Treprostinil prodrugs

Abstract

Provided are novel prodrugs of treprostinil, as well as methods of making and methods of using these prodrugs.

What is claimed is: 
     
         1 . A compound having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         2 . A pharmaceutical composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         3 . The pharmaceutical composition of  claim 2 , which is a composition formulated for subcutaneous administration. 
     
     
         4 . The pharmaceutical composition of  claim 2 , which is a composition formulated for oral administration. 
     
     
         5 . A method of treating pulmonary hypertension comprising administering to a patient suffering from pulmonary hypertension an effective amount of a compound having the following formula: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 5 , wherein the administration is oral administration. 
     
     
         7 . The method of  claim 5 , wherein the subject is a human being. 
     
     
         8 . The method of  claim 5 , wherein the administration is by an injection. 
     
     
         9 . The method of  claim 8 , wherein the administration is subcutaneous administration. 
     
     
         10 . The method of  claim 9 , wherein said administration is continuous subcutaneous administration. 
     
     
         11 . The method of  claim 9 , wherein said administration results in no or less pain at a site of the injection compared to administering treprostinil. 
     
     
         12 . The method of  claim 9 , wherein the compound converts in whole or in part to treprostinil in vivo following the administration and has reduced affinity for one or more of the IP, DP or EP receptors locally at the site of the subcutaneous injection as compared to treprostinil. 
     
     
         13 . The method of  claim 5 , wherein the patient is a human, wherein said compound has a half-life of less than 120 minutes. 
     
     
         14 . The method of  claim 13 , wherein the compound has a half-life of less than 60 minutes. 
     
     
         15 . The method of  claim 14 , wherein said compound has the half-life in plasma of less than 30 minutes. 
     
     
         16 . The method of  claim 15 , wherein said compound has the half-life in plasma of less than 15 minutes.