Compounds and methods for treating aberrant adrenocortical cell disorders

Abstract

Methods and compositions are provided for treatment of disorders associated with aberrant adrenal cortex cell behavior, including (but not limited to) treatment of adrenocortical carcinoma (ACC), Cushing's syndrome and/or pituitary ACTH excess (Cushing's Disease). Such methods involve administration of an effective amount N-(2,6-bis(1-methylethyl)phenyl)-N′-((1-(4-(dimethylamino)phenyl)cyclopentyl)-methyl)urea hydrochloride to the patient.

1 . (canceled) 
     
     
         2 . A method for treating benign adenoma in a patient comprising administering a therapeutically effective amount of N-(2,6-bis(1-methylethyl)phenyl)-N′-((1-(4-(dimethylamino)phenyl)cyclopentyl)-methyl)urea hydrochloride to the patient. 
     
     
         3 .- 11 . (canceled) 
     
     
         12 . The method of  claim 2 , further comprising administering a second therapeutic agent. 
     
     
         13 . The method of  claim 12 , wherein the second therapeutic agent is a chemotherapeutic agent. 
     
     
         14 . The method of  claim 12 , wherein the second therapeutic agent is mitotane. 
     
     
         15 . A method of inhibiting aberrant adrenal hormone production in a patient comprising administering an effective amount of N-(2,6-bis(1-methylethyl)phenyl)-N′-((1-(4-(dimethylamino)phenyl)cyclopentyl)-methyl)urea hydrochloride to the patient to inhibit hormone production. 
     
     
         16 . The method of  claim 15 , further comprising administering a second therapeutic agent. 
     
     
         17 . The method of  claim 15  or  16 , wherein the hormone is a mineralocorticoid, a glucocorticoid, or an androgen 
     
     
         18 . The method of  claim 17 , wherein the mineralocorticoid is aldosterone. 
     
     
         19 . The method of  claim 17 , wherein the androgen is androstenedione, dehydroepiandrosterone, or adrenosterone. 
     
     
         20 . The method of  claim 17 , wherein the glucocorticoid is cortisol. 
     
     
         21 . The method of  claim 2 , wherein the patient suffers from a condition selected from the group consisting of:
 Cushing's syndrome;   Excess cortisol production;   ACTH excess that results in adrenal Cortisol excess;   Pituitary ACTH excess (Pituitary Cushing's Disease);   Ectopic ACTH syndrome;   Primary Adrenal Cortisol Excess;   ACTH independent macronodular hyperplasia (always bilateral); and   congenital adrenal hyperplasia.   
     
     
         22 . The method of  claim 21 , wherein the congenital adrenal hyperplasia is 11 hydroxylase deficiency, 21-hydroxylase deficiency, hyperaldosteronism (Conn syndrome), or bilateral adrenal hyperplasia. 
     
     
         23 . The method of  claim 2 , wherein administering is oral administration. 
     
     
         24 . The method of  claim 2 , wherein N-(2,6-bis(1-methylethyl)phenyl)-N′-((1-(4-(dimethylamino)phenyl)cyclopentyl)-methyl)urea hydrochloride is administered one, two, three or four times daily. 
     
     
         25 . The method of  claim 12 , wherein the second therapeutic agent is selected from the group consisting of:
 Mifepristone;   a chemotherapeutic agent;   Metformin;   Everolimus;   a targeting agent;   an adrenolysis agent; and   an IGF1R antagonist.   
     
     
         26 . A composition comprising N-(2,6-bis(1-methylethyl)phenyl)-N′-((1-(4-(dimethylamino)phenyl)cyclopentyl)-methyl)urea hydrochloride and a second therapeutic agent in a unit dose. 
     
     
         27 . The composition of  claim 26 , wherein the second therapeutic agent is a chemotherapeutic agent. 
     
     
         28 . The composition of  claim 26 , wherein the second therapeutic agent is selected from the group consisting of:
 Mifepristone;   a chemotherapeutic agent;   Metformin;   Everolimus;   a targeting agent;   an adrenolysis agent; and   an IGF1R antagonist.   
     
     
         29 . The method of  claim 15 , wherein administering is oral administration. 
     
     
         30 . The method of  claim 15 , wherein N-(2,6-bis(1-methylethyl)phenyl)-N′-((1-(4-(dimethylamino)phenyl)cyclopentyl)-methyl)urea hydrochloride is administered one, two, three or four times daily.