Steroid Analogues for Neuroprotection

Abstract

Provided are steroid analogues functionalized with polar substituents at the C3 and/or C20 positions of the steroid ring system that exhibit improved water solubility. Also provided are pharmaceutical compositions comprising the steroid analogues and methods using the novel steroid analogues for the treatment and prevention of neurodegeneration in a patient following injury to the central nervous system.

What is claimed is: 
     
         1 . A method of treating or preventing neurodegeneration following injury to the central nervous system comprising administering to a subject in need thereof an effective amount of a compound of the following formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         R 1 , R 2 , R 5  and R 6  are independently hydrogen, alkyl, halogen, hydroxyl cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, heterocyclic, heteroaryl, amino, thiol, alkoxy, sulfide, nitro, cyano, azide, sulfonyl, acyl, carboxyl, an ester, an amide, carbamate, carbonate, an amino acid residue or a carbohydrate; 
         R 3  is —OR 11 ; 
         R 11  is —C(O)R′, where R′ is alkyl, or the residue of an amino acid;
 and 
 the dotted line indicates the presence of either a single bond or a double bond, wherein valences of a single bond are completed by hydrogens. 
 
       
     
     
         2 . The method of  claim 1 , wherein neurodegeneration following injury to the central nervous system is traumatic brain injury or stroke. 
     
     
         3 . The method of  claim 1 , wherein R 1 , R 2 , R 5  and R 6  are independently hydrogen or alkyl. 
     
     
         4 . The method of  claim 1  wherein the compound is selected from,