Selective androgen receptor modulators for treating muscle wasting

1 . A method of treating a human subject having a muscle wasting disorder, comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound of formula III:

or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof.

2 . The method of claim 1 , wherein said administering comprises administering a pharmaceutical composition comprising said SARM and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.

3 . A method of treating a human subject having a muscle wasting disorder, comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound of formula I:

wherein X is O, CH 2 , NH, Se, PR, or NR;

Z is NO 2 , CN, COR, or CONHR;

Y is I, CF 3 , CH 3 , H, Br, Cl, F or Sn(R) 3 ;

Q is CN, alkyl, F, Cl, Br, I, N(R) 2 , NHCOCH 3 , NHCOCF 3 , NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH 3 , NHCSCF 3 , NHCSR NHSO 2 CH 3 , NHSO 2 R, OR, COR, OCOR, OSO 2 R, SO 2 R 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:

R 1 is CH 3 , CF 3 , CH 2 CH 3 , or CF 2 CF 3 : and

T is OH, OR, —NHCOCH 3 , or NHCOR;

wherein R is a C 1 -C 4 alkyl, aryl, phenyl, alkenyl, hydroxyl, a C 1 -C 4 haloalkyl, halogen, or haloalkenyl:

or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof.

4 . The method of claim 3 , wherein said administering comprises administering a pharmaceutical composition comprising said SARM and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.

5 . The method of claim 3 , wherein said SARM compound is represented by the structure of formula II:

wherein X is O;

Z is NO 2 , CN, COR, or CONHR;

Y is I, CF 3 , CH 3 , H, Br, Cl, F or Sn(R) 3 ;

R is an alkyl, aryl, phenyl, alkenyl, haloalkyl, haloalkenyl, halogen or OH; and

Q is CN.

6 . The method of claim 3 , wherein said SARM compound is of formula I:

wherein X is O;

Z is NO 2 , CN, COR, COOH or CONHR;

Y is I, CF 3 , CH 3 , H, Br, Cl, or Sn(R) 3 ;

Q is CN,

R 1 is CH 3 , CF 3 , CH 2 CH 3 , or CF 2 CF 3 , and

T is OH, OR, —NHCOCH 3 , or NHCOR;

wherein R is a C 1 -C 4 alkyl, aryl, phenyl, alkenyl, hydroxyl, a C 1 -C 4 haloalkyl, halogen, or haloalkenyl;

or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof.

7 . The method of claim 6 , wherein said administering comprises administering a pharmaceutical composition comprising said SARM and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.

8 . The method according to claim 6 , wherein X is O.

9 . The method according to claim 6 , wherein Y is CF 3 .

10 . The method according to claim 6 , wherein Z is NO 2 .

11 . The method according to claim 6 , wherein Z is CN.

12 . The method according to claim 6 , wherein Q is CN.

13 . A method of treating a human subject having Cachexia, comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound of formula III:

or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof.

14 . The method of claim 1 , wherein said administering comprises administering a pharmaceutical composition comprising said SARM and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.

15 . A method of treating a human subject having Cachexia, comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound of formula I:

wherein X is O, CH 2 , NH, Se, PR, or NR;

Z is NO 2 , CN, COR, or CONHR;

Y is I, CF 3 , CH 3 , H, Br, Cl, F or Sn(R) 3 ;

Q is CN, alkyl, F, Cl, Br, I, N(R) 2 , NHCOCH 3 , NHCOCF 3 , NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH 3 , NHCSCF 3 , NHCSR, NHSO 2 CH 3 , NHSO 2 R, OR, COR, OCOR, OSO 2 R, SO 2 R 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:

R 1 is CH 3 , CF 3 , CH 2 CH 3 , or CF 2 CF 3 : and

T is OH, OR, —NHCOCH 3 , or NHCOR;

wherein R is a C 1 -C 4 alkyl, aryl, phenyl, alkenyl, hydroxyl, a C 1 -C 4 haloalkyl, halogen, or haloalkenyl;

or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof.

16 . The method of claim 15 , wherein said administering comprises administering a pharmaceutical composition comprising said SARM and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.

