SELECTIVE ANDROGEN RECEPTOR MODULATORS FOR TREATING DIABETES
This invention provides use of a SARM compound or a composition comprising the same in treating and preventing muscle wasting in patients with non-small cell lung cancer (NSCLC); treating pre-cachexia or early cachexia (preventing muscle wasting in a cancer patient); treating and preventing loss of physical function due to cancer or cancer therapy; increase of physical function; and increasing survival in a patient with NSCLC.
1 . A method of treating, reducing the severity of, reducing the incidence of, delaying the onset of, or reducing pathogenesis of muscle wasting in a human subject with non-small cell lung cancer, comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound of formula II:
wherein
X is O;
Z is a hydrogen bond acceptor, NO 2 , CN, COR, CONHR;
Y is a lipid soluble group, CF 3 , CH 3 , formyl, alkoxy, H, F, I, Br, Cl, Sn(R) 3 ;
R is an alkyl, aryl, phenyl, alkenyl, haloalkyl, haloalkenyl, halogen or OH;
and
Q is alkyl, halogen, N(R) 2 , CN, NHCOCH 3 , NHCOCF 3 , NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH 3 , NHCSCF 3 , NHCSRNHSO 2 CH 3 , NHSO 2 R, OR, COR, OCOR, OSO 2 R, SO 2 R or SR, acetamido-, trifluoroacetamido-, alkylamines, ether, alkyl, N-sulfonyl, O-sulfonyl, alkylsulfonyl, carbonyl, or a ketone.
2 . The method of claim 1 , wherein said compound is characterized by the structure of formula III:
3 . The method of claim 1 , wherein said administering comprises administering a pharmaceutical composition comprising said compound and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.
4 . The method of claim 1 , wherein said method further increases the physical function of said subject with non-small cell lung cancer.
5 . The method of claim 4 , wherein said method further increases the quality of life of said subject with non-small cell lung cancer.
6 . The method of claim 1 , wherein said method increases the survival of said subject.
7 . A method of treating, reducing the severity of, reducing the incidence of, delaying the onset of, or reducing pathogenesis of cachexia, pre-cachexia or early cachexia in a subject with non-small cell lung cancer, comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound of formula II:
wherein
X is O;
Z is a hydrogen bond acceptor, NO 2 , CN, COR, CONHR;
Y is a lipid soluble group, CF 3 , CH 3 , formyl, alkoxy, H, F, I, Br, Cl, Sn(R) 3 ;
R is an alkyl, aryl, phenyl, alkenyl, haloalkyl, haloalkenyl, halogen or OH;
and
Q is alkyl, halogen, N(R) 2 , CN, NHCOCH 3 , NHCOCF 3 , NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH 3 , NHCSCF 3 , NHCSRNHSO 2 CH 3 , NHSO 2 R, OR, COR, OCOR, OSO 2 R, SO 2 R or SR, acetamido-, trifluoroacetamido-, alkylamines, ether, alkyl, N-sulfonyl, O-sulfonyl, alkylsulfonyl, carbonyl, or a ketone.
8 . The method of claim 7 , wherein said compound is characterized by the structure of formula III:
9 . The method of claim 7 , wherein said administering comprises administering a pharmaceutical composition comprising said compound and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.
10 . The method of claim 7 , wherein said method further increases the physical function of said subject.
11 . The method of claim 10 , wherein said method further increases the quality of life of said subject.
12 . The method of claim 7 , wherein said method increases the survival of said subject.
