Treatment of Breast Cancer

A method of treating triple negative breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (II):

• wherein:
• Het represents a heterocyclic unit of 5 or 6 atoms;
• A and B are independently selected from oxygen, sulfur, and N—R9;
• R1 is selected from hydrogen, aryl, substituted aryl, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, halogenated alkyl, halogenated alkenyl, halogenated alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic, cycloalkyl, substituted cycloalkyl, SO2R11, NR11R12, NR12(CO)OR11, NH(CO)NR11R12, NR12(CO)R11, O(CO)R11, O(CO)OR11, O(CS)R11, NR12(CS)R11, NH(CS)NR11R12, or NR12(CS)OR11;
• R2 and R3 are independently selected from hydrogen, aryl, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, halogenated alkyl, halogenated alkenyl, halogenated alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic, cycloalkyl, or substituted cycloalkyl, or, together with the carbon to which they are linked, form a cycle which can be cycloalkyl, substituted cycloalkyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic;
• or R2 and R3 can be connected to form a cycle which can be heterocyclic aromatic or non aromatic, substituted heterocyclic aromatic or non aromatic;
• R9 is selected from hydrogen, aryl, substituted aryl, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, halogenated alkyl, halogenated alkenyl, halogenated alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic, cycloalkyl, substituted cycloalkyl, SO2R11, NR11R12, NR12(CO)OR11, NH(CO)NR11R12, NR12(CO)R11, O(CO)R11, O(CO)OR11, O(CS)R11, NR12(CS)R11, NH(CS)NR11R12, or NR12(CS)OR11;
• and
• R11 and R12 are independently selected from hydrogen, alkyl, substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, aryl, substituted aryl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, or substituted heterocyclic aromatic or non-aromatic;
• or R11 and R12 can be connected to form a cycle which can be heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic, cycloalkyl, or substituted cycloalkyl.

A method of treating triple negative breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (III)

• wherein:
• W1 is CN, NO2 or SO2R4;
• W2 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or halogen;
• Z1 is S or O
• Z2 is S, O or NR4;
• Y1 and Y2 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, arylalkenyl, arylalkynyl, heteroaralkyl, heterocyclyl, substituted heterocyclyl or Y1 and Y2 are connected to form a cycle which can be heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl;
• T is carbon or nitrogen and can be at any position in the ring;
• R1 is —C1-C8alkyl-NRaRb, —O—C1-C8alkyl-NRcRd or —C(O)NReRf, where:
• Ra is a C2-C12alkyl and Rb is H or a C1-C2alkyl or Ra and Rb are taken together with the N to which they are attached to form a heterocyclic ring;
• Rc is a C1-C12alkyl and Re is H or a C1-C12alkyl or Rc and Rd are taken together with the N to which they are attached to form a heterocyclic ring;
• Re is a C2-C12alkyl and Rf is H or a C1-C2alkyl, or
• Re is a C1-C12alkyl and Rf is C1-C2alkyl, or
• Re and Rf are taken together with the N to which they are attached to form a heterocyclic ring;
• R2 is hydrogen, halogen, nitro, alkyl and substituted alkyl;
• and
• R4 is independently H, alkyl, or aryl.

A method of treating triple negative breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (IV):

• wherein:
• W1 is CN, NO2 or SO2R4;
• W2 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or halogen;
• Z is S, O or NR5;
• Y1 and Y2 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, arylalkenyl, arylalkynyl, heteroaralkyl, heterocyclyl, substituted heterocyclyl or Y1 and Y2 are taken together with the carbon to which they are attached to form a cycle which can be heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl;
• T is carbon or nitrogen and can be at any position in the ring;
• R1 is —C1-C8 alkyl-NRaRb, —O—C1-C8 alkyl-NRcRd or —C(O)NReRf,
• Ra is a C1-C12 alkyl and Rb is H or a C1-C12 alkyl or Ra and Rb are taken together with the N to which they are attached to form a heterocyclic ring;
• Rc is a C1-C12 alkyl and Rd is H or a C1-C12 alkyl or Rc and Rd are taken together with the N to which they are attached to form a heterocyclic ring;
• Re is a C1-C12 alkyl and Rf is H or a C1-C12 alkyl, or Re and Rf are taken together with the N to which they are attached to form a heterocyclic ring;
• R2 is hydrogen, halogen, nitro, alkyl or substituted alkyl;
• R4 is H, alkyl, substituted alkyl, aryl or substituted aryl;
• and
• R5 is H, alkyl, substituted alkyl, aryl or substituted aryl.

