Chroman-Derived Anti-Androgens For Treatment of Androgen-Mediated Disorders

Abstract

Methods for the prevention and/or alleviation of androgen-mediated disorders by administering a chroman-derived anti-androgen compound are provided by the present invention. The invention further provides pharmaceutical and nutraceutical compositions containing chroman-derived anti-androgen compounds useful in the prevention and/or alleviation of androgen-mediated disorders, particularly prostate cancer.

1 . A method for inhibiting the growth of androgen-dependent tumor cells comprising the step of contacting said tumor cells with an effective amount of:
 (a) a compound having the formula:   
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9  and R 10  are independently a substituted or un-substituted C 1 -C 3  alkyl group or H; R 8  is an OH; or 
       (b) a pharmaceutically acceptable salt of said compound. 
     
   
   
       2 . A method according to  claim 1  wherein said compound has the formula: 
     
       
         
         
             
             
         
       
     
   
   
       3 . A method according to  claim 1  wherein said compound is characterized by a water solubility greater than that of vitamin E. 
   
   
       4 . A method according to  claim 1  wherein said androgen-dependent tumor cells are contained within a patient. 
   
   
       5 . A method of delaying the progression of prostate cancer in a patient suffering from prostate cancer, comprising the step of administering to said patient an effective amount of:
 (a) an anti-androgen compound having the structure:   
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9  and R 10  are independently a substituted or un-substituted C 1 -C 3  alkyl group or H; R 8  is an OH; or 
       (b) a pharmaceutically acceptable salt of said compound. 
     
   
   
       6 . .A method according to  claim 5  wherein said compound is characterized by a water solubility greater than that of vitamin E. 
   
   
       7 . A method of reducing the occurrences or recurrence of prostate cancer in a patient in risk thereof, comprising the step of administering to said patient an effective amount of:
 (a) an anti-androgen compound having the structure:   
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9  and R 10  are independently a substituted or un-substituted C 1 -C 3  alkyl group or H; R 8  is an OH; or 
       (b) a pharmaceutically acceptable salt of said compound. 
     
   
   
       8 . A method according to  claim 7  wherein said compound is characterized by a water solubility greater than that of vitamin E. 
   
   
       9 . A method for the treatment in a patient of an androgen-mediated disorder remediable by contacting an anti-androgen compound with an androgen receptor, comprising the step of administering to the patient an effective amount of:
 (a) an anti-androgen compound having the formula:   
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9  and R 10  are independently a substituted or un-substituted C 1 -C 3  alkyl group or H; R 8  is an OH; or 
       (b) a pharmaceutically acceptable salt of said compound. 
     
   
   
       10 . A method according to  claim 9  wherein said compound reversibly binds to and is an antagonist of the androgen receptor. 
   
   
       11 . A method according to  claim 9  wherein said condition is selected from the group consisting of hirsutism, acne, seborrhea, Alzheimer's disease, androgenic alopecia, hyperpilosity, benign prostatic hypertrophy, adenomas or neoplasias of the prostate, treatment of benign or malignant tumor cells containing the androgen receptor, modulation of VEGF expression for use as antiangiogenic agents, osteoporosis, suppressing spermatogenesis, libido, cachexia, endometriosis, polycystic ovary syndrome, anorexia, androgen-related diseases and conditions, male and female sexual dysfunction and infertility. 
   
   
       12 . A method according to  claim 11  wherein said condition is a neoplasia of the prostate. 
   
   
       13 . A method according to  claim 9  wherein said compound has the formula: 
     
       
         
         
             
             
         
       
     
   
   
       14 . A method according to  claim 9  wherein said compound is characterized by a water solubility greater than that of vitamin E. 
   
   
       15 . A pharmaceutical composition comprising:
 (a) a compound having the formula:   
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9  and R 10  are independently a substituted or un-substituted C 1 -C 3  alkyl group or H; R 8  is an OH; or 
       (b) a pharmaceutically acceptable salt of said compound; and 
       (c) a pharmaceutically-acceptable carrier. 
     
   
   
       16 . A pharmaceutical composition according to  claim 15  wherein said compound has the formula: 
     
       
         
         
             
             
         
       
     
   
   
       17 . A method of providing nutraceutical benefits to a patient comprising the step of administering to the patient a nutraceutical composition including:
 (a) a compound having the formula:   
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9  and R 10  are independently a substituted or un-substituted C 1 -C 3  alkyl group or H; R 8  is an OH; or 
       (b) a pharmaceutically acceptable salt of said compound; and 
       (c) an acceptable carrier. 
     
   
   
       18 . A method according to  claim 17  wherein said compound has the formula: 
     
       
         
         
             
             
         
       
     
   
   
       19 . A method according to  claim 17  wherein said nutraceutical composition further comprises an immune boosting agent, anti-inflammatory agent, anti-oxidant agent or a mixture thereof. 
   
   
       20 . A nutraceutical composition comprising:
 (a) a compound having the formula:   
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9  and R 10  are independently a substituted or un-substituted C 1 -C 3  alkyl group or H; R 8  is an OH; or 
       (b) a pharmaceutically acceptable salt of said compound; and 
       (c) an acceptable carrier. 
     
   
   
       21 . A nutraceutical composition according to  claim 20  wherein said compound has the formula: 
     
       
         
         
             
             
         
       
     
   
   
       22 . A nutraceutical composition according to  claim 20  further comprising an immune boosting agent, anti-inflammatory agent, anti-oxidant agent, or a mixture thereof.