Macrocycles and uses thereof

A compound having the structure:

• wherein the dotted line - - - represents an optional bond, such that either a single or a double bond is present;
• R1 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or N(RA)2, wherein each occurrence of RA is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R2 is hydrogen, halogen, cyano, —ORB, —N(RB)2, —SRB, —O(C═O)RB, —N(RB)(C═O)(RB), —C(O)RB, —C(O)ORB, —CON(RB)2, —OCO2RB, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RB is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R3 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or —N(RC)2, wherein each occurrence of RC is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R4 is hydrogen, halogen, cyano, —ORD, —N(RD)2, —SRD, —O(C═O)RD, —N(RD)(C═O)(RD), —C(O)RD, —C(O)ORD, —CON(RD)2, —OCO2RD, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RD is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• Z is O;
• X is O;
• A and B together represent
• —CHR5—CHR6—, —CR5═CR6—, wherein R5 and R6 are each independently hydrogen, halogen, cyano, —ORJ, —N(RJ)2, —SRJ, —O(C═O)RJ, —O(S═O)RJ, —N(RJ)(C═O)(RJ), —C(═O)RJ, —C(═O)ORJ, —CON(RJ)2, —OCO2RJ, —OSO2RJ, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, and wherein R7 is hydrogen, —ORK, —SRK, —C(O)ORK, —S(O)2RK, —O(C═O)RK, —N(RK)(C═O)(RK), —C(O)RK, —C(O)ORK, —CON(RK)2, —OCO2RK, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RK is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or when A and B together represent —CHR5—CHR6—, R5 and R6 taken together represent a substituted or unsubstituted 3–7 membered aliphatic, heteroaliphatic, aryl or heteroaryl ring,
• D and E together represent —CHR8—CHR9—, —CR8═CR9—, wherein R8 and R9 are each independently hydrogen or lower alkyl;
• G and J together represent —CHR10—CHR11—, —CR10═CR11—, wherein R10 and R11 are each independently hydrogen or lower alkyl;
• K and L together represent C═O, C═S, CH—CH3, CH—CH(RL)2, C═C(RL)2, —CH2—, —C(—S(CH2)3S—)—, CH—ORL, CH—SRL, CH—N(RL)2, CH—N(RL)(C═O)(RL), C═N—O—RL, CH—N═O, C═C(RL)—N(RL)2, C═N—RL, C═N—N(RL)2, or, if the dotted line - - - represents a bond, whereby a double bond is present, then K and L together represent C—N(RL)2, wherein each occurrence of RL is independently hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or two occurrences of RL taken together represent a 3 to 7-membered cyclic aliphatic, heteroaliphatic, aromatic or heteroaromatic moiety;
• whereby each of the foregoing aliphatic and heteroaliphatic moieties may independently be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and each aryl, heteroaryl, alkylaryl, and alkylheteroaryl moiety may be substituted or unsubstituted;
• wherein one or any two of R1, RA, R2, RB, R3, RC, R4, RD, R5, R6, RJ, or RL are a linker covalently bonded to a compound selected from the group consisting of radicicol, monocillin, geldanamycin, and steroids wherein the linker is an aliphatic or heteroaliphatic moiety, whereby said aliphatic or heteroaliphatic moiety is substituted or unsubstituted, branched or unbranched, or cyclic or acyclic;
• and
• pharmaceutically acceptable derivatives thereof,
• with the proviso that:
• (1) if A and B together are
• and R5 and R6 are each hydrogen;
• if D and E together are —CH═CH—;
• if G and J together are —CH═CH—;
• if K and L together are C═O;
• if R1 is hydrogen or Cl;
• and if R3 is hydrogen,
• then R2 is not —ORB or —O(C═O)RB, wherein RB is hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• and R4 is not —ORD or —O(C═O)RD, wherein RD is hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• (2) if A and B together are
• and R5 and R6 are each hydrogen;
• if D and E together are —CH2—CH2—;
• if G and J together are —CH2—CH2—;
• if K and L together are C═O;
• if R1 is Cl;
• and if R3 is hydrogen,
• then R2 is not —ORB or —O(C═O)RB, wherein RB is hydrogen or an alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, aryl, aryloxy, heterocycle, cycloalkyl, cycloalkenyl, or cycloalkenyl fused to an aryl group;
• and R4 is not —ORD or —O(C═O)RD, wherein RD is hydrogen or an alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, aryl, aryloxy, heterocycle, cycloalkyl, cycloalkenyl, or cycloalkenyl fused to an aryl group;
• (3) if R1 is Cl;
• if R2 is ORB and RB is hydrogen, alkanoyl, alkenoyl, tert-butyl dimethylsilyl or tert-butyldiphenylsilyl;
• if R3 is hydrogen;
• if R4 is ORD and RD is hydrogen, alkanoyl, alkenoyl, tert-butyldimethylsilyl, or tert-butyldiphenylsilyl;
• if D and E together are —CH═CH—;
• if G and J together are —CH═CH—;
• if A and B together are
• or if A and B together are —CHR5—CHR6— and R6 is halogen and R5 is ORJ, wherein RJ is hydrogen, alkanoyl, or alkenoyl, or R5 is —O(S═O)RJ, wherein RJ is a second compound of formula (I) linked via an oxygen atom present at R5 in the second compound of formula (I), and wherein R6 of the second compound of formula (I) is halogen;
• Z of the second compound of formula (I) is O;
• X of the second compound of formula (I) is O, R1 of the second compound of formula (I) is Cl;
• R2 of the second compound of formula (I) is ORB and RB is hydrogen, alkanoyl, alkenoyl, tert-butyl dimethylsilyl or tert-butyldiphenylsilyl;
• R3 of the second compound of formula (I) is hydrogen;
• R4 of the second compound of formula (I) is ORD and RD is hydrogen, alkanoyl, alkenoyl, tert-butyldimethylsilyl, or tert-butyldiphenylsilyl;
• then K and L together are not C═O or C═N—O—RL, when RL is hydrogen, or substituted or unsubstituted lower alkyl, a substituted or unsubstituted alkenyl moiety, a substituted acyl moiety or a substituted or unsubstituted aryl moiety;
• except that K and L together can be C═N—O—RL, when RL is a linker covalently bonded to a compound selected from the group consisting of radicicol, monocillin, geldanamycin, and steroids.

