US2012258936A1PendingUtilityA1

Inositol hexakisphosphate analogs and uses thereof

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Assignee: SAVIDGE TOR CPriority: Apr 6, 2011Filed: Apr 6, 2012Published: Oct 11, 2012
Est. expiryApr 6, 2031(~4.7 yrs left)· nominal 20-yr term from priority
C07F 9/117C07F 9/06A61P 31/04C07F 9/177C07F 9/70
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Claims

Abstract

Provided herein are analog and derivative compounds of inositol hexakisphosphate effective to treat a Clostridium difficile infection and to neutralize the bacterial toxins produced by the same. In addition, methods of treating the C. difficile infection and for neutralizing its toxins with the compounds are provided.

Claims

exact text as granted — not AI-modified
1 . An inositol hexakisphosphate analog having a chemical structure of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6  independently are —PO(OH) 2 , —PS(OH) 2 , —PSe(OH) 2 , or —AsO 3 ; at least one of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6  is —PS(OH) 2 , —PSe(OH) 2 , or —AsO 3 ; and R 1  and R 3  are not both —PS(OH) 2  or —PSe(OH) 2  when R 2 , R 4 , R 5 , and R 6  are —PO(OH) 2 . 
     
     
         2 . The analog of  claim 1 , wherein R 1  and one of R 2 , R 4 , R 5 , or R 6  are —PS(OH) 2 . 
     
     
         3 . The analog of  claim 1 , wherein R 1 , R 2 , and one of R 3 , R 4 , R 5 , or R 6  are —PS(OH) 2 . 
     
     
         4 . The analog of  claim 1 , wherein R 1 , R 4 , and one of R 2 , R 3 , R 5 , or R 6  are —PS(OH) 2 . 
     
     
         5 . The analog of  claim 1 , wherein R 1 , R 5 , and one of R 2 , R 3 , R 4 , or R 6  is —PS(OH) 2 . 
     
     
         6 . The analog of  claim 1 , wherein R 1 , R 6  and one of R 2 , R 3 , R 4 , or R 5  are —PS(OH) 2 . 
     
     
         7 . The analog of  claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6  are —PS(OH) 2 . 
     
     
         8 . The analog of  claim 7 , wherein the inositol analog is a myo-inositol analog. 
     
     
         9 . The analog of  claim 1 , wherein R 1  and one of R 2 , R 4 , R 5 , or R 6  are —PSe(OH) 2 . 
     
     
         10 . The analog of  claim 1 , wherein R 1 , R 2 , and one of R 3 , R 4 , R 5 , or R 6  are —PSe(OH) 2 . 
     
     
         11 . The analog of  claim 1 , wherein R 1 , R 4 , and one of R 2 , R 3 , R 5 , or R 6  are —PSe(OH) 2 . 
     
     
         12 . The analog of  claim 1 , wherein R 1 , R 5 , and one of R 2 , R 3 , R 4 , or R 6  is —PSe(OH) 2 . 
     
     
         13 . The analog of  claim 1 , wherein R 1 , R 6  and one of R 2 , R 3 , R 4 , or R 5  are —PSe(OH) 2 . 
     
     
         14 . The analog of  claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6  are —PSe(OH) 2 . 
     
     
         15 . The analog of  claim 14 , wherein the inositol analog is a myo-inositol analog. 
     
     
         16 . The analog of  claim 1 , wherein nitric oxide (NO) is bound to at least one of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 . 
     
     
         17 . The analog of  claim 16 , wherein NO is bound to —PS(OH) 2 , or —PSe(OH) 2 . 
     
     
         18 . The analog of  claim 16 , wherein NO is covalently bound. 
     
     
         19 . The analog of  claim 16 , wherein NO is ionically bound. 
     
     
         20 . A pharmaceutical composition comprising the analog of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         21 . A method for neutralizing a  Clostridium difficile  bacterial toxin, comprising contacting the  C. difficile  bacterial toxin with the analog of  claim 1 . 
     
     
         22 . The method of  claim 21 , wherein the  Clostridium difficile  bacterial toxin is TcdA, TcdB, or TcdA and TcdB. 
     
     
         23 . A method for treating a subject having a  Clostridium difficile  infection, comprising: administering to the subject an effective dose of the analog of  claim 1 . 
     
     
         24 . The method of  claim 23 , wherein the analog is administered orally. 
     
     
         25 . An inositol hexakisphosphate analog having a chemical structure of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6  independently are —PO(OH) 2 , or —PO(OH) 2 NO, and at least one of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6  is —PO(OH) 2 NO.

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