Treatment of H. pylori infections using MTAN inhibitors
View Patent ↗Methods of treating infections due to Helicobacter pylori ( H. pylori ), in particular in subjects having a peptic ulcer, are disclosed where the methods comprise administering inhibitors of H. pylori MTAN (5′-methylthioadenosine nucleosidase) to the subject, where the inhibitors have the structure
1. A method of treating a Helicobacter pylori ( H. pylori ) infection in a subject comprising administering to the subject a compound in an amount effective to inhibit growth of H. pylori , wherein the compound has the formula
wherein R is Q or CH 2 SQ 1 , wherein Q is C1-C9 alkyl, aryl, heteroaryl, aralkyl, or C4-C7 cycloalkyl, where Q is optionally substituted with one or more halogen, OH and/or NH 2 groups, and wherein Q 1 is C4-C9 alkyl, aryl, heteroaryl, aralkyl, or C4-C7 cycloalkyl, where Q 1 is optionally substituted with one or more halogen, OH and/or NH 2 groups,
or a pharmaceutically acceptable salt thereof, or an ester thereof.
2. The method of claim 1 , wherein R is Q.
3. The method of claim 1 , wherein R is CH 2 SQ 1 .
4. The method of claim 1 , wherein Q is C1-C9 alkyl.
5. The method of claim 1 , wherein Q or Q 1 is C4-C7 cycloalkyl.
6. The method of claim 1 , wherein Q or Q 1 is aryl.
7. The method of claim 1 , wherein Q or Q 1 is heteroaryl.
8. The method of claim 1 , wherein Q or Q 1 is aralkyl.
9. The method of claim 1 , wherein Q or Q 1 is aryl, heteroaryl or aralkyl substituted with a halogen.
10. The method of claim 1 , wherein R is Q, wherein Q is C2-C9 linear alkyl, aryl, heteroaryl, aralkyl, or C4-C7 cycloalkyl, and wherein Q is optionally substituted with one or more halogen, OH and/or NH 2 groups.
11. The method of claim 9 , wherein the halogen is at an ortho, meta or para position.
12. The method of claim 1 , wherein the halogen is Cl, F, Br or I.
13. The method of claim 1 , wherein Q is C3-C9 linear alkyl or heteroaryl.
14. The method of claim 1 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof, or an ester thereof.
15. A method of treating a Helicobacter pylori ( H. pylori ) infection in a subject comprising administering to the subject a compound in an amount effective to inhibit growth of H. pylori , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof, or an ester thereof.
16. The method of claim 1 , wherein the compound is administered in an amount that is effective to inhibit H. pylori 5′-methylthioadenosine nucleosidase (MTAN).
17. The method of claim 1 , wherein the compound inhibits growth of H. pylori but does not inhibit the growth of one or more bacterium selected from the group consisting of E. coli, V. cholerae, S. aureus, K. pneumoniae, S. flexneri, S. enterica and P. aeruginosa.
18. The method of claim 17 , wherein the compound does not inhibit the growth of all of E. coli, V. cholerae, S. aureus, K. pneumoniae, S. flexneri, S. enterica and P. aeruginosa.
19. The method of claim 1 , wherein the compound is more effective in inhibiting growth of H. pylori than amoxicillin, metronidazole or tetracyclin.
20. The method of claim 1 , wherein the subject has a peptic ulcer.
21. The method of claim 1 , wherein the subject has a gastric ulcer or a duodenal ulcer.
22. The method of claim 1 , wherein the compound is administered orally.