Compounds act at multiple prostaglandin receptors giving a general anti-inflammatory response

Abstract

The present invention provides a compound, that is a 1-[(2-{[(alkyl or aryl)methyl]oxy}halo or haloalkyl substituted-phenyl)alkyl]-5-hydrocarbyl or substituted hydrocarbyl-1H-pyrazole carboxylic acid or alkylenylcarboxylic acid or a hydrocarbyl or substituted hydrocarbyl sulfonamide of said carboxylic acid or said alkylenylcarboxylic acid, provided however said compound is not a 3-carboxylic acid, a sulfonamide thereof, or a 3-methylenylcarboxylic acid. The compound may be represented by the following formula Wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X, W, X and Y are as defined in the specification. The compounds may be administered to treat DP1, FP, EP1, TP and/or EP4 receptor mediated diseases or conditions.

What is claimed is: 
     
         1 . A compound, that is a 1-[(2-{[(alkyl or aryl)methyl]oxy} halo or haloalkyl substituted-phenyl)alkyl]-5-hydrocarbyl or substituted hydrocarbyl-1H-pyrazole carboxylic acid or alkylenylcarboxylic acid or a hydrocarbyl or substituted hydrocarbyl sulfonamide of said carboxylic acid or said alkylenylcarboxylic acid, provided however said compound is not a 3-carboxylic acid, a sulfonamide thereof, or a 3-methylenylcarboxylic acid. 
     
     
         2 . A compound according to  claim 1 , wherein said 5-hydrocarbyl is 5-methyl. 
     
     
         3 . A compound according to  claim 2 , wherein said halo or haloalkyl substituted-phenylalkyl is halo or haloalkyl substituted-phenyl)methyl. 
     
     
         4 . A compound according to  claim 3 , that is a 1-[(2-{[(alkyl)methyl]oxy} halo or haloalkyl-substituted phenyl)methyl]-5-methyl-1H-pyrazole-3-ethylenylcarboxylic acid, wherein said halo is selected from the group consisting of fluoro, chloro and bromo. 
     
     
         5 . A compound according to  claim 3 , that is a 1-[(2-{[(aryl)methyl]oxy} halo or haloalkyl-substituted phenyl)methyl]-5-methyl-1H-pyrazole-3-carboxylic acid fluoro-substituted alkylsulfonamide or alkylenylcarboxylic acid fluoro-substituted alkylsulfonamide, wherein said halo is selected from the group consisting of fluoro, chloro and bromo. 
     
     
         6 . The compound of  claim 4 , wherein said halo or haloalkyl-substituted phenyl is selected from the group consisting of trifluoromethylphenyl, chlorophenyl and bromophenyl. 
     
     
         7 . The compound of  claim 3 , wherein said halo or haloalkyl-substituted phenyl is selected from the group consisting of trifluoromethylphenyl, chlorophenyl and bromophenyl. 
     
     
         8 . The compound of  claim 1 , wherein said compound is a trifluoromethylsulfonamide and said aryl is chlorophenyl. 
     
     
         9 . The compound of  claim 6 , wherein said alkyl is 3-pentyl. 
     
     
         10 . The compound of  claim 6 , wherein said alkyl is cyclopentyl. 
     
     
         11 . The compound of  claim 6 , wherein W is cyclopentyl. 
     
     
         12 . A method for decreasing the secretion of cytokines from a macrophage comprising administering a compound having the following formula 
       
         
           
           
               
               
           
         
         Wherein R 1  is selected from the group consisting of OR 7 , N(R 7 ) 2 , and N(R 2 )SO 2 R 7  wherein R 7  is selected from the group consisting of H, alkyl and aryl, wherein said alkyl and aryl may be substituted with fluoro; 
         R 2  is selected from the group consisting of H and alkyl; 
         R 3  is selected from the group consisting of H and alkyl; wherein R 2  and R 3 , individually or together, can form a cycloalkyl ring; 
         X is (CH 2 ) n  wherein n is 0 or an integer of from 1 to 3, provided however that when n is 0 or 1, R 1  is not OR 7 . or NR 2 ; 
         R 4  is selected from the group consisting of H, alkyl and fluoroalkyl; 
         R 5  is selected from the group consisting of H, hydroxy, alkyl, aryl, alkoxy, aryloxy, halogen, nitro, amino, cyano and hydroxy, halogen, nitro, amino and cyano-substituted alkyl, aryl, alkoxy or aryloxy; 
         R 6  is selected from the group consisting of H, hydroxy, alkyl, aryl, alkoxy, aryloxy, halogen, nitro, amino, cyano and hydroxy, halogen, nitro, amino and cyano-substituted alkyl, aryl, alkoxy and aryloxy; 
         Z is (CH 2 ) m  wherein m is 0 or an integer of from 1 to 3; 
         Y is selected from the group consisting of O, S, SO, SO 2  and (CH 2 ) p , wherein p is 0 or an integer of from 1 to 3; and 
         W is selected from the group consisting of alkyl and aryl. 
       
     
     
         13 . The method of  claim 12 , wherein said compound is administered to treat DP1, FP, EP1, TP and/or EP4 receptor mediated diseases or conditions. 
     
     
         14 . A method according to  claim 12 , wherein said cytokine is TNFα and said compound is administered for treating diseases resulting from the stimulation of the production of proinflammatory cytokines/chemokines, collagenases, metalloproteinases, and other inflammatory mediators; activation of endothelial cells and neutrophils; promotion T- and B-cell growth, as well as stimulation of bone resorption, the production of local and systemic proinflammatory cytokines/chemokines and serum MMP-3, nitric oxide synthase activity, VEGF release, and angiogenesis in inflamed joints. 
     
     
         15 . A method according to  claim 12 , wherein said macrophage is a human macrophage.