Method of treating androgen receptor (ar) -positive breast cancers with selective androgen receptor modulator (sarms)

A method of treating a subject suffering from metastatic AR-positive breast cancer, or advanced AR-positive breast cancer comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound represented by a structure of formula I:

• X is a bond, O, CH2, NH, S, Se, PR, NO or NR;
• G is O or S;
• T is OH, OR, —NHCOCH3, or NHCOR;
• R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH2F, CHF2, CF3, CF2CF3, aryl, phenyl, halogen, alkenyl or OH;
• R1 is CH3, CH2F, CHF2, CF3, CH2CH3, or CF2CF3;
• R2 is H, F, Cl, Br, I, CH3, CF3, OH, CN, NO2, NHCOCH3, NHCOCF3, NHCOR, alkyl, arylalkyl, OR, NH2, NHR, N(R)2, SR;
• R3 is H, F, Cl, Br, I, CN, NO2, COR, COOH, CONHR, CF3, Sn(R)3, or R3 together with the benzene ring to which it is attached forms a fused ring system represented by the structure:
• Z is NO2, CN, COR, COOH, or CONHR;
• Y is CF3, F, Br, Cl, I, CN, or Sn(R)3;
• Q is CN, alkyl, halogen, N(R)2, NHCOCH3, NHCOCF3, NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH3, NHCSCF3, NHCSR, NHSO2CH3, NHSO2R, OR, COR, OCOR, OSO2R, SO2R or SR;
• or Q together with the benzene ring to which it is attached is a fused ring system represented by structure A, B or C:
• n is an integer of 1-4;
• and
• m is an integer of 1-3.

A method of treating a subject suffering from refractory AR-positive breast cancer, comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound represented by a structure of formula I:

• X is a bond, O, CH2, NH, S, Se, PR, NO or NR;
• G is O or S;
• T is OH, OR, —NHCOCH3, or NHCOR;
• R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH2F, CHF2, CF3, CF2CF3, aryl, phenyl, halogen, alkenyl or OH;
• R1 is CH3, CH2F, CHF2, CF3, CH2CH3, or CF2CF3;
• R2 is H, F, Cl, Br, I, CH3, CF3, OH, CN, NO2, NHCOCH3, NHCOCF3, NHCOR, alkyl, arylalkyl, OR, NH2, NHR, N(R)2, SR;
• R3 is H, F, Cl, Br, I, CN, NO2, COR, COOH, CONHR, CF3, Sn(R)3, or R3 together with the benzene ring to which it is attached forms a fused ring system represented by the structure:
• Z is NO2, CN, COR, COOH, or CONHR;
• Y is CF3, F, Br, Cl, I, CN, or Sn(R)3;
• Q is CN, alkyl, halogen, N(R)2, NHCOCH3, NHCOCF3, NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH3, NHCSCF3, NHCSR, NHSO2CH3, NHSO2R, OR, COR, OCOR, OSO2R, SO2R or SR;
• or Q together with the benzene ring to which it is attached is a fused ring system represented by structure A, B or C:
• n is an integer of 1-4;
• and
• m is an integer of 1-3.

A method of treating, preventing, suppressing or inhibiting metastasis in a subject suffering from breast cancer, comprising the step of administering to said subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound represented by a structure of formula I:

• X is a bond, O, CH2, NH, S, Se, PR, NO or NR;
• G is O or S;
• T is OH, OR, —NHCOCH3, or NHCOR;
• R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH2F, CHF2, CF3, CF2CF3, aryl, phenyl, halogen, alkenyl or OH;
• R1 is CH3, CH2F, CHF2, CF3, CH2CH3, or CF2CF3;
• R2 is H, F, Cl, Br, I, CH3, CF3, OH, CN, NO2, NHCOCH3, NHCOCF3, NHCOR, alkyl, arylalkyl, OR, NH2, NHR, N(R)2, SR;
• R3 is H, F, Cl, Br, I, CN, NO2, COR, COOH, CONHR, CF3, Sn(R)3, or R3 together with the benzene ring to which it is attached forms a fused ring system represented by the structure:
• Z is NO2, CN, COR, COOH, or CONHR;
• Y is CF3, F, Br, Cl, I, CN, or Sn(R)3;
• Q is CN, alkyl, halogen, N(R)2, NHCOCH3, NHCOCF3, NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH3, NHCSCF3, NHCSR, NHSO2CH3, NHSO2R, OR, COR, OCOR, OSO2R, SO2R or SR;
• or Q together with the benzene ring to which it is attached is a fused ring system represented by structure A, B or C:
• n is an integer of 1-4;
• and
• m is an integer of 1-3.

A method of prolonging progression-free survival of a subject suffering from breast cancer comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound represented by a structure of formula I:

• X is a bond, O, CH2, NH, S, Se, PR, NO or NR;
• G is O or S;
• T is OH, OR, —NHCOCH3, or NHCOR;
• R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH2F, CHF2, CF3, CF2CF3, aryl, phenyl, halogen, alkenyl or OH;
• R1 is CH3, CH2F, CHF2, CF3, CH2CH3, or CF2CF3;
• R2 is H, F, Cl, Br, I, CH3, CF3, OH, CN, NO2, NHCOCH3, NHCOCF3, NHCOR, alkyl, arylalkyl, OR, NH2, NHR, N(R)2, SR;
• R3 is H, F, Cl, Br, I, CN, NO2, COR, COOH, CONHR, CF3, Sn(R)3, or R3 together with the benzene ring to which it is attached forms a fused ring system represented by the structure:
• Z is NO2, CN, COR, COOH, or CONHR;
• Y is CF3, F, Br, Cl, I, CN, or Sn(R)3;
• Q is CN, alkyl, halogen, N(R)2, NHCOCH3, NHCOCF3, NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH3, NHCSCF3, NHCSR, NHSO2CH3, NHSO2R, OR, COR, OCOR, OSO2R, SO2R or SR;
• or Q together with the benzene ring to which it is attached is a fused ring system represented by structure A, B or C:
• n is an integer of 1-4;
• and
• m is an integer of 1-3.