A compound having the structure:

• wherein the dotted line - - - represents an optional bond, such that either a single or a double bond is present;
• R1 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or N(RA)2, wherein each occurrence of RA is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R2 is hydrogen, halogen, cyano, —ORB, —N(RB)2, —SRB, —O(C═O)RB, —N(RB)(C═O)(RB), —C(O)RB, —C(O)ORB, —CON(RB)2, —OCO2RB, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RB is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R3 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or —N(RC)2, wherein each occurrence of RC is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R4 is hydrogen, halogen, cyano, —ORD, —N(RD)2, —SRD, —O(C═O)RD, —N(RD)(C═O)(RD), —C(O)RD, —C(O)ORD, —CON(RD)2, —OCO2RD, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RD is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• Z is O;
• X is O;
• D and E together represent —CHR8—CHR9—, —CR8═CR9—, wherein R8 and R9 are each independently hydrogen or lower alkyl;
• G and J together represent —CHR10—CHR11—, —CR10═CR11—, wherein R10 and R11 are each independently hydrogen or lower alkyl;
• K and L together represent C═O, C═S, CH—CH3, CH—CH(RL)2, C═C(RL)2, —CH2—, —C(—S(CH2)3S—)—, CH—ORL, CH—SRL, CH—N(RL)2, CH—N(RL)(C═O)(RL), C═N—O—RL, CH—N═O, C═C(RL)—N(RL)2, C═N—RL, C═N—N(RL)2, or, if the dotted line - - - represents a bond, whereby a double bond is present, then K and L together represent C—N(RL,)2, wherein each occurrence of RL is independently hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or two occurrences of RL taken together represent a 3 to 7-membered cyclic aliphatic, heteroaliphatic, aromatic or heteroaromatic moiety;
• whereby each of the foregoing aliphatic and heteroaliphatic moieties may independently be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and each aryl, heteroaryl, alkylaryl, and alkylheteroaryl moiety may be substituted or unsubstituted;
• wherein one or any two of R1, RA, R2, RB, R3, RC, R4, RD, or RL are optionally a linker covalently bonded to a compound selected from the group consisting of radicicol, monocillin, geldanamycin, and steroids;
• and
• pharmaceutically acceptable derivatives thereof.

