Selective androgen receptor modulators and methods of use thereof
View Patent ↗This invention provides SARM compounds and their use in treating a variety of diseases or conditions in a subject, including, inter-alia, a muscle wasting disease and/or disorder or a bone-related disease and/or disorder.
1. A method of treating a subject having a bone-related disorder, comprising the step of administering to said subject a SARM compound represented by a structure of formula (I), its pharmaceutically acceptable salt, or a combination thereof, or a composition comprising the same:
wherein
X is O;
Z is NO 2 , CN, COR, or CONHR;
Y is I, CF 3 , Br, Cl, F or Sn(R) 3 ;
Q is CN;
T is OH, OR, —NHCOCH 3 , NHCOR or OC(O)R;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, halogen, alkenyl or OH; and
R 1 is CH 3 , CH 2 F, CHF 2 , CH2CH 3 , or CF 2 CF 3 .
2. The method of claim 1 , wherein said SARM compound is represented by a structure of formula (III), or its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same,
3. The method of claim 1 , wherein said composition further comprises alendronate.
4. A method of increasing the strength of, or mass of a bone of a subject, or in promoting bone formation in a subject, comprising the step of administering to said subject a SARM compound represented by a structure of formula (I), its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same:
wherein
X is O;
Z is NO 2 , CN, COR, or CONHR;
Y is I, CF 3 , Br, Cl, F or Sn(R) 3 ;
Q is CN;
T is OH, OR, —NHCOCH 3 , NHCOR or OC(O)R;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, halogen, alkenyl or OH; and
R 1 is CH 3 , CH 2 F, CHF 2 , CH 2 CH 3 , or CF2CF 3 .
5. The method of claim 4 , wherein said SARM compound is represented by a structure of formula (III), or its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same
6. The method of claim 4 , wherein said composition further comprises alendronate.
7. The method of claim 4 , wherein said subject has sarcopenia or cachexia.
8. The method of claim 4 , wherein said subject has osteoporosis.
9. The method of claim 4 , wherein said osteoporosis is hormonally induced.
10. A method in the intervention of osteoperosois or osteopenia, comprising the step of administering to said subject a SARM compound represented by a structure of formula (I), its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same:
wherein
X is O;
Z is NO 2 , CN, COR, or CONHR;
Y is I, CF 3 , Br, Cl, F or Sn(R) 3 ;
Q is CN;
T is OH, OR, —NHCOCH 3 , NHCOR or OC(O)R;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, halogen, alkenyl or OH; and
R 1 is CH 3 , CH 2 F, CHF 2 , CH 2 CH 3 , or CF 2 CF 3 .
11. The method of claim 10 , wherein said SARM compound is represented by a structure of formula (III), its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same.
12. A method of treating, suppressing, inhibiting or reducing the incidence of a muscle wasting disorder in a subject comprising the step of administering to said subject a SARM compound represented by a structure of formula (I), its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same:
wherein
X is O;
Z is NO 2 , CN, COR, or CONHR;
Y is I, CF 3 , Br, Cl, F or Sn(R) 3 ;
Q is CN;
T is OH, OR, —NHCOCH 3 , NHCOR or OC(O)R;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, halogen, alkenyl or OH; and
R 1 is CH 3 , CH 2 F, CHF 2 , CH 2 CH 3 , or CF 2 CF 3 .
13. The method of claim 12 , wherein said SARM compound is represented by a structure of formula (III), its pharmaceutically acceptable salt, or any combination thereof or a composition comprising the same,
14. The method of claim 12 , wherein said muscle wasting disorder is due to a pathology, illness, disease or condition.
15. A method in increasing muscle performance, muscle size, muscle strength, or any combination thereof in a subject comprising the step of administering to said subject a SARM compound represented by a structure of formula (I), its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same:
wherein
X is O;
Z is NO 2 , CN, COR, or CONHR;
Y is I, CF 3 , Br, Cl, F or Sn(R) 3 ;
Q is CN;
T is OH, OR, —NHCOCH 3 , NHCOR or OC(O)R;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, halogen, alkenyl or OH; and
R 1 is CH 3 , CH 2 F, CHF 2 , CH 2 CH 3 , or CF 2 CF 3 .
16. The method of claim 15 , wherein said SARM compound is represented by a structure of formula (III), its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same,
17. A method in treating obesity or diabetes associated with a metabolic syndrome in a subject comprising the step of administering to said subject a SARM compound represented by a structure of formula (I), its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same:
wherein
X is O;
Z is NO 2 , CN, COR, or CONHR;
Y is I, CF 3 , Br, Cl, F or Sn(R) 3 ;
Q is CN;
T is OH, OR, —NHCOCH 3 , NHCOR or OC(O)R;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, halogen, alkenyl or OH; and
R 1 is CH 3 , CH 2 F, CHF 2 , CH 2 CH 3 , or CF 2 CF 3 .
18. The method of claim 17 , wherein said SARM compound is represented by a structure of formula (III), its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same,
19. The method of claim 17 , wherein said subject has a hormonal imbalance, disorder, or disease.
20. The method of claim 17 , wherein said subject is in menopause.
21. The method of claim 17 , wherein said SARM increases lean mass in the subject.
22. A method in promoting or speeding recovery following a surgical procedure, in a subject comprising the step of administering to said subject a SARM compound represented by a structure of formula (I), its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same:
wherein
X is O;
Z is NO 2 , CN, COR, or CONHR;
Y is I, CF 3 , Br, Cl, F or Sn(R) 3 ;
Q is CN;
T is OH, OR, —NHCOCH 3 , NHCOR or OC(O)R;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, halogen, alkenyl or OH; and
R 1 is CH 3 , CH 2 F, CHF 2 , CH 2 CH 3 , or CF 2 CF 3 .
23. The method of claim 22 , wherein said SARM compound is represented by a structure of formula (III), its pharmaceutically acceptable salt, or any combination thereof, or a composition comprising the same,