| 摘要 |
The present invention relates to methods for reducing testosterone levels in a male subject and methods of treating, suppressing, reducing the incidence, reducing the severity, or inhibiting prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC), metastatic castration resistant prostate cancer (mCRPC), and methods of reducing high or increasing PSA levels and/or increasing SHBG levels in a subject suffering from prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC) and metastatic castration resistant prostate cancer (mCRPC). The compounds of this invention suppress free or total testosterone levels despite castrate levels secondary to ADT and reduce high or increasing PSA levels. This reduction in testosterone levels may be used to treat prostate cancer, advanced prostate cancer, CRPC and mCRPC without causing bone loss, decreased bone mineral density, increased risk of bone fractures, increased body fat, hot flashes and/or gynecomastia. |
| 主权项 |
1. A method of treating, suppressing, reducing the incidence of, reducing the severity of, or inhibiting the progression of castration resistant prostate cancer (CRPC) and its symptoms, or increasing the overall or progression-free survival of men with castration resistant prostate cancer (CRPC) comprising administering a therapeutically effective amount of a compound of formula I, or its isomer, pharmaceutically acceptable salt, pharmaceutical product, polymorph, hydrate or any combination thereof:wherein
Y is C(O) or CH2; R1 and R2 are each independently hydrogen, halogen, hydroxyl, alkoxy, cyano, nitro, CF3, N(R)2, sulfonamide, SO2R, alkyl, haloalkyl, aryl, O-Alk-NR5R6 or O-Alk-heterocycle in which the heterocycle is a 3-7 membered substituted or unsubstituted heterocyclic ring, optionally aromatic; R3 and R4 are each independently hydrogen, halogen, hydroxyalkyl, hydroxyl, alkoxy, cyano, nitro, CF3, NHCOR, N(R)2, sulfonamide, SO2R, alkyl, haloalkyl, aryl or protected hydroxyl; R is alkyl, hydrogen, haloalkyl, dihaloalkyl, trihaloalkyl, CH2F, CHF2, CF3, CF2CF3, aryl, halogen, alkenyl, CN, NO2, or OH; R5 and R6 are independently hydrogen, phenyl, an alkyl group of 1 to 6 carbon atoms, a 3 to 7 membered cycloalkyl, a 3 to 7 membered heterocycle, or a 5 to 7 membered aryl; or R5 and R6 form a 3 to 7 membered ring with the nitrogen atom to which they are attached; j and k are each independently 1-4; and Alk is a linear alkyl of 1-7 carbons, a branched alkyl of 1-7 carbons, or a cyclic alkyl of 3-8 carbons. |
