Substituted 1,3-Dioxanes and There 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 . A compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3 , and R 4  can be independently selected to be hydrogen, halo, haloalkyl, cyano, nitro, hydroxyl, alkyl, alkenyl, aryl, alkoxyl, aryloxyl, aralkoxyl, alkylcarbamido, arylcarbamido, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonylamido, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl or heteroaryl. 
       
     
     
         2 . A compound of formula (II) 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , and R 4  can be independently selected to be hydrogen, halo, haloalkyl, cyano, nitro, hydroxyl, alkyl, alkenyl, aryl, alkoxyl, aryloxyl, aralkoxyl, alkylcarbamido, arylcarbamido, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonylamido, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl or heteroaryl; and Ar is phenyl, phenol, aniline, o-methoxyphenyl, m-methoxyphenyl, or p-methoxyphenyl. 
       
     
     
         3 - 5 . (canceled) 
     
     
         6 . A compound of formula (IV): 
       
         
           
           
               
               
           
         
         wherein R 1  is hydrogen, halogen, cyano, hydroxyl, or alkyl; 
         R 2  is hydrogen, alkyl, alkenyl, aryl, heteroaryl, or 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 0, 1, 2, 3, 4, or 5. 
       
     
     
         7 - 19 . (canceled) 
     
     
         20 . A method for treating or preventing a disorder associated with a thromboxane A2 or peroxisome proliferator-activated receptors, the method comprising: administering to a subject an effective amount of a compound of  claim 1  or acceptable salts, N-oxides, hydrates, or solvates thereof; and a pharmaceutically-acceptable carrier or diluent. 
     
     
         21 . The method of  claim 20 , wherein the disorder is cancer. 
     
     
         22 - 28 . (canceled) 
     
     
         29 . The method according to  claim 20 , wherein said disorder is selected from the group consisting of myocardial infarction, thrombosis, thrombotic disorders, pulmonary hypertension, atherosclerosis, diabetic nephropathy, retinopathy, peripheral arterial disease, lower limb circulation, pulmonary embolism, thrombus formation, stent-triggered thrombus formation, stent-triggered hyperplasia hyperplasia, septic shock, preeclampsia, asthma, allergic rhinitis, tumour angiogenesis and metastasis. 
     
     
         30 - 34 . (canceled) 
     
     
         35 . A pharmaceutical composition comprising the compound according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         36 - 39 . (canceled)