17 . The method of claim 15 , wherein said SARM compound is represented by the structure of formula II:

wherein X is O;

Z is NO 2 , CN, C(O)R, or CONHR;

Y is I, CF 3 , CH 3 , H, Br, Cl, F or Sn(R) 3 ;

R is an alkyl, aryl, phenyl, alkenyl, haloalkyl, haloalkenyl, halogen or OH; and

Q is CN.

18 . The method of claim 15 , wherein said SARM compound is of formula I:

wherein X is O;

Z is NO 2 , CN, COR, COOH or CONHR;

Y is I, CF 3 , CH 3 , H, Br, Cl, or Sn(R) 3 ;

Q is CN,

R 1 is CH 3 , CF 3 , CH 2 CH 3 , or CF 2 CF 3 ; and

T is OH, OR, —NHCOCH 3 , or NHCOR;

wherein R is a C 1 -C 4 alkyl, aryl, phenyl, alkenyl, hydroxyl, a C 1 -C 4 haloalkyl, halogen, or haloalkenyl;

or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof.

19 . The method of claim 18 , wherein said administering comprises administering a pharmaceutical composition comprising said SARM and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.

20 . The method according to claim 18 , wherein X is O.

21 . The method according to claim 18 , wherein Y is CF 3 .

22 . The method according to claim 18 , wherein Z is NO 2 .

23 . The method according to claim 18 , wherein Z is CN.

24 . The method according to claim 18 , wherein Q is CN.

25 - 60 . (canceled)

61 . A method of improving the lipid profile in a human subject, comprising the step of administering to said subject a selective androgen receptor modulator compound of formula III:

or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof.

62 . The method of claim 61 , wherein said administering comprises administering a pharmaceutical composition comprising said SARM and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.

63 . A method of improving the lipid profile in a human subject, comprising the step of administering to said subject a selective androgen receptor modulator compound of formula I:

wherein X is O, C 2 , Se, PR, or NR;

Z is NO 2 , CN, COR, or CONHR;

Y is I, CF 3 , CH 3 , H, Br, Cl, F or Sn(R) 3 ;

Q is CN, alkyl, F, Cl Br, I, N(R) 2 , NHCOCH 3 , NHCOCF 3 , NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH 3 , NHCSCF 3 , NHCSR NHSO 2 CH 3 , NHSO 2 R, OR, COR, OCOR, OSO 2 R, SO 2 R or SR;

or Q together with the benzene ring to which it is attached is a fused ring system represented A, B or C:

R 1 is CH 3 , CF 3 , CH 2 CH 3 , or CF 9 CF 3 ; and

T is OH, OR, —NHCOCH 3 , or NHCOR;

wherein R is a C 1 -C 4 alkyl, aryl, phenyl, alkenyl, hydroxyl, a C 1 -C 4 haloalkyl, halogen, or haloalkenyl;

or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof.

64 . The method of claim 63 wherein said administering comprises administering a pharmaceutical composition comprising said SARM and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.

65 . The method of claim 63 , wherein said SARM compound is represented by the structure of formula II:

wherein X is O;

Z is NO 2 , CN, COR, or CONHR,

Y is I, CF 3 , CH 3 , H, Br, Cl, F or Sn(R) 3 ;

R is an alkyl, aryl, phenyl, alkenyl, haloalkyl, haloalkenyl, halogen or OH; and

Q is CN.

66 . The method of claim 63 , wherein said SARM compound is of formula I:

wherein X is O;

Z is NO 2 , CN, COR, COOH or CONHR;

Y is I, CF 3 , CH 3 , H, Br, Cl, or Sn(R) 3 ;

Q is CN,

R 1 is CH 3 , CF 3 , CH 2 CH 3 , or CF 2 CF 3 ; and

T is OH, OR, —NHCOCH 3 , or NHCOR;

wherein R is a C 1 -C 4 alkyl, aryl, phenyl, alkonyl, hydroxyl, a C 1 -C 4 haloalkyl, halogen, or haloalkenyl;

or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof.

67 . The method of claim 66 , wherein said administering comprises administering a pharmaceutical composition comprising said SARM and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.

68 . The method according to claim 66 , wherein X is O.

69 . The method according to claim 66 , wherein Y is CF 3 .

70 . The method according to claim 66 , wherein Z is NO 2 .

71 . The method according to claim 66 , wherein Z is ON.