Novel anti-inflammatory androstane derivatives

Abstract

Novel anti-inflammatory androstane derivatives There are provided compound of formula (I) wherein R 1 represents C 1-6 alkyl or C 1-6 haloalkyl; R 2 represents C 3-8 cycloalkyl or C 3-8 cycloalkenyl either of which may optionally be substituted by one or more groups selected from oxo, methyl, methylene and halogen; R 3 represents hydrogen, methyl (which may be in either the α or β configuration) or methylene; R 4 and R 5 are the same or different and each represents hydrogen or halogen; and represents a single or a double bond; and solvates thereof, processes for preparing them and their use in therapy.

1 . A method for the treatment of a human or animal subject having an inflammatory and/or allergic condition, which method comprises administering to the human or animal subject an effective amount of a pharmaceutical composition comprising a compound 6α,9α-Difluoro-11β-hydroxy-16α-methyl-17α-(1-methycyclopropylcarbonyl)oxy-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester, in admixture with one or more physiologically acceptable diluents or carriers, wherein said effective amount is from 20 to 2000 micrograms of said compound.  
   
   
       2 . The method of  claim 1 , wherein said administration occurs from 1 to 8 times per day.  
   
   
       3 . The method of  claim 2 , wherein said administration occurs once per day.  
   
   
       4 . The method of  claim 1 , wherein the inflammatory and/or allergic condition is rhinitis.  
   
   
       5 . The method of  claim 1 , wherein said effective amount is from 20-500 micrograms of said compound.  
   
   
       6 . The method of  claim 1 , wherein said pharmaceutical composition is an aqueous formulation, and said administration is made via aerosolization and is topically delivered to the nasal cavity.  
   
   
       7 . The method of  claim 6 , wherein said composition comprises a buffering agent and/or a tonicity modifying agent.  
   
   
       8 . The method of  claim 1 , wherein said composition further comprises an antihistamine as a further pharmaceutically active compound for the treatment of said condition.  
   
   
       9 . A method for the treatment of a human or animal subject having an inflammatory and/or allergic condition, which method comprises: 
 administering to the nasal cavity of the human or animal subject, an aqueous aerosol pharmaceutical composition comprising an effective amount of a compound 6α,9α-Difluoro-11β-hydroxy-16α-methyl-17α-(1-methycyclopropylcarbonyl)oxy-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl or a solvate thereof, wherein said effective amount is from 20-2000 micrograms of said compound.    
   
   
       10 . The method of  claim 9 , wherein said effective amount of said aqueous aerosol pharmaceutical composition is delivered from one to four times per day.  
   
   
       11 . The method of  claim 10 , wherein said aqueous aerosol pharmaceutical composition is delivered once per day.