Fluoro substituted cycloalkanoindoles, compositions containing such compounds and methods of treatment

Abstract

Fluoro substituted cycloalkanoindole derivatives are antagonists of prostaglandins, and as such are useful for the treatment of prostaglandin mediated diseases.

1 - 29 . (canceled) 
     
     
         30 . A method for the treatment of prostaglandin D2 mediated diseases which comprises administering, orally, by inhalation spray, topically, parenterally or rectally in dosage unit formulations containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants and vehicles, to a patient in need of such treatment, a pharmaceutical composition containing a therapeutically effective amount of a compound of Formula I 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein
 n is 0 or 1; m is 1, 2 or 3; R 1  is H, C 1 -C 3  alkyl, halogenated C 1 -C 3  alkyl or cyclopropyl; 
 R 2  is 4-chlorophenyl or 2,4,6-trichlorophenyl. 
 
     
     
         31 . The method of  claim 30 , wherein the pharmaceutical composition may be administered as one or more tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. 
     
     
         32 . The method of  claim 31 , wherein the pharmaceutical composition is a tablet, which contains a compound of Formula I 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein
 n is 0 or 1; m is 1, 2 or 3; R 1  is H, C 1 -C 3  alkyl, halogenated C 1 -C 3  alkyl or cyclopropyl; 
 R 2  is 4-chlorophenyl or 2,4,6-trichlorophenyl; 
 in admixture with non-toxic pharmaceutically acceptable excipients which are suitable for the manufacture of tablets. 
 
     
     
         33 . The method of  claim 31 , wherein the pharmaceutical composition is administered orally as one or more hard gelatin capsules or soft gelatin capsules. 
     
     
         34 . The method of  claim 33 , wherein a hard gelatin capsule is administered, wherein the compound of Formula I is mixed with an inert solid diluent selected from calcium carbonate, calcium phosphate or kaolin. 
     
     
         35 . The method of  claim 33 , wherein a soft gelatin capsule is administered, wherein the compound of Formula I is mixed with 1) water-miscible solvents, selected from propylene glycol, PEGs and ethanol, or 2) an oil medium, selected from peanut oil, liquid paraffin, or olive oil. 
     
     
         36 . The method of  claim 31 , wherein the pharmaceutical composition is administered as an aqueous suspension which contains a compound of Formula I in admixture with excipients suitable for the manufacture of aqueous suspensions. 
     
     
         37 . The method of  claim 36 , wherein the aqueous suspension may optionally contain one or more preservatives, selected from ethyl, or n-propyl, p-hydroxybenzoate, one or more colouring agents, one or more flavouring agents, and one or more sweetening agents, selected from as sucrose, saccharin or aspartame 
     
     
         38 . The method of  claim 31 , wherein the pharmaceutical composition is administered as an oily suspensions. 
     
     
         39 . The method of  claim 38 , wherein the oily suspension is formulated by suspending the compound of Formula I in a vegetable oil, selected from arachis oil, olive oil, sesame oil or coconut oil, or in mineral oil selected from liquid paraffin. 
     
     
         40 . The method of  claim 31 , wherein the pharmaceutical composition is administered as a syrup or elixir. 
     
     
         41 . The method of  claim 40 , wherein the syrup or elixir is formulated with sweetening agents, selected from glycerol, propylene glycol, sorbitol or sucrose. 
     
     
         42 . The method of  30 , wherein the pharmaceutical composition is administered topically as a cream, ointment, gel, solution or suspension. 
     
     
         43 . The method of  claim 42 , wherein the pharmaceutical composition is administered as a topical formulation which contains a pharmaceutical carrier, cosolvent, emulsifier, penetration enhancer, preservative system, or emollient.