US2011301183A1PendingUtilityA1

Chemical synthesis of a highly potent epothilone

Individually held — no corporate assignee on recordPriority: Nov 22, 2005Filed: Aug 19, 2011Published: Dec 8, 2011
Est. expiryNov 22, 2025(expired)· nominal 20-yr term from priority
C07D 493/04C07D 519/00A61P 35/00C07D 417/06C07D 405/06
40
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Claims

Abstract

A highly active synthetic epothilone compound whose activity exceeds that of either epothilone EpoA or EpoB when assayed as a cytotoxic agent against a cancer cell line is disclosed as is a pharmaceutical composition containing the synthetic epothilone.

Claims

exact text as granted — not AI-modified
1 . A compound that corresponds in structure to Formula A-1, A-2, A-3 or A-4 
       
         
           
           
               
               
           
         
         wherein R A  is an aromatic ring having the structure 
       
       
         
           
           
               
               
           
         
         wherein the depicted five-membered ring is aromatic and contains at least two ring atoms that are other than carbon, 
         each of X 1 , X 2  and X 3  is independently S, NR 1 , N, CH, or CR 2 , 
         R 1  is C 1 -C 8 -hydrocarbyl or methylene-C 1 -C 8 -hydrocarbylether, and 
         R 2  is selected from the group consisting of C 1 -C 8 -hydrocarbyl, O—C 1 -C 8 -hydrocarbyl, halo, S—C 1 -C 8 -hydrocarbyl, methylenethio-C 1 -C 8 -hydrocarbyl and methylenethio-C 1 -C 8 -acyl, and 
         X 2  and X 3  together form a six-membered aromatic ring fused to the depicted five-membered aromatic ring. 
       
     
     
         2 - 5 . (canceled) 
     
     
         6 . The compound according to  claim 1  wherein X 1  is S. 
     
     
         7 - 17 . (canceled) 
     
     
         18 . The compound according to  claim 1  wherein R A  is 
       
         
           
           
               
               
           
         
       
     
     
         19 . The compound according to  claim 1  that corresponds in structure to Formula A-1. 
     
     
         20 . A compound that corresponds in structure to Formula B-1, B-2, B-3 or B-4 
       
         
           
           
               
               
           
         
         wherein R B  is an aromatic ring having the structure 
       
       
         
           
           
               
               
           
         
         wherein
 R 1  is selected from the group consisting of C 1 -C 8 -hydrocarbyl and methylene-C 1 -C 8 -hydrocarbylether, and 
 R 2  is selected from the group consisting of C 1 -C 8 -hydrocarbyl, O—C 1 -C 8 -hydrocarbyl, halo, S—C 1 -C 8 -hydrocarbyl, methylenethio-C 1 -C 8 -hydrocarbyl and methylenethio-C 1 -C 8 -acyl. 
 
       
     
     
         21 . The compound according to  claim 20  wherein R 1  is C 1 -C 8 -hydrocarbyl. 
     
     
         22 . The compound according to  claim 20  wherein R 2  is S—C 1 -C 8 -hydrocarbyl. 
     
     
         23 . The compound according to  claim 20  wherein R 1  is O—C 1 -C 8 -hydrocarbyl. 
     
     
         24 . The compound according to  claim 20  wherein R 1  is halo. 
     
     
         25 . A compound that corresponds in structure to Formula C-1, C-2, C-3 or C-4 
       
         
           
           
               
               
           
         
         wherein R C  is an aromatic ring having a structure selected from the group consisting of 
       
       
         
           
           
               
               
           
         
       
     
     
         26 . A compound that corresponds in structure to the formula 
       
         
           
           
               
               
           
         
       
     
     
         27 - 28 . (canceled) 
     
     
         29 . A composition containing a pharmaceutically effective amount of a compound of  claim 1  dissolved or dispersed in a pharmaceutically acceptable diluent. 
     
     
         30 . The composition according to  claim 29  wherein R A  is 
       
         
           
           
               
               
           
         
       
     
     
         31 . A pharmaceutical composition comprising a compound according to  claim 19  present in an effective amount dissolved or dispersed in a pharmaceutically acceptable diluent. 
     
     
         32 . The composition according to  claim 31  wherein R B  is

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