A method of treating triple negative breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (V):

• wherein:
• W1 is CN, NO2 or SO2R4;
• W2 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or halogen;
• Z is S, O or NR5;
• Y1 and Y2 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, arylalkenyl, arylalkynyl, heteroaralkyl, heterocyclyl, substituted heterocyclyl or Y1 and Y2 are taken together with the carbon to which they are attached to form a cycle which can be heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl;
• Y3 is carboxyl, formyl, alkyl carbonyl, substituted alkyl carbonyl, alkenyl carbonyl, substituted alkenyl carbonyl, alkynyl carbonyl, substituted alkynyl carbonyl, aryl carbonyl, substituted aryl carbonyl, heteroaryl carbonyl, substituted heteroaryl carbonyl, arylalkyl carbonyl, arylalkenyl carbonyl, arylalkynyl carbonyl, heteroaralkyl carbonyl, heterocyclyl carbonyl, substituted heterocyclyl carbonyl, cyano, aminocarbonyl, N-alkyl aminocarbonyl, N,N-dialkyl aminocarbonyl, N-substituted alkyl aminocarbonyl, N,N-bis-substituted alkyl aminocarbonyl, alkoxy carbonyl, substituted alkoxy carbonyl, halocarbonyl, hydroxymethyl, alkylhydroxymethyl, substituted alkoxymethyl, thiocarboxyl, thioformyl, alkyl thiocarbonyl, substituted alkyl thiocarbonyl, alkenyl thiocarbonyl, substituted alkenyl thiocarbonyl, alkynyl thiocarbonyl, substituted alkynyl thiocarbonyl, aryl thiocarbonyl, substituted aryl thiocarbonyl, heteroaryl thiocarbonyl, substituted heteroaryl thiocarbonyl, arylalkyl thiocarbonyl, arylalkenyl thiocarbonyl, arylalkynyl thiocarbonyl, heteroaralkyl thiocarbonyl, heterocyclyl thiocarbonyl, substituted heterocyclyl thiocarbonyl, thiocarbamyl, N-alkyl thiocarbamyl, N,N-dialkyl thiocarbamyl, N-substituted alkyl thiocarbamyl, N,N-bis-substituted alkyl thiocarbamyl, alkoxy thiocarbonyl, substituted alkoxy thiocarbonyl, halothiocarbonyl, mercaptomethyl, substituted alkylthiomethyl;
• heteroaryl carbonyl, substituted heteroaryl carbonyl, arylalkyl carbonyl, arylalkenyl carbonyl, arylalkynyl carbonyl, heteroaralkyl carbonyl, heterocyclyl carbonyl, substituted heterocyclyl carbonyl, cyano, aminocarbonyl, N-alkyl aminocarbonyl, N,N-dialkyl aminocarbonyl, N-substituted alkyl aminocarbonyl, N,N-bis-substituted alkyl aminocarbonyl, alkoxy carbonyl, substituted alkoxy carbonyl, halocarbonyl, hydroxymethyl, alkoxymethyl, substituted alkoxymethyl;
• T is carbon or nitrogen and can be at any position in the ring;
• R1 is hydrogen, —C1-C8 alkyl-NRaRb, —O—C1-C8 alkyl-NRcRd, —C(O)NReRf or —NRgRh,
• Ra is a C1-C12 alkyl and Rb is H or a C1-C12 alkyl or Ra and Rb are taken together with the N to which they are attached to form a heterocyclic ring;
• Rc is a C1-C12 alkyl and Rd is H or a C1-C12 alkyl or Rc and Rd are taken together with the N to which they are attached to form a heterocyclic ring;
• Re is H or a C1-C12 alkyl and Rf is H or a C1-C12 alkyl, or Re and Rf are taken together with the N to which they are attached to form a heterocyclic ring;
• Rg is H or a C1-C12 alkyl and Rh is H or a C1-C12 alkyl, or Rg and Rh are taken together with the N to which they are attached to form a heterocyclic ring;
• R2 is hydrogen, halogen, nitro, alkyl or substituted alkyl;
• R4 is H, alkyl, substituted alkyl, aryl or substituted aryl;
• and
• R5 is H, alkyl, substituted alkyl, aryl or substituted aryl.

