Boron-containing small molecules
This invention relates to, among other items, benzoxaborole compounds and their use for treating bacterial infections.
1. A compound having a structure which is:
wherein R 3 is substituted or unsubstituted nitroalkyl or substituted or unsubstituted aminoalkyl;
R 4 is selected from the group consisting of halogen, unsubstituted alkoxy, and unsubstituted phenyl;
Y is O or S; and
R 5 is selected from the group consisting of substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl;
or a salt, hydrate or solvate thereof.
2. The compound of claim 1 , having a structure which is:
wherein C* is a carbon atom stereocenter which has a configuration which is (R) or (S).
3. The compound of claim 1 , having a structure which is
wherein the C* is a carbon atom stereocenter which has a configuration which is (R) or (S).
4. The compound of claim 2 , wherein the C* stereocenter is in a (S) configuration.
5. The compound of claim 1 , wherein R 3 is —CH 2 NH 2 .
6. The compound of claim 1 , wherein R 4 is selected from the group consisting of fluorine, chlorine, bromine, and iodine.
7. The compound of claim 1 , wherein Y is O.
8. The compound of claim 1 , wherein R 5 is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, and sec-butyl.
9. The compound of claim 1 , wherein R 3 is —CH 2 NH 2 ; and R 4 is halogen.
10. The compound of claim 1 , wherein R 3 is —CH 2 NH 2 ; R 4 is chlorine; Y is O; and R 5 is substituted or unsubstituted alkyl.
11. A composition comprising:
a) a first stereoisomer of the compound of claim 2 ;
b) at least one additional stereoisomer of the first stereoisomer;
wherein the first stereoisomer is present in an enantiomeric excess of at least 80% relative to said at least one additional stereoisomer.
12. A combination comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, together with at least one other therapeutically active agent.
13. A pharmaceutical formulation comprising:
a) the compound of claim 1 , or a pharmaceutically acceptable salt thereof; and
b) a pharmaceutically acceptable excipient.
14. The compound of claim 1 , wherein R 4 is chlorine or bromine.
15. The compound of claim 1 , wherein R 4 is chlorine.
16. The compound of claim 1 , wherein R 4 is selected from the group consisting of methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and sec-butoxy.
17. The compound of claim 1 , wherein R 4 is methoxy or ethoxy.
18. The compound of claim 4 , wherein Y is O.
19. The compound of claim 1 , wherein R 5 is unsubstituted alkyl.
20. The compound of claim 2 , wherein
R 4 is halogen, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is methyl; or
R 4 is halogen, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is ethyl; or
R 4 is halogen, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is propyl; or
R 4 is halogen, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is isopropyl; or
R 4 is halogen, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 4 alkyl; or
R 4 is halogen, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 5 alkyl; or
R 4 is halogen, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 6 alkyl.
21. The compound of claim 2 , wherein
R 4 is halogen, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is methyl; or
R 4 is halogen, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is ethyl; or
R 4 is halogen, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is propyl.
22. The compound of claim 2 , wherein
R 4 is halogen, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is ethyl.
23. The compound of claim 2 , wherein
R 4 is fluorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is methyl; or
R 4 is chlorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is methyl; or
R 4 is bromine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is methyl; or
R 4 is fluorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is ethyl; or
R 4 is chlorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is ethyl; or
R 4 is bromine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is ethyl; or
R 4 is fluorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is propyl;
R 4 is chlorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is propyl;
R 4 is bromine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is propyl;
R 4 is fluorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is isopropyl;
R 4 is chlorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is isopropyl; or
R 4 is bromine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is isopropyl; or
R 4 is fluorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 4 alkyl; or
R 4 is chlorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 4 alkyl; or
R 4 is bromine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 4 alkyl;
R 4 is fluorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 5 alkyl; or
R 4 is chlorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 5 alkyl; or
R 4 is bromine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 5 alkyl; or
R 4 is fluorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 6 alkyl; or
R 4 is chlorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 6 alkyl; or
R 4 is bromine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is unsubstituted C 6 alkyl.
24. The compound of claim 2 , wherein
R 4 is fluorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is ethyl; or
R 4 is chlorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is ethyl; or
R 4 is bromine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is ethyl.
25. The compound of claim 2 , wherein
R 4 is chlorine, R 3 is —CH 2 NH 2 ; Y is O; and R 5 is ethyl.