Estrogen receptor ligands and methods of use thereof

A method of treating, suppressing, reducing the incidence, reducing the severity, or inhibiting the progression of castration-resistant prostate cancer (CRPC) and its symptoms 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, and an anti-androgen, wherein said compound of formula I has the formula:

• wherein
• Y is C(O) or CH2;
• R1 and R2 are independently hydrogen, halogen, hydroxyl, alkoxy, cyano, nitro, CF3, N(R)2, sulfonamide, SO2R, alkyl, haloalkyl, or aryl;
• R3 and R4 are 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, phenyl, halogen, alkenyl, CN, NO2, or OH;
• and
• j and k are independently 1-4.