Boron-containing small molecules as antiprotozoal agents

Patent metadata

Field	Value
Publication number	US-9346834-B2
Application number	US-201013503016-A
Country	US
Kind code	B2
Filing date	Oct 19, 2010
Priority date	Oct 20, 2009
Publication date	May 24, 2016
Grant date	May 24, 2016

Abstract

This invention provides, among other things, novel compounds useful for treating protozoal infections, pharmaceutical compositions containing such compounds, as well as combinations of these compounds with at least one additional therapeutically effective agent.

First claim

What is claimed is:

1. A compound having a structure according to the following formula:

or a salt, hydrate, or solvate thereof,
wherein
R 2 is selected from the group consisting of unsubstituted linear alkylene, alkylene substituted with unsubstituted alkyl, alkylene substituted with unsubstituted aryl;
R 3 is selected from the group consisting of halosubstituted alkyl, unsubstituted cycloalkyl, halosubstituted or unsubstituted heteroaryl, vinyl, C(O)H,
—C(O)R 12 , C(O)NHR 14 , and —OR 10

wherein
R 10 is selected from the group consisting of unsubstituted alkyl, and unsubstituted heterocycloalkyl;
R 12 is unsubstituted alkyl; and
R 14 is selected from the group consisting of H, unsubstituted alkyl, substituted aryl, substituted and unsubstituted arylalkyl and unsubstituted cycloalkyl.

2. The compound of claim 1 , or a salt, hydrate, or solvate thereof, wherein R 3 is —C(O)R 12 and R 2 is unsubstituted linear alkylene and R 12 is unsubstituted alkyl.

3. The compound of claim 1 , or a salt, hydrate, or solvate thereof, wherein R 3 is —C(O)R 12 and R 2 is methylene and R 12 is unsubstituted alkyl.

4. The compound of claim 1 , or a salt, hydrate, or solvate thereof, wherein the compound has the following structure:

5. The compound of claim 4 , or a salt, hydrate, or solvate thereof, wherein R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl or unsubstituted C 5 alkyl or unsubstituted C 6 alkyl.

6. The compound of claim 4 , or a salt, hydrate, or solvate thereof, wherein R 2 is methylene or ethylene or propylene or butylene or pentylene or hexylene.

7. The compound of claim 4 , or a salt, hydrate, or solvate thereof, wherein R 2 is methylene and R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl.

8. The compound of claim 4 , or a salt, hydrate, or solvate thereof, wherein R 2 is ethylene and R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl.

9. The compound of claim 4 , or a salt, hydrate, or solvate thereof, wherein R 2 is propylene and R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl.

10. The compound of claim 1 , or a salt, hydrate, or solvate thereof, wherein the compound has the following structure:

wherein R 4 is C 1 -C 6 unsubstituted alkyl.

11. The compound of claim 10 , or a salt, hydrate, or solvate thereof, wherein R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl or unsubstituted C 5 alkyl or unsubstituted C 6 alkyl.

12. The compound of claim 10 , or a salt, hydrate, or solvate thereof, wherein R 4 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl or unsubstituted C 5 alkyl or unsubstituted C 6 alkyl.

13. The compound of claim 10 , or a salt, hydrate, or solvate thereof, wherein R 4 is methyl and R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl.

14. The compound of claim 10 , or a salt, hydrate, or solvate thereof, wherein R 4 is methyl and R 12 is methyl.

15. The compound of claim 10 , or a salt, hydrate, or solvate thereof, wherein R 4 is ethyl and R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl.

16. The compound of claim 10 , or a salt, hydrate, or solvate thereof, wherein R 4 is propyl and R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl.

17. The compound of claim 10 , or a salt, hydrate, or solvate thereof, wherein R 4 is isopropyl and R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl.

18. The compound of claim 1 , or a salt, hydrate, or solvate thereof, wherein the compound has the following structure:

wherein R 4 is C 1 -C 6 unsubstituted alkyl and R 5 is C 1 -C 6 unsubstituted alkyl.

19. The compound of claim 18 , or a salt, hydrate, or solvate thereof, wherein R 12 is methyl or ethyl or unsubstituted C 3 alkyl.

20. The compound of claim 18 , or a salt, hydrate, or solvate thereof, wherein R 4 is methyl, and R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl or unsubstituted C 5 alkyl or unsubstituted C 6 alkyl.

21. The compound of claim 18 , or a salt, hydrate, or solvate thereof, wherein R 4 is ethyl, and R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl or unsubstituted C 5 alkyl or unsubstituted C 6 alkyl.

22. The compound of claim 18 , or a salt, hydrate, or solvate thereof, wherein R 4 is unsubstituted C 3 alkyl, and R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl or unsubstituted C 5 alkyl or unsubstituted C 6 alkyl.

23. The compound of claim 18 , or a salt, hydrate, or solvate thereof, wherein R 4 is methyl, R 5 is methyl and R 12 is methyl or ethyl or unsubstituted C 3 alkyl of unsubstituted C 4 alkyl or unsubstituted C 5 alkyl or unsubstituted C 6 alkyl.

24. The compound of claim 18 , or a salt, hydrate, or solvate thereof, wherein R 4 is methyl, R 5 is methyl and R 12 is methyl or ethyl or unsubstituted C 3 alkyl.

25. The compound of claim 18 , or a salt, hydrate, or solvate thereof, wherein R 4 is ethyl, R 5 is ethyl and R 12 is methyl or ethyl or unsubstituted C 3 alkyl or unsubstituted C 4 alkyl or unsubstituted C 5 alkyl or unsubstituted C 6 alkyl.

26. The compound of claim 1 , or a salt, hydrate, or solvate thereof, which is methyl [2-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)]acetamide, ethyl [2-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)]acetamide, N-propyl-2-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)acetamide, N-tert-butyl-2-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)acetamide, or N-(2,6-dimethylphenyl)-[2-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)]acetamide.

27. The compound of claim 4 , or a salt, hydrate, or solvate thereof, which is 1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy) butan-2-one, 1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy) pentan-2-one, 1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)-4-methylpentan-2-one, 3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy) butan-2-one, 2-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy) pentan-3-one, 3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy) pentan-2-one, 3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy) hexan-2-one, 3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy) heptan-4-one, 3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)-4-methyl-pentan-2-one, 3-(1,3-dihydro-1-hydroxyl-2,1-benzoxaborol-6-yloxy)-3-methylbutan-2-one, or 6-(2-hydroxy-1-methylbutoxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole.

28. The compound of claim 1 , or a salt, hydrate, or solvate thereof, which is 6-((2′-chloro)thiazol-5-yl)methoxy-1,3-dihydro-1-hydroxy-2,1-benzoxaborole, 6-((3,5-dimethylisoxazol-4-yl)methoxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole, 6-((isoindoline-1,3-dione-2-yl)propoxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole, 6-(2-(1H-tetrazol-5-yl)

Assignees

• Zhou Huchen
• Ding Dazhong
• Sun Daoan
• Zhou Yasheen
• Zhang Yong-Kang
• Plattner Jacob J
• Anacor Pharmaceuticals Inc

Inventors

• Zhou Huchen
• Ding Dazhong
• Sun Daoan
• Zhou Yasheen
• Zhang Yong-Kang
• Plattner Jacob J

Classifications

• C07F5/025 Primary

  Boronic and borinic acid compounds · CPC title

• A61P33/02

  Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis · CPC title