1,3-Dioxanes and Their Uses

Abstract

The present invention relates to compounds containing 1,3-dioxane moiety, pharmaceutical compositions thereof, and the use of the compounds and compositions for the modulation of thromboxane A2 or a peroxisome proliferator-activated receptor. The compounds, analogs, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions can be used in the treatment and prevention of cancer.

1 - 5 . (canceled) 
     
     
         6 . A compound of formula (IV): 
       
         
           
           
               
               
           
         
         wherein R 1  is hydrogen; 
         R 2  is a C 3-30  cyclic or heterocyclic ring optionally substituted with one or more substituent; 
         X is CH, or N; 
         R 5  is H, OH, alkoxy, alkyl, or halogen; and 
         n is 1 or 2. 
       
     
     
         7 - 9 . (canceled) 
     
     
         10 . The compound of  claim 6 , wherein R 2  is a C 3-30  cyclic or heterocyclic ring optionally substituted with one or more of hydroxyl, halogen, nitro, aryl, alkoxy or alkyl. 
     
     
         11 . The compound of  claim 6 , wherein R 2  is acenaphthene, benzothiophene, chromanone, indole, julolidine, naphthalene, or quinolone, each of which is optionally substituted with one or more of hydroxyl, halogen, nitro, aryl, alkoxy or alkyl. 
     
     
         12 . (canceled) 
     
     
         13 . The compound of  claim 6 , wherein X is N. 
     
     
         14 . The compound of  claim 6 , wherein X is CH. 
     
     
         15 . The compound of  claim 14 , wherein X is NR 8 , where R 8  is H, methyl, or phenyl. 
     
     
         16 . (canceled) 
     
     
         17 . The compound of  claim 6 , wherein R 2  is a group of the formula: 
       
         
           
           
               
               
           
         
         each of which is optionally substituted with one or more of hydroxyl, halogen, nitro, aryl, alkoxy or alkyl. 
       
     
     
         18 - 20 . (canceled) 
     
     
         21 . A method of treating cancer comprising administration of a compound according to  claim 6  to a subject in need of such treatment. 
     
     
         22 . The method of  claim 21 , wherein the subject is a domestic animal. 
     
     
         23 . The method of  claim 21 , wherein the subject is a human. 
     
     
         24 - 39 . (canceled) 
     
     
         40 . A method of treating tumor angiogenesis or metastasis in a cancer patient comprising administration of a compound according to  claim 6  to the patient. 
     
     
         41 . A compound according to  claim 6 , wherein X is CH, and R 2  is a group of the formula: 
       
         
           
           
               
               
           
         
         where R 2a  and R 2b  are independently hydrogen, hydroxyl, halogen, nitro, aryl, alkoxy or alkyl. 
       
     
     
         42 . A compound according to  claim 6 , which is
 (Z)-6-(2-(6-Chloro-4-oxo-4H-chromen-3-yl)-4-(2-hydroxy phenyl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(2-(5-Chloro-1H-indol-3-yl)-4-(2-hydroxy phenyl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(2-(1,2-Dihydro acenaphthylen-5-yl)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-((2R,4S,5R)-2-(8-hydroxy-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolin-9-yl)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(2-(6,8-Dibromo-4-oxo-4H-chromen-3-yl)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(2-(4,6-Dichloro-2H-chromen-3-yl)-4-(2-hydroxy phenyl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(2-(6,8-Dichloro-4-oxo-4H-chromen-3-yl)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(4-(2-Hydroxy phenyl)-2-(6-nitro-4-oxo-4H-chromen-3-yl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(2-(6-Fluoro-4-oxo-4H-chromen-3-yl)-4-(2-hydroxy phenyl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(2-(2-Chloro-6-methyl quinolin-3-yl)-4-(2-hydroxy phenyl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(2-(3-Benzo[b]thiophen-2-yl)-4-(2-hydroxy phenyl-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-2-((3aR,4R,5R,6aS)-5-(Benzyloxy)-2-oxo-hexa hydro-2H-cyclopenta[b]furan-4-yl)-4-(2-hydroxy phenyl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(2-(2-(4-Fluoro phenyl)-1H-indol-3-yl)-4-(2-hydroxy phenyl)-1,3-dioxan-5-yl)-hex-4-enoic acid;   (Z)-6-(4-(2-Hydroxy phenyl)-2-(1-methyl-1H-indol-3-yl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(2-(6-Chloro-4-oxo-4H-chromen-3-yl)-4-(pyridine-3-yl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (Z)-6-(2-(1H)-Benzo[d][1,2,3]triazol-1-yl)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl)hex-4-enoic acid;   (E)-3-(6-Chloro-4-oxo-4H-chromen-3-yl)-4-(2-hydroxy phenyl)-1,3-dioxan-5-yl)acrylic acid; or   a pharmaceutically acceptable salt thereof.   
     
     
         43 . A compound according to  claim 6 , which is 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.