US2016264556A1PendingUtilityA1

Itraconazole analogs and use thereof

Assignee: UNIV JOHNS HOPKINSPriority: Sep 7, 2011Filed: May 23, 2016Published: Sep 15, 2016
Est. expirySep 7, 2031(~5.1 yrs left)· nominal 20-yr term from priority
A61K 31/496A61K 31/506C07D 405/14A61P 35/00
50
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Claims

Abstract

Provided herein are Itraconazole analogs. Also provided herein are methods of inhibition of Hedgehog pathway, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, angiogenesis and treatment of disease with Itraconazole analogs.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A compound of structural Formula (I): 
       
         
           
           
               
               
           
         
         or an optically pure stereoisomer or pharmaceutically acceptable salt thereof, wherein: 
         X and Y are each independently CH, or N; 
         A is CR 6  or N; 
         B is CR 7  or N; 
         W is CR 8  or N; 
         V is CR 9  or N; 
         Z is CR 10  or N; 
         Q is O or CH 2 ; 
         each R 2 , R 3 , R 4 , and R 5  are independently chosen from the group consisting of alkoxy, alkyl, amino, halogen, hydroxy, haloalkyl, perhaloalkyl, perhaloalkoxy, nitro, and cyano; 
         R 6 , R 7 , R 8 , and R 9  are each independently chosen from the group consisting of hydrogen, alkoxy, alkyl, amino, halogen, hydroxy, haloalkyl, perhaloalkyl, perhaloalkoxy, nitro, and cyano; 
         T is —OR 11  or hydrogen; 
         R 11  is hydrogen or alkyl; 
         G is —(CH 2 ) n  or G and R 11  may optionally be joined together to form a dioxolane; 
         R 1  and R 10  are each independently hydrogen or alkyl; 
         n is an integer between 0 and 2; 
         p and t are each independently an integer between 0 and 2; 
         q and m are each independently an integer between 0 and 4; 
         D is chosen from the group consisting of 
       
       
         
           
           
               
               
           
         
         U is O or S; 
         R 12  and R 13  are each independently chosen from the group consisting of hydrogen and alkyl; and 
         R 14  is chosen from the group consisting of hydrogen, alkyl, arylalkyl, alkoxyalkyl, arylalkoxy, alkynylalkyl, alkenylalkyl, cycloalkyl, cyanoalkyl, cycloalkylalkyl, heteroalkyl, heterocycloalkyl, heteroaryl, heteroarylalkyl, and heterocycloalkylalkyl. 
       
     
     
         2 . The compound of  claim 1 , wherein:
 X and Z are N;   Y is CH;   A is CR 6 ;   B is CR 7 ;   W is CR 8 ;   V is CR 9 ;   D is   
       
         
           
           
               
               
           
         
         p, t, and q are each independently 0; 
         m is 2; and 
         R 1 , R 6 , R 7 , R 8 , and R 9  are each independently hydrogen. 
       
     
     
         3 . The compound of  claim 2 , wherein the compound is of structural Formula (II): 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 3 , wherein Q is CH 2 . 
     
     
         5 . The compound of  claim 4 , wherein T is hydrogen. 
     
     
         6 . The compound of  claim 4 , wherein:
 T is OR 11 ; and   R 11  is hydrogen.   
     
     
         7 . The compound of  claim 3 , wherein Q is O. 
     
     
         8 . The compound of  claim 7 , wherein T is hydrogen. 
     
     
         9 . The compound of  claim 7 , wherein:
 T is OR11; and   R11 is hydrogen.   
     
     
         10 . The compound of  claim 2 , wherein the compound is of structural Formula (III): 
       
         
           
           
               
               
           
         
         wherein: 
         R 14  is chosen from the group consisting of hydrogen, alkyl, arylalkyl, alkoxyalkyl, arylalkoxy, alkynylalkyl, alkenylalkyl, cycloalkyl, cyanoalkyl, cycloalkylalkyl, and heterocycloalkylalkyl. 
       
     
     
         11 . The compound of  claim 1 , wherein the compound is of structural Formula (IV): 
       
         
           
           
               
               
           
         
       
     
     
         12 . The compound of  claim 11 , wherein:
 m is 2; and   each R 2  is independently chlorine.   
     
     
         13 . The compound of  claim 12 , wherein R 14  is 
       
         
           
           
               
               
           
         
       
     
     
         14 . The compound of  claim 13 , wherein:
 W is CR8; and   V is CR9.   
     
     
         15 . The compound of  claim 14 , wherein p is 0. 
     
     
         16 . The compound of  claim 15 , wherein:
 each R4 is independently alkyl; and   q is 0, 1, or 2.   
     
     
         17 . The compound of  claim 16 , wherein:
 each R5 is independently halogen; and   t is 0, 1, or 2.   
     
     
         18 . The compound of  claim 17 , wherein A is CR 6 . 
     
     
         19 . The compound of  claim 18 , wherein B is CR 7 . 
     
     
         20 . The compound of  claim 18 , wherein B is N.

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