or —C(O)NRaRb;
or
T2 is a C2-C4 alkylene, V1 is —O—, —S, —N(R*)—, —C(O)O—, C(O)N(R*)— and V1 is —NRaRb, or —NRaS(O)2R**;
each R* is independently —H or C1-C3 alkyl;
each R** 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 heteroaralkyl;
Ra and Rb, for each occurrence, are 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 or heteroaryl, or an optionally substituted aralkyl;
or Ra and Rb, taken together with the nitrogen to which they are attached, form an optionally substituted heteroaryl or heterocyclyl;
wherein when T1, T2 and V1 are absent and V2 is —NRaRb then ring G is not phenyl, and when T1, T2 and V1 are absent and V2 is —C(O)NRaRb then ring G is not naphthyl or indolyl;
with the proviso that the compound is not
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-amino-[1,2,4]triazole
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-methoxy-phenyl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(naphthalen-1-yl)-5-amino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-phenyl-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(2,3-difluorophenyl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-isopropyl-indol-4-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(quinolin-5-yl)-5-ureido-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(3-methyl-quinolin-5-yl)-5-carboxyamino-[1,2,4]triazole,
3-(2,4-Dihydroxy-phenyl)-4-(1-methyl-2-chloro-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-[3,5-di-(trifluoromethyl)-phenyl]-5-carbamoyloxy-[1,2,4]triazole.
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-trifluoromethyl-phenyl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(naphthalene-1-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-(sulfamoylamino)-[1,2,4]triazole,
3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(3-isopropylphenyl)-5-(thiocarboxyamino)-[1,2,4]triazole,
3-(2-Hydroxy-4-methoxymethyoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2-Hydroxy-4-(2-hydroxy-ethoxy)-phenyl]-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(naphthalen-1-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole:
3-(2,4-Dihydroxy-phenyl)-4-(naphthalen-1-yl)-5-(dimethylcarbamoylsulfanyl)-[1,2,4]triazole:
3-(2,4-Diethoxycarbonyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethoxycarbonylsulfanyl)-[1,2,4]triazole:
3-(2,4-Di-isobutyryloxy-phenyl)-4-(naphthalen-1-yl)-5-(isobutyrylsulfanyl)-[1,2,4]triazole;
3-[2,4-Di-(dimethyl-carbamoyloxy)-phenyl]-4-(quinolin-5-yl)-5-(dimethyl-carbamoylsulfanyl)-[1,2,4]triazole;
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-(acetylsulfanyl)-[1,2,4]triazole:
3-(2,4-Diacetoxy-phenyl)-4-(naphthalen-1-yl)-5-mercapto-[1,2,4]triazole;
3-(2,4-Diethylcarbamoyloxy-phenyl)-4-(naphthalen-1-yl)-5-(ethylcarbamoylsulfanyl)-[1,2,4]triazole:
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.

91 more elements

Triazole compounds that modulate Hsp90 activity

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Triazole compounds that modulate Hsp90 activity

Life of this patent

Abstract

Claims69