Hydrazonamide compounds that modulate Hsp90 activity

A compound according to the formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —C(O)R7, —C(O)NR10R11, —C(O)OR7, —C(S)R7, —C(O)SR7, —C(S)SR7, —C(S)OR7, —C(S)NR10R11, —C(NR7)OR7, —C(NR7)R7, —C(NR7)NR10R11 or —C(NR7)SR7, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl represented by R1 are optionally and independently substituted;
• R2 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl, halo, cyano, nitro, —NR10R11, —OR7, —C(S)R7, —C(O)SR7, —C(S)SR7, —C(S)OR7, —C(S)NR10R11, —C(NR7)OR7, —C(NR7)NR10R11, —C(NR7)SR7, —OC(O)R7, —OC(O)OR7, —OC(S)OR7, —OC(NR7)OR7, —SC(O)R7, —SC(O)OR7, —SC(NR7)OR7, —OC(S)R7, —SC(S)R7, —SC(S)OR7, —OC(O)NR10R11, —OC(S)NR10R11, —OC(NR7)NR10R11, —SC(O)NR10R11, —SC(NR7)NR10R11, —SC(S)NR10R11, —OC(NR7)R7, —SC(NR7)R7, —NR7C(O)R7, —NR7C(S)R7, —NR7C(S)OR7, —NR7C(NR7)R7, —NR7C(O)OR7, —NR7C(NR7)OR7, —NR7C(O)NR10R11, —NR7C(S)NR10R11, —NR7C(NR7)NR10R11, —S(O)PR7, —OS(O)PR7, —OS(O)POR7, —OS(O)pNR10R11, —S(O)POR7, —NR7S(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, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl represented by R2 are optionally and independently substituted;
• R3 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR7, —C(O)R7, —C(O)OR7, —C(S)OR7, —C(O)NR10R11, —S(O)PR7, —C(S)R7 and —C(S)NR10R11, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl and heteroaralkyl represented by R3 is independently and optionally substituted;
• R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, aralkyl, heteroaralkyl, —OR7, —C(O)R7, —C(O)OR7, —C(S)OR7, —C(O)NR10R11, —S(O)PR7—C(S)R7 and —C(S)NR10R11, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, aralkyl and heteroaralkyl represented by R4 is independently and optionally substituted;
• each R7 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl, or heteraralkyl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl, and heteraralkyl represented by R7 is optionally and independently substituted;
• each R10 and R11 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl, or heteraralkyl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl, and heteraralkyl represented by R10 or R11 is optionally and independently substituted;
• or
• R10 and R11, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• Z is NH or O;
• Y is NR10;
• and
• each p is independently 0, 1 or 2;
• with the provisos that 1) when Z is O, then R3 is other than hydrogen;
• 2) when Z is NH, then R3 is other than an unsubstituted phenyl or a di-nitro substituted phenyl;
• or 3) when Z is NH and R3 is hydrogen, then R4 is not 1-methyl-indol-5-yl.