A method of treating triple negative breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (VI):

• and
• wherein:
• X is S or O, and
• when X is S, then R1 is OH or NH2;
• and
• when X is O then R1 is OH, NH2 or NHMe.

A method of treating breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein cells of the breast cancer express detectable estrogen receptor but the breast cancer is resistant to endocrine therapy, and wherein the compound is a compound of structural formula (I):

• wherein:
• X is selected from the group consisting of trifluoromethyl and iodo;
• W is selected from the group consisting of O and NR5, wherein R5 is selected from the group consisting of H, methyl, and
• wherein D is S or O and E is N or O and G is alkyl, aryl,
• substituted alkyl or substituted aryl;
• or D is S or O and E-G together are C1-C4 lower alkyl;
• R1 and R2 together comprise eight or fewer carbon atoms and are selected from the group consisting of alkyl, substituted alkyl including haloalkyl, and, together with the carbon to which they are linked, a cycloalkyl or substituted cycloalkyl group;
• R3 is selected from the group consisting of hydrogen, halogen, methyl, C1-C4 alkoxy, formyl, haloacetoxy, trifluoromethyl, cyano, nitro, hydroxyl, phenyl, amino, methylcarbamoyl, methoxycarbonyl, acetamido, methanesulfonamino, methanesulfonyl, 4-methanesulfonyl-1-piperazinyl, piperazinyl, and C1-C6 alkyl or alkenyl optionally substituted with hydroxyl, methoxycarbonyl, cyano, amino, amido, nitro, carbamoyl, or substituted carbamoyl including methylcarbamoyl, dimethylcarbamoyl, and hydroxyethylcarbamoyl, with the proviso that R3 is not methylaminomethyl or dimethylaminomethyl;
• and
• R4 is selected from the group consisting of hydrogen, halogen, alkyl, and haloalkyl.

A method of treating breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein cells of the breast cancer express detectable estrogen receptor but the breast cancer is resistant to endocrine therapy, and wherein the compound is a compound of structural formula (II):

• wherein:
• Het represents a heterocyclic unit of 5 or 6 atoms;
• A and B are independently selected from oxygen, sulfur, and N—R9;
• R1 is selected from hydrogen, aryl, substituted aryl, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, halogenated alkyl, halogenated alkenyl, halogenated alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic, cycloalkyl, substituted cycloalkyl, SO2R11, NR11R12, NR12(CO)OR11, NH(CO)NR11R12, NR12(CO)R11, O(CO)R11, O(CO)OR11, O(CS)R11, NR12(CS)R11, NH(CS)NR11R12, or NR12(CS)OR11;
• R2 and R3 are independently selected from hydrogen, aryl, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, halogenated alkyl, halogenated alkenyl, halogenated alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic, cycloalkyl, or substituted cycloalkyl, or, together with the carbon to which they are linked, form a cycle which can be cycloalkyl, substituted cycloalkyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic;
• or R2 and R3 can be connected to form a cycle which can be heterocyclic aromatic or non aromatic, substituted heterocyclic aromatic or non aromatic;
• R9 is selected from hydrogen, aryl, substituted aryl, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, halogenated alkyl, halogenated alkenyl, halogenated alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic, cycloalkyl, substituted cycloalkyl, SO2R11, NR11R12, NR12(CO)OR11, NH(CO)NR11R12, NR12(CO)R11, O(CO)R11, O(CO)OR11, O(CS)R11, NR12(CS)R11, NH(CS)NR11R12, or NR12(CS)OR11;
• and
• R11 and R12 are independently selected from hydrogen, alkyl, substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, aryl, substituted aryl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, or substituted heterocyclic aromatic or non-aromatic;
• or R11 and R12 can be connected to form a cycle which can be heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic, cycloalkyl, or substituted cycloalkyl.