A compound having the structure:

• wherein the dotted line - - - represents an optional bond, such that either a single or a double bond is present;
• R1 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or N(RA)2, wherein each occurrence of RA is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R2 is hydrogen, halogen, cyano, —ORB, —N(RB)2, —SRB, —O(C═O)RB, —N(RB)(C═O)(RB), —C(O)RB, —C(O)ORB, —CON(RB)2, —OCO2RB, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RB is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R3 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or —N(RC)2, wherein each occurrence of RC is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R4 is hydrogen, halogen, cyano, —ORD, —N(RD)2, —SRD, —O(C═O)RD, —N(RD)(C═O)(RD), —C(O)RD, —C(O)ORD, —CON(RD)2, —OCO2RD, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RD is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• Z is O;
• X is O R7 is hydrogen, —ORK, —SRK, —C(O)ORK, —S(O)2RK, —O(C═O)RK, —N(RK)(C═O)(RK), —C(O)RK, —CON(RK)2, —OCO2RK, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RK is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• D and E together represent —CHR8—CHR9—, —CR8═CR9—, wherein R8 and R9 are each independently hydrogen or lower alkyl;
• G and J together represent —CHR10—CHR11—, —CR10═CR11—, wherein R10 and R11 are each independently hydrogen or lower alkyl;
• K and L together represent C═O, C═S, CH—CH3, CH—CH(RL)2, C═C(RL)2, —CH2—, —C(—S(CH2)3S—)—, CH—ORL, CH—SRL, CH—N(RL)2, CH—N(RL)(C═O)(RL), C═N—O—RL, CH—N═O, C═C(RL)—N(RL)2, C═N—RL, C═N—N(RL)2, or, if the dotted line - - - represents a bond, whereby a double bond is present, then K and L together represent C—N(RL)2, wherein each occurrence of RL is independently hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or two occurrences of RL taken together represent a 3 to 7-membered cyclic aliphatic, heteroaliphatic, aromatic or heteroaromatic moiety;
• whereby each of the foregoing aliphatic and heteroaliphatic moieties may independently be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and each aryl, heteroaryl, alkylaryl, and alkylheteroaryl moiety may be substituted or unsubstituted;
• wherein one or any two of R1, RA, R2, RB, R3, RC, R4, RD, or RL are optionally a linker covalently bonded to a compound selected from the group consisting of radicicol, monocillin, geldanamycin, and steroids;
• and
• pharmaceutically acceptable derivatives thereof.

A compound having the structure:

