Methods for treating testicular and ovarian adrenal rest tumors

Abstract

Provided herein are compounds and pharmaceutical compositions for the prevention and treatment of testicular adrenal rest tumors (TART) or ovarian adrenal rest tumors (OART).

What is claimed is: 
     
         1 . A method of treating or preventing testicular adrenal rest tumors (TART) or ovarian adrenal rest tumors (OART), comprising administering to a subject in need thereof a compound of Formula (I), 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         R 1  and R 2  are independently ethyl or n-propyl; 
         R 3  is hydrogen, Cl, Br, methyl, trifluoromethyl, or methoxy; 
         R 4  is hydrogen, Br, R a R b N—, methoxymethyl, n-butyl, acetamido, pyridin-4-yl, morpholin-4-yl, 
       
       
         
           
           
               
               
           
         
       
       and
 R a  and R b  are independently hydrogen, C 1 -C 3 alkyl, H 2 NCH 2 CH 2 —, (CH 3 ) 3 COC(O)NHCH 2 CH 2 —, or CH 3 CH 2 CH 2 NHCH 2 CH 2 —. 
 
     
     
         2 . The method of  claim 1 , wherein the subject has congenital adrenal hyperplasia (CAH). 
     
     
         3 . The method of  claim 1 , wherein the size of the tumors is reduced. 
     
     
         4 . The method of  claim 1 , wherein the number of the tumors is decreased. 
     
     
         5 . The method of  claim 1 , wherein both the size and the number of the tumors are reduced or decreased. 
     
     
         6 . The method of  claim 1 , wherein R 3  is Cl, Br, methyl, or trifluoromethyl. 
     
     
         7 . The method of  claim 1 , wherein R 4  is Br, RaR b N—, pyridin-4-yl, morpholin-4-yl, or 
       
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 1 , wherein R 4  is morpholin-4-yl or 
       
         
           
           
               
               
           
         
       
     
     
         9 . The method of  claim 1 , wherein R 4  is hydrogen, Br, R a R b N— and R a  and R b  are independently C 1 -C 3 alkyl. 
     
     
         10 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         12 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         13 . The method of  claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered at a dose of about 5 mg/day to about 100 mg/day to the subject. 
     
     
         14 . The method of  claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered at a dose of about 10 mg/day to about 400 mg/day to the subject. 
     
     
         15 . The method of  claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered orally. 
     
     
         16 . The method of  claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is formulated as a capsule or tablet. 
     
     
         17 . The method of  claim 1 , further comprising administering to the subject an additional chemotherapeutic agent. 
     
     
         18 . The method of  claim 17 , wherein the additional chemotherapeutic agent is a glucocorticoid, a mineralocorticoid, an ACAT1 inhibitor, or an anti-androgen. 
     
     
         19 . The method of  claim 18 , wherein the glucocorticoid is beclomethasone, betamethasone, budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, or triamcinolone. 
     
     
         20 . A compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         R 1  and R 2  are independently ethyl or n-propyl; 
         R 3  is hydrogen, Cl, Br, methyl, trifluoromethyl, or methoxy; 
         R 4  is hydrogen, Br, R a R b N—, methoxymethyl, n-butyl, acetamido, pyridin-4-yl, 
         morpholin-4-yl, 
       
       
         
           
           
               
               
           
         
         R a  and R b  are independently hydrogen, C 1 -C 3 alkyl, H 2 NCH 2 CH 2 —, 
         (CH 3 ) 3 COC(O)NHCH 2 CH 2 —, or CH 3 CH 2 CH 2 NHCH 2 CH 2 —.