A method of treating breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein cells of the breast cancer express detectable estrogen receptor but the breast cancer is resistant to endocrine therapy, and wherein the compound is a compound of structural formula (II):

• wherein:
• W1 is CN, NO2 or SO2R4;
• W2 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or halogen;
• Z1 is S or O
• Z2 is S, O or NR4;
• Y1 and Y2 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, arylalkenyl, arylalkynyl, heteroaralkyl, heterocyclyl, substituted heterocyclyl or Y1 and Y2 are connected to form a cycle which can be heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl;
• T is carbon or nitrogen and can be at any position in the ring;
• R is —C1-C8alkyl-NRaRb, —O—C1-C8alkyl-NRcRd or —C(O)NReRf, where:
• Ra is a C2-C12alkyl and Rb is H or a C1-C2alkyl or Ra and Rb are taken together with the N to which they are attached to form a heterocyclic ring;
• Rc is a C1-C12alkyl and Re is H or a C1-C12alkyl or Rc and Rd are taken together with the N to which they are attached to form a heterocyclic ring;
• Re is a C2-C12alkyl and Rf is H or a C1-C12alkyl, or
• Re is a C1-C12alkyl and Rf is C1-C12alkyl, or
• Re and Rf are taken together with the N to which they are attached to form a heterocyclic ring;
• R2 is hydrogen, halogen, nitro, alkyl and substituted alkyl;
• and
• R4 is independently H, alkyl, or aryl.

A method of treating breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein cells of the breast cancer express detectable estrogen receptor but the breast cancer is resistant to endocrine therapy, and wherein the compound is a compound of structural formula (IV):

• wherein:
• W1 is CN, NO2 or SO2R4;
• W2 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or halogen;
• Z is S, O or NR5;
• Y1 and Y2 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, arylalkenyl, arylalkynyl, heteroaralkyl, heterocyclyl, substituted heterocyclyl or Y1 and Y2 are taken together with the carbon to which they are attached to form a cycle which can be heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl;
• T is carbon or nitrogen and can be at any position in the ring;
• R1 is —C1-C8 alkyl-NRaRb, —O—C1-C8 alkyl-NRcRd or —C(O)NReRf,
• Ra is a C1-C12 alkyl and Rb is H or a C1-C12 alkyl or Ra and Rb are taken together with the N to which they are attached to form a heterocyclic ring;
• Rc is a C1-C12 alkyl and Rd is H or a C1-C12 alkyl or Rc and Rd are taken together with the N to which they are attached to form a heterocyclic ring;
• Re is a C1-C12 alkyl and Rf is H or a C1-C12 alkyl, or Re and Rf are taken together with the N to which they are attached to form a heterocyclic ring;
• R2 is hydrogen, halogen, nitro, alkyl or substituted alkyl;
• R4 is H, alkyl, substituted alkyl, aryl or substituted aryl;
• and
• R5 is H, alkyl, substituted alkyl, aryl or substituted aryl.

A method of treating breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein cells of the breast cancer express detectable estrogen receptor but the breast cancer is resistant to endocrine therapy, and wherein the compound is a compound of structural formula (V):

