Treating androgen decline in aging male (ADAM)-associated conditions with SARMs
This invention provides methods for treatment and inhibition of a male subject having an Androgen Decline in Aging Male (ADAM)-associated condition, for example sexual dysfunction, decreased sexual libido, erectile dysfunction, hypogonadism, sarcopenia, osteopenia, osteoporosis, an alteration in cognition and mood, depression, anemia, hair loss, obesity, muscle loss, dry eye, memory loss, benign prostate hyperplasia and/or prostate cancer, by administering to the subject a selective androgen receptor modulator (SARM) compound and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, pro-drug, polymorph, crystal, or any combination thereof.
1. A method of treating a male subject suffering from an Androgen Decline in Aging Male (ADAM)-associated condition, wherein said ADAM-associated condition is selected from the group consisting of fatigue, depression, decreased libido, sexual dysfunction, erectile dysfunction, hypogonadism, osteoporosis, hair loss, anemia, obesity, sarcopenia, osteopenia, benign prostate hyperplasia, alterations in mood and cognition and prostate cancer, said method comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound represented by the structure of formula I:
wherein G is O or S;
X is O;
T is OH, OR, —NHCOCH 3 , or NHCOR;
Z is NO 2 , CN, COOH, COR, NHCOR or CONHR;
Y is CF 3 , F, I, Br, Cl, CN, C(R) 3 or Sn(R) 3 ;
Q is alkyl, F, Cl, Br, I, CF 3 , CN, C(R) 3 , Sn(R) 3 , 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, SR, NCS, SCN, NCO, OCN;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, F, Cl, Br, I, alkenyl or OH; and
R 1 is CH 3 , CH 2 F, CHF 2 , CF 3 , CH 2 CH 3 , or CF 2 CF 3 ;
or its optical isomer or pharmaceutically acceptable salt, or any combination thereof.
2. The method according to claim 1 , wherein said SARM compound is represented by the structure of formula II:
wherein X is O;
Z is NO 2 , CN, COOH, COR, NHCOR or CONHR;
Y is CF 3 , F, I, Br, Cl, CN, C(R) 3 or Sn(R) 3 ;
Q is alkyl, F, Cl, Br, I, CF 3 , CN, C(R) 3 , Sn(R) 3 , 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, SR, NCS, SCN, NCO, OCN;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, F, Cl, Br, I, alkenyl or OH.
3. The method of claim 1 , wherein said Z is CN.
4. The method of claim 1 , wherein said Q is halogen.
5. The method according to claim 1 , wherein said SARM compound is represented by the structure of formula 6:
6. The method of claim 1 , wherein said SARM does not penetrate the central nervous system (CNS).
7. The method of claim 1 , further comprising administering a pharmaceutical preparation comprising said SARM compound and/or its optical isomer or pharmaceutically acceptable salt or any combination thereof; and a pharmaceutically acceptable carrier.
8. The method according to claim 7 , comprising intravenously, intraarterially, or intramuscularly injecting to said subject said pharmaceutical preparation in liquid form; subcutaneously implanting in said subject a pellet containing said pharmaceutical preparation; orally administering to said subject said pharmaceutical preparation in a liquid or solid form; or topically applying to the skin surface of said subject said pharmaceutical preparation.
9. The method according to claim 7 , wherein said pharmaceutical preparation is a pellet, a tablet, a capsule, a solution, a suspension, an emulsion, an elixir, a gel, a cream, a suppository or a parenteral formulation.
10. The method of claim 1 , wherein said male subject is an aging male subject.
11. A method of suppressing, inhibiting or reducing the incidence of an Androgen Decline in Aging Male (ADAM)-associated condition in a male subject, wherein said ADAM-associated condition is selected from the group consisting of fatigue, depression, decreased libido, sexual dysfunction, erectile dysfunction, hypogonadism, osteoporosis, hair loss, anemia, obesity, sarcopenia, osteopenia, benign prostate hyperplasia, alterations in mood and cognition and prostate cancer, said method comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound represented by the structure of formula I:
wherein G is O or S;
X is O;
T is OH, OR, —NHCOCH 3 , or NHCOR;
Z is NO 2 , CN, COOH, COR, NHCOR or CONHR;
Y is CF 3 , F, I, Br, Cl, CN, C(R) 3 or Sn(R) 3 ;
Q is alkyl, F, Cl, Br, I, CF 3 , CN, C(R) 3 , Sn(R) 3 , 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, SR, NCS, SCN, NCO, OCN;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, F, Cl, Br, I, alkenyl or OH; and
R 1 is CH 3 , CH 2 F, CHF 2 , CF 3 , CH 2 CH 3 , or CF 2 CF 3 ;
or its optical isomer or pharmaceutically acceptable salt, or any combination thereof.
12. The method according to claim 11 , wherein said SARM compound is represented by the structure of formula II;
wherein X is O;
Z is NO 2 , CN, COOH, COR, NHCOR or CONHR;
Y is CF 3 , F, I, Br, Cl, CN, C(R) 3 or Sn(R) 3 ;
Q is alkyl, F, Cl, Br, I, CF 3 , CN, C(R) 3 , Sn(R) 3 , 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, SR, NCS, SCN, NCO, OCN;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, F, Cl, Br, I, alkenyl or OH.
13. The method of claim 11 , wherein said Z is CN.
14. The method of claim 11 , wherein said Q is halogen.
15. The method according to claim 11 , wherein said SARM compound is represented by the structure of formula 6:
16. The method of claim 11 , wherein said SARM does not penetrate the central nervous system (CNS).
17. The method of claim 11 , further comprising administering a pharmaceutical preparation comprising said SARM compound and/or its optical isomer or pharmaceutically acceptable salt, or any combination thereof; and a pharmaceutically acceptable carrier.
18. The method according to claim 17 , comprising intravenously, intraarterially, or intramuscularly injecting to said subject said pharmaceutical preparation in liquid form; subcutaneously implanting in said subject a pellet containing said pharmaceutical preparation; orally administering to said subject said pharmaceutical preparation in a liquid or solid form; or topically applying to the skin surface of said subject said pharmaceutical preparation.
19. The method according to claim 17 , wherein said pharmaceutical preparation is a pellet, a tablet, a capsule, a solution, a suspension, an emulsion, an elixir, a gel, or a cream.
20. The method of claim 11 , wherein said male subject is an aging male subject.