Compounds for treating proliferative disorders

A compound represented by formula (XX):

• or a tautomer, pharmaceutically acceptable salt, or prodrug thereof, wherein:
• Z7 are Z8 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Y2 is a covalent bond, an optionally substituted C1-C6 alkylene group, —N(R5)— or —C(═X5)—;
• Y3 is —C(O)— or —S(O)q—;
• X5 is C(R9)2 or N—X6;
• X6 is R17, —OR17, —N(R26)2, or —NHR27;
• R″1 and R″2 are independently 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 an optionally substituted heteroaryl;
• R3 and R4 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 an optionally substituted heteroaryl;
• R5 and R6 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 an optionally substituted heteroaryl;
• each R9 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, halo, nitro, cyano, guanadino, —OR17, —NR40R41, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pNR19R20;
• R13 for each occurrence is, independently, —H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pNR19R20, 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;
• R17 and R18, 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;
• R19 and R20, 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 R19 and R20, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• R26 is 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;
• R27 is —H, 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;
• R40 and R41, for each occurrence, are independently H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, 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 R40 and R41, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• m is 0 or 1;
• p is 1 or 2;
• and
• q is 1 or 2.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following formulas:

• or a tautomer, pharmaceutically acceptable salt, or prodrug thereof wherein:
• Z1 are Z2 are independently O, S, Se, Te, Po, NR13, SbR13 or BiR13;
• Z′1 and Z′2 are independently Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z3 and Z4 are independently O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• provided that when one of Z1 or Z2 is S and the other is O or S, then Z3 and Z4 are not O or S, and provided that when Z1 and Z2 are both O, then Z3 and Z4 are not both S;
• Z′3 and Z′4 are independently N, P, As, Sb, or Bi;
• Z5 are Z6 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z7 are Z8 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Y is a covalent bond, an optionally substituted C1-C6 alkylene group, —C(═X5)—, or —N(R5)—;
• or Y is —C(R5)p— and taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group,
• Y′ taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group,
• Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group,
• Y2 is a covalent bond, an optionally substituted C1-C6 alkylene group, —N(R5)— or
• Y3 is —C(O)— or —S(O), —
• X1 and X2 are each independently C(R3)p, O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m or Bi(R13)m;
• X3 is C(R1)p, O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• X5 is C(R9)2 or N—X6;
• X6 is R17, OR17, —N(R26)2, or —NHR27;
• R″1 and R″2 are independently 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 an optionally substituted heteroaryl:
• R3 and R4 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 an optionally substituted heteroaryl:
• R5 and R6 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 an optionally substituted heteroaryl:
• R7 and R8 are each independently —H or an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, or R7 is —H and R8 is an optionally substituted aryl or an optionally substituted heteroaryl.
• each R9 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, halo, nitro, cyano, guanadino, —OR17, —NR40R41, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pNR19R20;
• R13 for each occurrence is, independently, —H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pR19R20, 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;
• R17 and R18, 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:
• R19 and R20, 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 R19 and R20, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• R22 is 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;
• R26 is 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;
• R27 is —H, 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;
• R40 and R41 for each occurrence, are independently H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, 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 R40 and R41, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• m is 0 or 1;
• p is 1 or 2;
• q is 1 or 2;
• and
• with the provisos that
• when Z1 and Z2 are both O or both S and Z3 and Z4 are both N(R13)m, then Y taken together with both >C=Z3 and >C=Z4 does not form not an optionally substituted pyrimidine ring or an optionally substituted pyrazole ring;
• when Z1, Z2, Z3, and Z4 are all O and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 can not all be —H;
• when Z1. Z2, Z3, and Z4 are all O and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl;
• when Z3 and Z4 are both O, Z1 and Z2 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 can not all be —H;
• when Z1 and Z2 are both O and Z3 and Z4 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• when Z5, and Z6 are both O or NH, and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• and
• when Z5, and Z6 are both O and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl.

A method of treating a subject having a proliferative disorder, said method comprising administering to the subject an effective amount of a compound represented by the following formulas:

