Treating androgen decline in aging male (ADAM)-associated conditions with SARMs

Patent metadata

Field	Value
Publication number	US-9493403-B2
Application number	US-201313899239-A
Country	US
Kind code	B2
Filing date	May 21, 2013
Priority date	Aug 24, 2000
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

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.

First claim

What is claimed is:

1. A method of treating 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, said method comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound represented by the structure of formula V:

wherein
R 2 is F, Cl, Br, I, CH 3 , CF 3 , OH, CN, NO 2 , NHCOCH 3 , NHCOCF 3 , NHCOR, alkyl, arylalkyl, OR, NH 2 , NHR, N(R) 2 or SR;
R 3 is H, F, Cl, Br, I, CN, NO 2 , COR, COOH, CONHR, CF 3 , or Sn(R) 3 ;
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;
Z is NO 2 , CN, COR, COOH, or CONHR;
Y is CF 3 , F, Br, Cl, I, CN, 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, OH, OR, COR, OCOR, OSO 2 R, SO 2 R, SR, NCS, SCN, NCO, or OCN;
n is an integer of 1-4; and
m is an integer of 1-3,

or its optical isomer or pharmaceutically acceptable salt, or any combination thereof.

2. The method of claim 1 , wherein said Z is CN.

3. The method of claim 1 , wherein said Q is halogen.

4. The method of claim 1 , wherein said SARM does not penetrate the central nervous system (CNS).

5. 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.

6. The method according to claim 5 , 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.

7. The method according to claim 5 , 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.

8. The method of claim 1 , wherein said male subject is an aging male subject.

9. 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, said method comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound represented by the structure of formula V:

R 2 is F, Cl, Br, I, CH 3 , CF 3 , OH, CN, NO 2 , NHCOCH 3 , NHCOCF 3 , NHCOR, alkyl, arylalkyl, OR, NH 2 , NHR, N(R) 2 or SR;
R 3 is H, F, Cl, Br, I, CN, NO 2 , COR, COOH, CONHR, CF 3 , or Sn(R) 3 ;
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;
Z is NO 2 , CN, COR, COOH, or CONHR;
Y is CF 3 , F, Br, Cl, I, CN, 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, OH, OR, COR, OCOR, OSO 2 R, SO 2 R, SR, NCS, SCN, NCO, or OCN;
n is an integer of 1-4; and
m is an integer of 1-3,

or its optical isomer or pharmaceutically acceptable salt, or any combination thereof.

10. The method of claim 9 , wherein said Z is CN.

11. The method of claim 9 , wherein said Q is halogen.

12. The method of claim 9 , wherein said SARM does not penetrate the central nervous system (CNS).

13. The method of claim 9 , 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.

14. The method according to claim 9 , 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.

15. The method according to claim 14 , 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.

16. The method of claim 9 , wherein said male subject is an aging male subject.

Assignees

• Univ Tennessee Res Found

Inventors

• Dalton James T
• Miller Duane D
• Yin Donghua
• He Yali

Classifications

• A61K31/16

  Amides, e.g. hydroxamic acids · CPC title

• C07C255/60

  at least one of the singly-bound nitrogen atoms being acylated · CPC title

• C07C235/24 Primary

  having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring · CPC title

• A61P5/26

  Androgens · CPC title

• A61K31/277

  having a ring, e.g. verapamil · CPC title