Soluble honokiol derivatives

Abstract

The invention provides a soluble honokiol detivative (such as a water soluble honokiol derivative) and its application in antagonizing glycoprotein VI receptor and providing antioxidant and neuroprotective effects.

What is claimed is: 
     
         1 . A compound having the following Formula (I), 
       
         
           
           
               
               
           
         
         wherein 
         X is (CH 2 ) 1-6 ; 
         R 1  is phosphate or carbonate; 
         R 2  and R 3  are each independently C 2-6 alkenyl, C 1-10 alkyl, —O—C 1-10 alkyl or —NH—C 1-10 alkyl, wherein the alkyl or alkenyl is unsubstituted or substituted; and 
         R 4  and R 5  are each independently one to three H, halogen, —OH, —NH 2 , NO 2 , C 1-10 alkyl, C 2-6  alkenyl, —O—C 1-10 alkyl or —NH—C 1-10 alkyl; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The compound of  claim 1 , wherein R 1  is phosphate; R 2  and R 3  are each independently C 2-6 alkenyl; and R 4  and R 5  are each independently H; or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The compound of  claim 1 , wherein R 2  and R 3  are each independently ethenyl; or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The compound of  claim 1 , wherein the pharmaceutically acceptable salt is a sodium salt. 
     
     
         5 . The compound of  claim 1 , which is 3′,5-diallyl-[1,1′-biphenyl]-2,4′-diyl bis(phosphate), or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The compound of  claim 1 , which is sodium 3′,5-diallyl-[1,1′-biphenyl]-2,4′-diyl bis(phosphate). 
     
     
         7 . A pharmaceutical composition, which comprises a therapeutically effective amount of a compound of  claim 1  and optionally one or more pharmaceutically acceptable carriers and/or excipients. 
     
     
         8 . The pharmaceutical composition of  claim 7 , which is in a dosage form. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the dosage form is an injection dosage form. 
     
     
         10 . A method of antagonizing glycoprotein VI receptor, comprising administration of a therapeutically effective amount of a compound of  claim 1  to a subject. 
     
     
         11 . The method of  claim 10 , wherein the platelet aggregation can be inhibited. 
     
     
         12 . A method of providing antioxidant and neuroprotective effects in a subject, comprising administering a therapeutically effective amount of a compound of  claim 1  to a subject. 
     
     
         14 . The method of  claim 12 , wherein the method does not cause hemorrhage. 
     
     
         15 . The method of  claim 12 , wherein the method reduces edema. 
     
     
         16 . The method of  claim 12 , wherein the compound has a prolonged half-life compared to honokiol. 
     
     
         17 . The method of  claim 12 , wherein the compound converts to honokiol in plasma. 
     
     
         18 . The method of  claim 12 , wherein the neuroprotective effect diminishes brain damage in the subject. 
     
     
         19 . The method of  claim 18 , wherein the brain damage is ischemic stroke. 
     
     
         20 . The method of  claim 12 , wherein the administration is parenteral administration. 
     
     
         21 . The method of  claim 20 , wherein the parenteral administration is intravenous, intramuscular or intracranial administration.