• or a tautomer, pharmaceutically acceptable salt, or prodrug thereof, wherein:
• Z1 are Z2 are independently O, S, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z′1 and Z′2 are independently Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z3 and Z4 are independently O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• provided that when one of Z1 or Z2 is S and the other is O or S, then Z3 and Z4 are not O or S, and provided that when Z1 and Z2 are both O, then Z3 and Z4 are not both S;
• Z′3 and Z′4 are independently N, P, As, Sb, or Bi;
• Z5 are Z6 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z7 are Z8 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Y is a covalent bond, an optionally substituted C1-C6 alkylene group, —C(═X5)—, or —N(R5)—;
• or Y is —C(R5)p— and taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group;
• Y′ taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group:
• Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group;
• Y2 is a covalent bond, an optionally substituted C1-C6 alkylene group, —N(R5)— or —C(═X5)—;
• Y3 is —C(O)— or —S(O)q—;
• X1 and X2 are each independently C(R3)p, O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m or Bi(R13)m;
• X3 is C(R)p, O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• X5 is C(R9)2 or N—X6;
• R″1 and R″2 are independently 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 an optionally substituted heteroaryl;
• R3 and R4 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 an optionally substituted heteroaryl;
• R5 and R6 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 an optionally substituted heteroaryl;
• R7 and R8 are each independently —H or an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, or R7 is —H and R8 is an optionally substituted aryl or an optionally substituted heteroaryl.
• each R9 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, halo, nitro, cyano, guanadino, —OR17, —NR40R41, —C(O)R17, —C(R)OR17, —OC(O)R17, —C(O)NR19R20, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pNR19R20;
• R13 for each occurrence is, independently, —H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, —OP(O)(OR17)2, —SP(O)(OR17)2m —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pNR19R20 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;
• R17 and R18, 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;
• R19 and R20, 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 R19 and R20, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• R22 is 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;
• R26 is 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;
• R27 is —H, 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;
• R40 and R41, for each occurrence, are independently H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, 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 R40 and R41, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• m is 0 or 1;
• p is 1 or 2;
• q is 1 or 2;
• and
• with the provisos that
• when Z1 and Z2 are both O or both S and Z3 and Z4 are both N(R13)m, then Y taken together with both >C=Z3 and >C=Z4 does not form not an optionally substituted pyrimidine ring or an optionally substituted pyrazole ring;
• when Z1, Z2, Z3, and Z4 are all O and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 can not all be —H;
• when Z1, Z2, Z3, and Z4 are all O, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl;
• when Z3 and Z4 are both O, Z1 and Z2 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 can not all be —H;
• when Z1 and Z2 are both O and Z3 and Z4 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• when Z5, and Z6 are both O or NH, and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• and
• when Z5, and Z6 are both O and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl.

A method of treating a subject with a cancer or preventing the reoccurrence of cancer in a subject, said method comprising administering to the subject an effective amount of a compound represented by the following formulas:

• or a tautomer, pharmaceutically acceptable salt, or prodrug thereof, wherein:
• Z1 are Z2 are independently O, S. Se, Te, Po, NR13, PR13, AsR13. SbR13 or BiR13;
• Z′1 and Z′2 are independently Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z3 and Z4 are independently O, S. Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• provided that when one of Z1 or Z2 is S and the other is O or S, then Z3 and Z4 are not O or S, and provided that when Z1 and Z2 are both O, then Z3 and Z4 are not both S;
• Z′3 and Z′4 are independently N. P, As, Sb, or Bi;
• Z5 are Z6 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z7 are Z8 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Y is a covalent bond, an optionally substituted C1-C6 alkylene group, —C(═X5)—, or —N(R5)—;
• or Y is —C(R5)p— and taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group;
• Y′ taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group;
• Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group;
• Y2 is a covalent bond, an optionally substituted C1-C6 alkylene group, —N(R5)— or —C(═X5)—;
• Y3 is —C(O)— or —S(O)g—;
• X1 and X2 are each independently C(R3)p. O, S. Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m or Bi(R13)m;
• X3 is C(R3)p, O, S. Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• X5 is C(R9)2 or N—X6;
• X6 is R17, —O17, —N(R26)2, or —NHR27;
• R″1 and R″2 are independently 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 an optionally substituted heteroaryl;
• R3 and R4 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 an optionally substituted heteroaryl;
• R5 and R6 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 an optionally substituted heteroaryl;
• R7 and R8 are each independently —H or an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, or R7 is —H and R8 is an optionally substituted aryl or an optionally substituted heteroaryl;
• each R9 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, halo, nitro, cyano, guanadino, —OR17, —NR40R41, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pNR19R20;
• R13 for each occurrence is, independently, —H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pR19R20, 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;
• R17 and R18, 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;
• R19 and R20, 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 R19 and R20, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• R22 is 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;
• R26 is 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;
• R27 is —H, 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
• R40 and R41, for each occurrence, are independently H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, 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 R40 and R41, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• m is 0 or 1;
• p is 1 or 2;
• q is 1 or 2;
• and
• with the provisos that
• when Z1 and Z2 are both O or both S and Z3 and Z4 are both N(R13)m, then Y taken together with both >C=Z3 and >C=Z4 does not form not an optionally substituted pyrimidine ring or an optionally substituted pyrazole ring;
• when Z1, Z2, Z3, and Z4 are all O and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 can not all be —H;
• when Z1, Z2, Z3, and Z4 are all O, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl;
• when Z3 and Z4 are both O, Z1 and Z2 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 can not all be —H;
• when Z1 and Z2 are both O and Z3 and Z4 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• when Z5, and Z6 are both O or NH, and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• and
• when Z5 and Z6 are both O and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl.