• wherein:
• W1 is CN, NO2 or SO2R4;
• W2 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or halogen;
• Z is S, O or NR5;
• Y1 and Y2 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, arylalkenyl, arylalkynyl, heteroaralkyl, heterocyclyl, substituted heterocyclyl or Y1 and Y2 are taken together with the carbon to which they are attached to form a cycle which can be heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl;
• Y3 is carboxyl, formyl, alkyl carbonyl, substituted alkyl carbonyl, alkenyl carbonyl, substituted alkenyl carbonyl, alkynyl carbonyl, substituted alkynyl carbonyl, aryl carbonyl, substituted aryl carbonyl, heteroaryl carbonyl, substituted heteroaryl carbonyl, arylalkyl carbonyl, arylalkenyl carbonyl, arylalkynyl carbonyl, heteroaralkyl carbonyl, heterocyclyl carbonyl, substituted heterocyclyl carbonyl, cyano, aminocarbonyl, N-alkyl aminocarbonyl, N,N-dialkyl aminocarbonyl, N-substituted alkyl aminocarbonyl, N,N-bis-substituted alkyl aminocarbonyl, alkoxy carbonyl, substituted alkoxy carbonyl, halocarbonyl, hydroxymethyl, alkylhydroxymethyl, substituted alkoxymethyl, thiocarboxyl, thioformyl, alkyl thiocarbonyl, substituted alkyl thiocarbonyl, alkenyl thiocarbonyl, substituted alkenyl thiocarbonyl, alkynyl thiocarbonyl, substituted alkynyl thiocarbonyl, aryl thiocarbonyl, substituted aryl thiocarbonyl, heteroaryl thiocarbonyl, substituted heteroaryl thiocarbonyl, arylalkyl thiocarbonyl, arylalkenyl thiocarbonyl, arylalkynyl thiocarbonyl, heteroaralkyl thiocarbonyl, heterocyclyl thiocarbonyl, substituted heterocyclyl thiocarbonyl, thiocarbamyl, N-alkyl thiocarbamyl, N,N-dialkyl thiocarbamyl, N-substituted alkyl thiocarbamyl, N,N-bis-substituted alkyl thiocarbamyl, alkoxy thiocarbonyl, substituted alkoxy thiocarbonyl, halothiocarbonyl, mercaptomethyl, substituted alkylthiomethyl;
• heteroaryl carbonyl, substituted heteroaryl carbonyl, arylalkyl carbonyl, arylalkenyl carbonyl, arylalkynyl carbonyl, heteroaralkyl carbonyl, heterocyclyl carbonyl, substituted heterocyclyl carbonyl, cyano, aminocarbonyl, N-alkyl aminocarbonyl, N,N-dialkyl aminocarbonyl, N-substituted alkyl aminocarbonyl, N,N-bis-substituted alkyl aminocarbonyl, alkoxy carbonyl, substituted alkoxy carbonyl, halocarbonyl, hydroxymethyl, alkoxymethyl, substituted alkoxymethyl;
• T is carbon or nitrogen and can be at any position in the ring;
• R1 is hydrogen, —C1-C8 alkyl-NRaRb, —O—C1-C8 alkyl-NRcRd, —C(O)NReRf or —NRgRh, Ra is a C1-C12 alkyl and Rb is H or a C1-C12 alkyl or Ra and Rb are taken together with the N to which they are attached to form a heterocyclic ring;
• Rc is a C1-C12 alkyl and Rd is H or a C1-C12 alkyl or Rc and Rd are taken together with the N to which they are attached to form a heterocyclic ring;
• Re is H or a C1-C12 alkyl and Rf is H or a C1-C12 alkyl, or Re and Rf are taken together with the N to which they are attached to form a heterocyclic ring;
• Rg is H or a C1-C12 alkyl and Rh is H or a C1-C12 alkyl, or Rg and Rh are taken together with the N to which they are attached to form a heterocyclic ring;
• R2 is hydrogen, halogen, nitro, alkyl or substituted alkyl;
• R4 is H, alkyl, substituted alkyl, aryl or substituted aryl;
• and
• R5 is H, alkyl, substituted alkyl, aryl or substituted aryl.

A method of treating breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein cells of the breast cancer express detectable estrogen receptor but the breast cancer is resistant to endocrine therapy, and wherein the compound is a compound of structural formula (VI):

• wherein:
• X is S or O, and
• when X is S, then R1 is OH or NH2;
• and
• when X is O then R1 is OH, NH or NHMe