• wherein R1 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or N(RA)2, wherein each occurrence of RA is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R2 is hydrogen, halogen, cyano, —ORB, —N(RB)2, —SRB, —O(C═O)RB, —N(RB)(C═O)(RB), —C(O)RB, —C(O)ORB, —CON(RB)2, —OCO2RB, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RB is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R3 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or —N(RC)2, wherein each occurrence of RC is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R4 is hydrogen, halogen, cyano, —ORD, —N(RD)2, —SRD, —O(C═O)RD, —N(RD)(C═O)(RD), —C(O)RD, —C(O)ORD, —CON(RD)2, —OCO2RD, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RD is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• Z is O;
• X is O;
• A and B together represent
• —CHR5—CHR6—, —CR5═CR6—, wherein R5 and R6 are each independently hydrogen, halogen, cyano, —ORJ, —N(RJ)2, —SRJ, —O(C═O)RJ, —O(S═O)RJ, —N(RJ)(C═O)(RJ), —C(═O)RJ, —C(═O)ORJ, —CON(RJ)2, —OCO2RJ, —OSO2RJ, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, and wherein R7 is hydrogen, —ORK, —SRK, —C(O)ORK, —S(O)2RK, —O(C═O)RK, —N(RK)(C═O)(RK), —C(O)RK, —C(O)ORK, —CON(RK)2, —OCO2RK, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RK is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or when A and B together represent —CHR5—CHR6—, R5 and R6 taken together represent a substituted or unsubstituted 3–7 membered aliphatic, heteroaliphatic, aryl or heteroaryl ring,
• D and E together represent —CHR8—CHR9—, —CR8═CR9—, wherein R8 and R9 are each independently hydrogen or lower alkyl;
• G and J together represent —CHR10—CHR11—, —CR10═CR11—, wherein R10 and R11 are each independently hydrogen or lower alkyl;
• whereby each of the foregoing aliphatic and heteroaliphatic moieties may independently be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and each aryl, heteroaryl, alkylaryl, and alkylheteroaryl moiety may be substituted or unsubstituted;
• wherein one or any two of R1, RA, R2, RB, R3, RC, R4, RD, R5, R6, or RJ, are optionally a linker covalently bonded to a compound selected from the group consisting of radicicol, monocillin, geldanamycin, and steroids;
• and
• pharmaceutically acceptable derivatives thereof.

A compound having the structure:

• wherein R1 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or N(RA)2, wherein each occurrence of RA is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R2 is hydrogen, halogen, cyano, —ORB, —N(RB)2, —SRB, —O(C═O)RB, —N(RB)(C═O)(RB), —C(O)RB, —C(O)ORB, —CON(RB)2, —OCO2RB, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RB is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R3 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or —N(RC)2, wherein each occurrence of RC is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R4 is hydrogen, halogen, cyano, —ORD, —N(RD)2, —SRD, —O(C═O)RD, —N(RD)(C═O)(RD), —C(O)RD, —C(O)ORD, —CON(RD)2, —OCO2RD, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RD is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• Z is O;
• X is O;
• A and B together represent
• —CHR5—CHR6—, —CR5═CR6—, wherein R5 and R6 are each independently hydrogen, halogen, cyano, —ORJ, —N(RJ)2, —SRJ, —O(C═O)RJ, —O(S═O)RJ, —N(RJ)(C═O)(RJ), —C(═O)RJ, —C(═O)ORJ, —CON(RJ)2, —OCO2RJ, —OSO2RJ, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, and wherein R7 is hydrogen, —ORK, —SRK, —C(O)ORK, —S(O)2RK, —O(C═O)RK, —N(RK)(C═O)(RK), —C(O)RK, —C(O)ORK, —CON(RK)2, —OCO2RK, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RK is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or when A and B together represent —CHR5—CHR6—, R5 and R6 taken together represent a substituted or unsubstituted 3–7 membered aliphatic, heteroaliphatic, aryl or heteroaryl ring,
• D and E together represent —CHR8—CHR9—, —CR8═CR9—, wherein R8 and R9 are each independently hydrogen or lower alkyl;
• G and J together represent —CHR10—CHR11, —CR10═CR11—, wherein R10 and R11 are each independently hydrogen or lower alkyl;
• whereby each of the foregoing aliphatic and heteroaliphatic moieties may independently be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and each aryl, heteroaryl, alkylaryl, and alkylheteroaryl moiety may be substituted or unsubstituted;
• wherein one or any two of R1, RA, R2, RB, R3, RC, R4, RD, R5, R6, or RJ, are optionally a linker covalently bonded to a compound selected from the group consisting of radicicol, monocillin, geldanamycin, and steroids;
• and
• pharmaceutically acceptable derivatives thereof.