A method of treating or inhibiting angiogenesis in a subject in need thereof, comprising administering to the subject an effective amount of a compound represented by the following formulas:

• or a tautomer, pharmaceutically acceptable salt, or prodrug thereof, wherein:
• Z1 are Z2 are independently O, S. Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z′1 and Z′2 are independently Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z3 and Z4 are independently O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• provided that when one of Z1 or Z2 is S and the other is O or S, then Z3 and Z4 are not O or S, and provided that when Z1 and Z2 are both O, then Z3 and Z4 are not both S;
• Z′3 and Z′4 are independently N. P, As, Sb, or Bi;
• Z5 are Z6 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z7 are Z8 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Y is a covalent bond, an optionally substituted C1-C6 alkylene group, —C(═X5)—, or —N(R5)—;
• or Y is —C(R5)p— and taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group.
• Y′ taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group;
• Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group;
• Y2 is a covalent bond, an optionally substituted C1-C6 alkylene group —N(R5)— or —C(═X5)—;
• Y3 is —C(O)— or —S(O)q—;
• X1 and X2 are each independently C(R3)p. O, S. Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m or Bi(R13)m;
• X3 is C(R3)p, O, S. Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• X5 is C(R9)2 or N—X6;
• X6 is R17, —OR17, —N(R26)2, or —NHR27;
• R″1 and R″2 are independently 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 an optionally substituted heteroaryl;
• R3 and R4 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 an optionally substituted heteroaryl;
• R5 and R6 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 an optionally substituted heteroaryl;
• R7 and R8 are each independently —H or an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, or R7 is —H and R8 is an optionally substituted aryl or an optionally substituted heteroaryl;
• each R9 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, halo, nitro, cyano, guanadino, —OR17, —NR40R41, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pNR19R20;
• R13 for each occurrence is, independently, —H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pNR19R20, 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;
• R17 and R18, 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;
• R19 and R20, 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 R19 and R20, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• R22 is 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;
• R26 is 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;
• R27 is —H, 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;
• R40 and R41, for each occurrence, are independently H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, 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 R40 and R41, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• m is 0 or 1;
• p is 1 or 2:
• q is 1 or 2;
• and
• with the provisos that
• when Z1 and Z2 are both O or both S and Z3 and Z4 are both N(R13)m, then Y taken together with both >C=Z3 and >C=Z4 does not form not an optionally substituted pyrimidine ring or an optionally substituted pyrazole ring;
• when Z1, Z2, Z3, and Z4 are all O and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 can not all be —H;
• when Z1, Z2, Z3, and Z4 are all O, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl;
• when Z3 and Z4 are both O, Z1 and Z2 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 can not all be —H;
• when Z1, and Z2 are both O and Z3 and Z4 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• when Z5 and Z6 are both O or NH, and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• and
• when Z5, and Z6 are both O and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl.

A method of treating or preventing an Hsp70 responsive disorder, comprising administering to a subject an effective amount of a compound represented by the following formulas:

• or a tautomer, pharmaceutically acceptable salt, or prodrug thereof, wherein:
• Z1 are Z_are independently O, S, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z′1 and Z′2 are independently Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z3 and Z4 are independently O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• provided that when one of Z1 or Z2 is S and the other is O or S, then Z3 and Z4 are not O or S, and provided that when Z1 and Z2 are both O, then Z3 and Z4 are not both S;
• Z′3 and Z′4 are independently N, P, As, Sb, or Bi;
• Z5 are Z6 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z7 are Z8 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Y is a covalent bond, an optionally substituted C1-C6 alkylene group, —C(═X5)—, or —N(R5)—;
• or Y is —C(R51)— and taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group;
• Y′ taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group;
• Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group;
• Y2 is a covalent bond, an optionally substituted C1-C6 alkylene group, —N(R5)— or
• Y3 is —C(O)— or —S(O)q—;
• X1 and X2 are each independently C(R3)p, O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m or Bi(R13)m;
• X3 is C(R3)p, O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• X5 is C(R9)2 or N—X6;
• X6 is R17, —OR17, —N(R26)2, or —NHR27;
• R″1 and R″2 are independently 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 an optionally substituted heteroaryl;
• R3 and R4 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 an optionally substituted heteroaryl;
• R5 and R6 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 an optionally substituted heteroaryl;
• R7 and R8 are each independently —H or an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, or R7 is —H and R8 is an optionally substituted aryl or an optionally substituted heteroaryl;
• each R9 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, halo, nitro, cyano, guanadino, —OR17, —NR40R41, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)R17, or —S(O)pNR19R20;
• R13 for each occurrence is, independently, —H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pNR19R20, 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;
• R17 and R18, 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;
• R19 and R20, 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 R19 and R20, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• R22 is 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.
• R26 is 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;
• R27 is —H, 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;
• R40 and R41, for each occurrence, are independently H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, 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 R40 and R41, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• m is 0 or 1;
• p is 1 or 2;
• q is 1 or 2;
• and
• with the provisos that
• when Z1 and Z2 are both O or both S and Z3 and Z4 are both N(R13)m, then Y taken together with both >C=Z3 and >C=Z4 does not form not an optionally substituted pyrimidine ring or an optionally substituted pyrazole ring;
• when Z1, Z2, Z3, and Z4 are all O and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 can not all be —H;
• when Z1, Z2, Z3, and Z4 are all O, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl;
• when Z3 and Z4 are both O, Z1 and Z2 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 can not all be —H;
• when Z1 and Z2 are both O and Z3 and Z4 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• when Z5, and Z6 are both O or NH, and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• and
• when Z5, and Z6 are both O and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl.