13 . A method of treating, reducing the severity of, reducing the incidence of, delaying the onset of, or reducing pathogenesis of pre-cachexia or early cachexia in a subject suffering from cancer, comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound of formula II:
wherein
X is O;
Z is a hydrogen bond acceptor, NO 2 , CN, COR, CONHR;
Y is a lipid soluble group, CF 3 , CH 3 , formyl, alkoxy, H, F, I, Br, Cl, Sn(R) 3 ;
R is an alkyl, aryl, phenyl, alkenyl, haloalkyl, haloalkenyl, halogen or OH;
and
Q is alkyl, halogen, N(R) 2 , CN, NHCOCH 3 , NHCOCF 3 , NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH 3 , NHCSCF 3 , NHCSRNHSO 2 CH 3 , NHSO 2 R, OR, COR, OCOR, OSO 2 R, SO 2 R or SR, acetamido-, trifluoroacetamido-, alkylamines, ether, alkyl, N-sulfonyl, O-sulfonyl, alkylsulfonyl, carbonyl, or a ketone.
14 . The method of claim 13 , wherein said compound is characterized by the structure of formula III:
15 . The method of claim 13 , wherein said administering comprises administering a pharmaceutical composition comprising said compound and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.
16 . The method of claim 13 , wherein said method further increases the physical function of said subject.
17 . The method of claim 16 , wherein said method further increases the quality of life of said subject.
18 . The method of claim 13 , wherein said method increases the survival of said subject.
19 . A method of treating, reducing the severity of, reducing the incidence of, delaying the onset of, loss of physical function in a subject suffering from cancer, comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound of formula II:
wherein
X is O;
Z is a hydrogen bond acceptor, NO 2 , CN, COR, CONHR;
Y is a lipid soluble group, CF 3 , CH 3 , formyl, alkoxy, H, F, I, Br, Cl, Sn(R) 3 ;
R is an alkyl, aryl, phenyl, alkenyl, haloalkyl, haloalkenyl, halogen or OH;
and
Q is alkyl, halogen, N(R) 2 , CN, NHCOCH 3 , NHCOCF 3 , NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH 3 , NHCSCF 3 , NHCSRNHSO 2 CH 3 , NHSO 2 R, OR, COR, OCOR, OSO 2 R, SO 2 R or SR, acetamido-, trifluoroacetamido-, alkylamines, ether, alkyl, N-sulfonyl, O-sulfonyl, alkylsulfonyl, carbonyl, or a ketone.
20 . The method of claim 19 , wherein said compound is characterized by the structure of formula III:
21 . The method of claim 19 , wherein said administering comprises administering a pharmaceutical composition comprising said compound and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.
22 . The method of claim 19 , wherein said method further increases the physical function of said subject.
23 . The method of claim 19 , wherein said method further increases the quality of life of said subject.
24 . The method of claim 19 , wherein said cancer is non-small cell lung cancer, colon cancer, breast cancer, non-Hodgkin's lymphoma, chronic lymphocytic leukemia or lung cancer.
25 . The method of claim 19 , wherein said method increases the survival of said subject.
26 . A method of increasing the survival of a human subject with non-small cell lung cancer, comprising the step of administering to said subject a selective androgen receptor modulator (SARM) compound of formula II:
wherein
X is O;
Z is a hydrogen bond acceptor, NO 2 , CN, COR, CONHR;
Y is a lipid soluble group, CF 3 , CH 3 , formyl, alkoxy, H, F, I, Br, Cl, Sn(R) 3 ;
R is an alkyl, aryl, phenyl, alkenyl, haloalkyl, haloalkenyl, halogen or OH;
and
Q is alkyl, halogen, N(R) 2 , CN, NHCOCH 3 , NHCOCF 3 , NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH 3 , NHCSCF 3 , NHCSRNHSO 2 CH 3 , NHSO 2 R, OR, COR, OCOR, OSO 2 R, SO 2 R or SR, acetamido-, trifluoroacetamido-, alkylamines, ether, alkyl, N-sulfonyl, O-sulfonyl, alkylsulfonyl, carbonyl, or a ketone.
27 . The method of claim 26 , wherein said compound is characterized by the structure of formula III:
28 . The method of claim 26 , wherein said administering comprises administering a pharmaceutical composition comprising said compound and/or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof; and a pharmaceutically acceptable carrier.