P
USRE47741EActiveUtilityPatentIndex 62

Antibacterial aminoglycoside analogs

Assignee: ACHAOGEN INCPriority: May 15, 2009Filed: Jun 14, 2018Granted: Nov 26, 2019
Est. expiryMay 15, 2029(~2.9 yrs left)· nominal 20-yr term from priority
Inventors:DOZZO PAOLAGOLDBLUM ADAM AARONAGGEN JAMES BRADLEYLINSELL MARTIN SHERINGHAM
A61P 31/04C07H 15/236
62
PatentIndex Score
1
Cited by
357
References
22
Claims

Abstract

Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q 1 , Q 2 , Q 3 , R 11 and R 12 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. A compound having the following structure (I): 
       
         
           
           
               
               
           
         
       
       or a stereoisomer or pharmaceutically acceptable salt thereof,
 wherein:
 Q 1  is alkyl optionally substituted with hydroxyl or amino, 
 
 
       
         
           
           
               
               
           
         
         
           Q 2  is hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —C(═NH)NR 7 R 8 , 
         
       
       
         
           
           
               
               
           
         
         
           Q 3  is hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —C(═NH)NR 7 R 8 , 
         
       
       
         
           
           
               
               
           
         
         
           each R 4 , R 5 , R 7 , R 8  and R 11  is, independently, hydrogen or C 1 -C 6  alkyl optionally substituted with one or more halogen, hydroxyl or amino; 
           each R 6  is, independently, hydrogen, halogen, hydroxyl, amino or C 1 -C 6  alkyl; 
           or R 4  and R 5  together with the atoms to which they are attached can form a heterocyclic ring having from 4 to 6 ring atoms, or R 5  and one R 6  together with the atoms to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms, or R 4  and one R 6  together with the atoms to which they are attached can form a carbocyclic ring having from 3 to 6 ring atoms, or R 7  and R 8  together with the atom to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms; 
           each R 9  and R 12  is, independently, hydrogen, hydroxyl, amino or C 1 -C 6  alkyl optionally substituted with one or more halogen, hydroxyl or amino; 
           each R 10  is, independently, hydrogen, halogen, hydroxyl, amino or C 1 -C 6  alkyl; 
           or R 9  and one R 10  together with the atoms to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms; and 
           each n is, independently, an integer from 0 to 4, and 
         
         wherein (i) at least one of Q 2  and Q 3  is other than hydrogen, and (ii) Q 1  is not ethyl or —C(═O)CH 3 . 
       
     
     
       2. A compound of  claim 1  wherein Q 2  is other than hydrogen. 
     
     
       3. A compound of  claim 2  wherein Q 3  is hydrogen. 
     
     
       4. A compound of  claim 2  wherein Q 2  is optionally substituted alkyl. 
     
     
       5. A compound of  claim 4  wherein Q 2  is substituted with hydroxyl or amino. 
     
     
       6. A compound of  claim 1  wherein R 11  is hydrogen. 
     
     
       7. A compound of  claim 1  wherein each R 12  is methyl. 
     
     
       8. A pharmaceutical composition comprising a compound of  claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
       9. A method of treating a bacterial infection in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound of  claim 1  or a composition of  claim 8 . 
     
     
       10. A compound having the following structure (I): 
       
         
           
           
               
               
           
         
       
       or a stereoisomer or pharmaceutically acceptable salt thereof,
 wherein:
 Q 1  is 
 
 
       
         
           
           
               
               
           
         
         
           Q 2  is hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —C(═NH)NR 7 R 8 , 
         
       
       
         
           
           
               
               
           
         
         
           Q 3  is hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —C(═NH)NR 7 R 8 , 
         
       
       
         
           
           
               
               
           
         
         
           each R 4 , R 5 , R 7 , R 8  and R 11  is, independently, hydrogen or C 1 -C 6  alkyl optionally substituted with one or more halogen, hydroxyl or amino; 
           each R 6  is, independently, hydrogen, halogen, hydroxyl, amino or C 1 -C 6  alkyl; 
           or R 4  and R 5  together with the atoms to which they are attached can form a heterocyclic ring having from 4 to 6 ring atoms, or R 5  and one R 6  together with the atoms to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms, or R 4  and one R 6  together with the atoms to which they are attached can form a carbocyclic ring having from 3 to 6 ring atoms, or R 7  and R 8  together with the atom to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms; 
           each R 9  and R 12  is, independently, hydrogen, hydroxyl, amino or C 1 -C 6  alkyl optionally substituted with one or more halogen, hydroxyl or amino; 
           each R 10  is, independently, hydrogen, halogen, hydroxyl, amino or C 1 -C 6  alkyl; 
           or R 9  and one R 10  together with the atoms to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms; and 
           each n is, independently, an integer from 0 to 4, and 
           wherein (i) at least one of Q 2  and Q 3  is other than hydrogen, and (ii) for Q 1 , R 5  and one R 6  together with the atoms to which they are attached form a heterocyclic ring having 3 ring atoms, or R 4  and one R 6  together with the atoms to which they are attached form a carbocyclic ring having 3 ring atoms, or R 9  and one R 10  together with the atoms to which they are attached form a heterocyclic ring having 3 ring atoms. 
         
       
     
     
       11. A compound of  claim 10  wherein Q 2  is other than hydrogen. 
     
     
       12. A compound of  claim 11  wherein Q 3  is hydrogen. 
     
     
       13. A compound of  claim 11  wherein Q 2  is optionally substituted alkyl. 
     
     
       14. A compound of  claim 13  wherein Q 2  is substituted with hydroxyl or amino. 
     
     
       15. A compound of  claim 10  wherein R 11  is hydrogen. 
     
     
       16. A compound of  claim 10  wherein each R 12  is methyl. 
     
     
       17. A pharmaceutical composition comprising a compound of  claim 10 , or a stereoisomer or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
       18. A method of treating a bacterial infection in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound of  claim 10  or a composition of  claim 17 . 
     
     
       19. A compound of claim 1 wherein Q 1  is 
       
         
           
           
               
               
           
         
        
       
     
     
       20. A compound of claim 1 wherein Q 1  is 
       
         
           
           
               
               
           
         
        
       
     
     
       21. A compound of claim 1 wherein Q 1  is 
       
         
           
           
               
               
           
         
        
       
     
     
       22. A compound of claim 1 wherein Q 1  is 
       
         
           
           
               
               
           
         
       
       or

Cited by (0)

No later patents cite this yet.

References (0)

No backward citations on record.