A method for treating a cancer selected from the group consisting of breast cancers, lung cancers, glioblastoma (brain), and retinoblastoma (eye) comprising:

• administering a therapeutically effective amount of a compound having the structure:
• wherein the dotted line - - - represents an optional bond, such that either a single or a double bond is present;
• R1 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or N(RA)2, wherein each occurrence of RA is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R2 is hydrogen, halogen, cyano, —ORB, —N(RB)2, —SRB, —O(C═O)RB, —N(RB)(C═O)(RB), —C(O)RB, —C(O)ORB, —CON(RB)2, —OCO2RB, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RB is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R3 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or —N(RC)2, wherein each occurrence of RC is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R4 is hydrogen, halogen, cyano, —ORD, —N(RD)2, —SRD, —O(C═O)RD, —N(RD)(C═O)(RD), —C(O)RD, —C(O)ORD, —CON(RD)2, —OCO2RD, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RD is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• Z is O;
• X is O;
• K and L together represent C═O, C═S, CH—CH3, CH—CH(RL)2, C═C(RL)2, —CH2—, —C(—S(CH2)3S—)—, CH—ORL, CH—SRL, CH—N(RL)2, CH—N(RL)(C═O)(RL), C═N—O—RL, CH—N═O, C═C(RL)—N(RL)2, C═N—RL, C═N—N(RL)2, or, if the dotted line - - - represents a bond, whereby a double bond is present, then K and L together represent C—N(RL)2, wherein each occurrence of RL is independently hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or two occurrences of RL taken together represent a 3 to 7-membered cyclic aliphatic, heteroaliphatic, aromatic or heteroaromatic moiety;
• whereby each of the foregoing aliphatic and heteroaliphatic moieties may independently be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and each aryl, heteroaryl, alkylaryl, and alkylheteroaryl moiety may be substituted or unsubstituted;
• wherein one or any two of R1, RA, R2, RB, R3, RC, R4, RD, or RL are optionally a linker covalently bonded to a compound selected from the group consisting of radicicol, monocillin, geldanamycin, and steroids;
• and
• pharmaceutically acceptable derivatives thereof,
• to a subject in need thereof.

A method for inhibiting the growth of or killing cancer cells, said method comprising:

• contacting cancer cells with an amount of a compound having the structure:
• wherein the dotted line - - - represents an optional bond, such that either a single or a double bond is present;
• R1 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or N(RA)2, wherein each occurrence of RA is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R2 is hydrogen, halogen, cyano, —ORB, —N(RB)2, —SRB, —O(C═O)RB, —N(RB)(C═O)(RB), —C(O)RB, —C(O)ORB, —CON(RB)2, —OCO2RB, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RB is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R3 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or —N(RC)2, wherein each occurrence of RC is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R4 is hydrogen, halogen, cyano, —ORD, —N(RD)2, —SRD, —O(C═O)RD, —N(RD)(C═O)(RD), —C(O)RD, —C(O)ORD, —CON(RD)2, —OCO2RD, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RD is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• Z is O;
• X is O;
• K and L together represent C═O, C═S, CH—CH3, CH—CH(RL)2, C═C(RL)2, —CH2—, —C(—S(CH2)3S—)—, CH—ORL, CH—SRL, CH—N(RL)2, CH—N(RL)(C═O)(RL), C═N—O—RL, CH—N═O, C═C(RL)—N(RL)2, C═N—RL, C═N—N(RL)2, or, if the dotted line - - - represents a bond, whereby a double bond is present, then K and L together represent C—N(RL)2, wherein each occurrence of RL is independently hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or two occurrences of RL taken together represent a 3 to 7-membered cyclic aliphatic, heteroaliphatic, aromatic or heteroaromatic moiety;
• whereby each of the foregoing aliphatic and heteroaliphatic moieties may independently be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and each aryl, heteroaryl, alkylaryl, and alkylheteroaryl moiety may be substituted or unsubstituted;
• wherein one or any two of R1, RA, R2, RB, R3, RC, R4, RD, or RL are optionally a linker covalently bonded to a compound selected from the group consisting of radicicol, monocillin, geldanamycin, and steroids;
• and
• pharmaceutically acceptable derivatives thereof;
• effective to inhibit the growth of or kill the cancer cells, wherein the cancer cells are selected from the group consisting of breast cancer cells, lung cancer cells, glioblastoma (brain) cells, and retinoblastoma (eye) cells.