A method of treating a natural killer cell responsive disorder, comprising administering to a subject an effective amount of a compound represented by the following formulas:

• or a tautomer, pharmaceutically acceptable salt, or prodrug thereof, wherein:
• Z1 are Z2 are independently O, S, Se, Te, Po, NR13, PR13, AsR—3 SbR13 or BiR13;
• Z′1 and Z′2 are independently Se, Te, Po, NR3, PR13, AsR3, SbR3 or BiR13;
• Z3 and Z4 are independently O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• provided that when one of Z1 or Z2 is S and the other is O or S, then Z3 and Z4 are not O or S, and provided that when Z1 and Z2 are both O, then Z3 and Z4 are not both S;
• Z′1 and Z′4 are independently N, P, As, Sb, or Bi;
• Z5 are Z6 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Z7 are Z8 are independently O, Se, Te, Po, NR13, PR13, AsR13, SbR13 or BiR13;
• Y is a covalent bond, an optionally substituted C1-C6 alkylene group, —C(═X5)—, or —N(R5)—;
• or Y is —C(R5)p— and taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group;
• Y′ taken together with both >C=Z3 and >C=Z4 groups to which it is bonded, forms an optionally substituted monocyclic aromatic group;
• Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group.
• Y2 is a covalent bond, an optionally substituted C1-C6 alkylene group, —N(R5)— or —C(═X5)—;
• Y3 is —C(O)— or —S(O)q—;
• X1 and X2 are each independently C(R3)p, O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m or Bi(R13)m;
• X3 is C(R3)p, O, S, Se, Te, Po, N(R13)m, P(R13)m, As(R13)m, Sb(R13)m, or Bi(R13)m;
• X5 is C(R9)2 or N—X6;
• X6 is R17, —OR17, —N(R26)2, or —NHR27;
• R″1 and R″2 are independently 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 an optionally substituted heteroaryl;
• R3 and R4 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 an optionally substituted heteroaryl;
• R5 and R6 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 an optionally substituted heteroaryl;
• R7 and R8 are each independently —H or an optionally substituted alkyl an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, or R7 is —H and R8 is an optionally substituted aryl or an optionally substituted heteroaryl;
• each R9 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, halo, nitro, cyano, guanadino, —OR17, —NR40R41, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)R17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pNR19R20;
• R13 for each occurrence is, independently, —H, —OR17, —NR19R20, —C(O)R17, —C(O)OR17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, —OP(O)(OR17)2, —SP(O)(OR17)2, —SR17, —S(O)pR17, —OS(O)pR17, —S(O)pOR17, —NR18S(O)pR17, or —S(O)pNR19R20, 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;
• R17 and R18, 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;
• R19 and R20, 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 R19 and R20, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• R22 is 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;
• R26 is 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;
• R27 is —H, 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;
• R40 and R41, for each occurrence, are independently H, —OR7, —NR19R20, —C(O)R17, —C(O)R17, —OC(O)R17, —C(O)NR19R20, —NR18C(O)R17, 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 R40 and R41, taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;
• m is O or 1;
• p is 1 or 2;
• q is 1 or 2;
• and
• with the provisos that
• when Z1 and Z2 are both O or both S and Z3 and Z4 are both N(R13)m, then Y taken together with both >C=Z3 and >C=Z4 does not form not an optionally substituted pyrimidine ring or an optionally substituted pyrazole ring;
• when Z1, Z2, Z3, and Z4 are all O and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 can not all be —H;
• when Z1, Z2, Z3, and Z4 are all O, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl;
• when Z3 and Z4 are both O, Z1 and Z2 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R can not all be —H;
• when Z1 and Z2 are both O and Z3 and Z4 are both NH, and Y is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• when Z5, and Z6 are both O or NH, and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R3, R4, R5, and R6 are not all —H;
• and
• when Z5, and Z6 are both O and Y″ is a covalent bond, or a substituted or unsubstituted C1-C6 alkylene group, then R″1 and R″2 are not both methyl.