Corticotropin releasing factor receptor antagonists

Abstract

The present invention provides novel pharmaceutical compositions comprising -(4-Chloro-2-(morpholin-4-yl)thiazol-5-yl)-7-(1-ethylpropyl)-2,5-dimethylpyrazolo(1,5-a)pyrimidine and methods of using the same for the treatment of Congenital adrenal hyperplasia (CAH).

1 .- 180 . (canceled) 
     
     
         181 . A method of treating congenital adrenal hyperplasia (CAH), hyperandrogenic symptoms, menstrual irregularity, ovulatory dysfunction or infertility in a subject, comprising:
 administering Compound 1:   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or solvate thereof, at a dose between about 50 mg/day and about 800 mg/day. 
       
     
     
         182 . The method of  claim 181 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose between about 50 mg/day and about 200 mg/day. 
     
     
         183 . The method of  claim 181 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose of about 200 mg/day. 
     
     
         184 . The method of  claim 181 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose of about 100 mg/day. 
     
     
         185 . The method of  claim 181 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose of about 75 mg/day. 
     
     
         186 . The method of  claim 181 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose of about 50 mg/day. 
     
     
         187 . The method of  claim 181 , the pharmaceutical composition is administered once a day. 
     
     
         188 . The method of  claim 181 , further comprising administering a glucocorticoid. 
     
     
         189 . The method of  claim 188 , wherein the amount of glucocorticoid is reduced compared to a previously administered dose of the glucocorticoid. 
     
     
         190 . The method of  claim 189 , wherein the reduced amount of glucocorticoid is a reduced daily dose of the glucocorticoid and the previously administered dose of the glucocorticoid is a previously administered daily dose of the glucocorticoid. 
     
     
         191 . The method of  claim 189 , wherein the amount of glucocorticoid is reduced from a supraphysiologic amount to a physiologic amount. 
     
     
         192 . The method of  claim 189 , wherein the amount of glucocorticoid is reduced by about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, or about 60%. 
     
     
         193 . The method of  claim 192 , wherein symptoms associated with high-dose glucocorticoid therapy are reduced, wherein the symptoms associated with high-dose glucocorticoid therapy are obesity, insulin resistance, metabolic abnormalities, hypertension, cardiovascular diseases, or osteoporosis. 
     
     
         194 . The method of  claim 188 , wherein the glucocorticoid is beclomethasone, betamethasone, budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, or triamcinolone. 
     
     
         195 . The method of  claim 194 , wherein the glucocorticoid is hydrocortisone. 
     
     
         196 . The method of  claim 195 , wherein the hydrocortisone is administered at a dose less than about 10 mg/day. 
     
     
         197 . The method of  claim 195 , wherein the hydrocortisone is administered at a dose less than about 5 mg/day. 
     
     
         198 . The method of  claim 188 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered concurrently. 
     
     
         199 . The method of  claim 188 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially. 
     
     
         200 . The method of  claim 199 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially within 24 hours. 
     
     
         201 . The method of  claim 199 , wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially within 2 hours.