A compound having the structure:

• wherein the dotted line - - - represents an optional bond, such that either a single or a double bond is present;
• R1 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or N(RA)2, wherein each occurrence of RA is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R2 is hydrogen, halogen, cyano, —ORB, —N(RB)2, —SRB, —O(C═O)RB, —N(RB)(C═O)(RB), —C(O)RB, —C(O)ORB, —CON(RB)2, —OCO2RB, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RB is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R3 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or —N(RC)2, wherein each occurrence of RC is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R4 is hydrogen, halogen, cyano, —ORD, —N(RD)2, —SRD, —O(C═O)RD, —N(RD)(C═O)(RD), —C(O)RD, —C(O)ORD, —CON(RD)2, —OCO2RD or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RD is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• Z is O;
• X is O;
• K and L together represent C═O, C═S, CH—CH3, CH—CH(RL)2, C═C(RL)2, —CH2—, —C(—S(CH2)3S—)—, CH—ORL, CH—SRL, CH—N(RL)2, CH—N(RL)(C═O)(RL), C═N—O—RL, CH—N═O, C═C(RL)—N(RL)2, C═N—RL, C═N—N(RL)2, or, if the dotted line - - - represents a bond, whereby a double bond is present, then K and L together represent C—N(RL)2, wherein each occurrence of RL is independently hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or two occurrences of RL taken together represent a 3 to 7-membered cyclic aliphatic, heteroaliphatic, aromatic or heteroaromatic moiety;
• whereby each of the foregoing aliphatic and heteroaliphatic moieties may independently be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and each aryl, heteroaryl, alkylaryl, and alkylheteroaryl moiety may be substituted or unsubstituted;
• wherein one or any two of R1, RA, R2, RB, R3, RC, R4, RD, or RL are optionally a linker covalently bonded to a compound selected from the group consisting of radicicol, monocillin, geldanamycin, and steroids;
• and
• pharmaceutically acceptable derivatives thereof.

A pharmaceutical composition for treating a cancer selected from the group consisting of breast cancers, lung cancers, glioblastoma (brain), and retinoblastoma (eye) comprising a compound having the structure:

• wherein the dotted line - - - represents an optional bond, such that either a single or a double bond is present;
• R1 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or N(RA)2, wherein each occurrence of RA is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R2 is hydrogen, halogen, cyano, —ORB, —N(RB)2, —SRB, —O(C═O)RB, —N(RB)(C═O)(RB), —C(O)RB, —C(O)ORB, —CON(RB)2, —OCO2RB, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RB is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R3 is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or —N(RC)2, wherein each occurrence of RC is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• R4 is hydrogen, halogen, cyano, —ORD, —N(RD)2, —SRD, —O(C═O)RD, —N(RD)(C═O)(RD), —C(O)RD, —C(O)ORD, —CON(RD)2, —OCO2RD, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, wherein each occurrence of RD is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
• Z is O;
• X is O;
• K and L together represent C═O, C═S, CH—CH3, CH—CH(RL)2, C═C(RL)2, —CH2—, —C(—S(CH2)3S—)—, CH—ORL, CH—SRL, CH—N(RL)2, CH—N(RL)(C═O)(RL), C═N—O—RL, CH—N═O, C═C(RL)—N(RL)2, C═N—RL, C═N—N(RL)2, or, if the dotted line - - - represents a bond, whereby a double bond is present, then K and L together represent C—N(RL)2, wherein each occurrence of RL is independently hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or two occurrences of RL taken together represent a 3 to 7-membered cyclic aliphatic, heteroaliphatic, aromatic or heteroaromatic moiety;
• whereby each of the foregoing aliphatic and heteroaliphatic moieties may independently be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and each aryl, heteroaryl, alkylaryl, and alkylheteroaryl moiety may be substituted or unsubstituted;
• wherein one or any two of R1, RA, R2, RB, R3, RC, R4, RD, or RL are optionally a linker covalently bonded to a compound selected from the group consisting of radicicol, monocillin, geldanamycin, and steroids;
• and
• pharmaceutically acceptable derivatives thereof,
• and a pharmaceutically acceptable carrier.