Prostaglandin endoperoxide H synthase biosynthesis inhibitors

Abstract

The present invention describes pyridazinone compounds of formula I which are cyclooxygenase (COX) inhibitors, and in particular, are selective inhibitors of cyclooxygenase-2 (COX-2). COX-2 is the inducible isoform associated with inflammation, as opposed to the constitutive isoform, cyclooxygenase-1 (COX-1) which is an important “housekeeping” enzyme in many tissues, including the gastrointestinal (GI) tract and the kidneys. The selectivity of these compounds for COX-2 minimizes the unwanted GI and renal side-effects seen with currently marketed non-steroidal anti-inflammatory drugs (NSAIDs).

1 - 55 . (canceled) 
   
   
       56 . A method for treating cancer in a patient in need thereof comprising administering a prostaglandin-inhibiting compound of formula III 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt or ester thereof, wherein
 R is selected from the group consisting of a) alkyl, b) aryl, wherein the aryl is optionally substituted phenyl wherein said substituents are selected from alkyl, halogen, and haloalkyl, c) arylalkyl wherein the aryl of arylalkyl is optionally substituted phenyl wherein said substituents are selected from alkyl, halogen, and haloalkyl, d) haloalkyl, and e) haloalkenyl; 
 R 1  is hydroxyalkoxy; and 
 R 9  is selected from the group consisting of alkyl and amino. 
 
   
   
       57 . A method according to  claim 56  wherein the compound is selected from the group consisting of 2-(4-fluorophenyl)-4-(3-hydroxy-3-methyl-1-butoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone and 2-(3,4-difluorophenyl)-4-(3-hydroxy-3-methyl-1-butoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone.