Multi-substitued selective androgen receptor modulators and methods of use thereof

A selective androgen receptor modulator compound of formula I:

• wherein X is O;
• 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 F, Cl, Br, I, CH3, CF3, OH, CN, NO2, NHCOCH3, NHCOCF3, NHCOR, alkyl, arylalkyl, OR, NH2, NHR, N(R)2, SR;
• R3 is 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 NHCOCH3;
• n is an integer of 1-4;
• and
• m is an integer of 1-3;
• or its isomer, pharmaceutically acceptable salt, or any combination thereof.

A selective androgen receptor modulator compound represented by the structure of formula II:

• wherein X is O;
• 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;
• R3 is 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;
• n is an integer of 1-4;
• and
• m is an integer of 1-3;
• and
• p is an integer of 2-5;
• or its isomer, pharmaceutically acceptable salt, or any combination thereof.

A selective androgen receptor modulator (SARM) compound represented by the structure of formula V:

• wherein
• R2 is F, Cl, Br, I, CH3, CF3, OH, CN, NO2, NHCOCH3, NHCOCF3, NHCOR, alkyl, arylalkyl, OR, NH2, NHR, N(R)2, SR;
• R3 is 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:
• R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH2F, CHF2, CF3, CF2CF3;
• aryl, phenyl, halogen, alkenyl or OH;
• Z is NO2, CN, COR, COOH, or CONHR;
• Y is CF3, F, Br, Cl, I, CN, or Sn(R)3;
• Q is H, alkyl, halogen, CF3, CN, C(R)3, Sn(R)3, N(R)2, NHCOCH3, NHCOCF3, NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH3, NHCSCF3, NHCSR NHSO2CH3, NHSO2R, OH, OR, COR, OCOR, OSO2R, SO2R, SR;
• n is an integer of 1-4;
• and
• m is an integer of 1-3;
• or its isomer, pharmaceutically acceptable salt, or any combination thereof.

A selective androgen receptor modulator compound of formula V:

• wherein
• R2 is F, Cl, Br, I, CH3, CF3, OH, CN, NO2, NHCOCH3, NHCOCF3, NHCOR, alkyl, arylalkyl, OR, NH2, NHR, N(R)2, SR;
• R3 is 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:
• R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH2F, CHF2, CF3, CF2CF3;
• aryl, phenyl, halogen, alkenyl or OH;
• Z is NO2, CN, COR, COOH, or CONHR;
• Y is CF3, F, Br, Cl, I, CN, or Sn(R)3;
• Q is NHCOCH3,
• n is an integer of 1-4;
• and
• m is an integer of 1-3;
• or its isomer, pharmaceutically acceptable salt, or any combination thereof.

A process for preparing a selective androgen receptor modulator (SARM) compound represented by the structure of formula I, or its isomer, pharmaceutically acceptable salt, or any combination thereof:

• wherein X is O
• 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 F, Cl, Br, I, CH3, CF3, OH, CN, NO2, NHCOCH3, NHCOCF3, NHCOR, alkyl, arylalkyl, OR, NH2, NHR, N(R)2, SR;
• R3 is 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 H, alkyl, halogen, CF3, CN, C(R)3, Sn(R)3, N(R)2, NHCOCH3, NHCOCF3, NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH3, NHCSCF3, NHCSR NHSO2CH3, NHSO2R, OH, OR, COR, OCOR, OSO2R, SO2R, SR;
• n is an integer of 1-4;
• and
• m is an integer of 1-3;
• said process comprising the step of coupling a compound of formula VII:
• wherein Z, Y, G, T, R3 and m are as defined above and L is a leaving group, with a compound of formula VIII:
• wherein Q, X, R2 and n are as defined above.