Boron-containing small molecules as anti-protozoal agent

• US 8,623,911 B2
• Filed: 03/18/2011
• Issued: 01/07/2014
• Est. Priority Date: 03/19/2010
• Status: Active Grant

• Current Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Original Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Inventors: Jacobs, Robert T., Chen, Daitao, Orr, Matthew, Plattner, Jacob J.
• Primary Examiner(s): SHTERENGARTS, SAMANTHA L
• Application Number:
  US13/636,114
• Publication Number:
  US 20130231304A1
• Time in Patent Office: 1,026 Days
• Field of Search: 514/456, 549/213
• US Class Current: 514/456
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: C07F 5/04 Esters of boric acids
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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.

Claims

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

2. The compound of claim 1, or a salt thereof, wherein Q is C═

O.

3. The compound of claim 1, or a salt thereof, having a structure according to the following formula:

4. The compound of claim 3, or a salt thereof, wherein Y is halo-substituted C₁-C₆ alkyl.

5. The compound of claim 3, or a salt thereof, wherein Y is C₁-C₆ alkyl, substituted with three halogens.

6. The compound of claim 3, or a salt thereof, wherein Y is CF₃.

7. The compound of claim 3, or a salt thereof, wherein the compound is

8. The compound of claim 3, or a salt thereof, wherein the compound is

9. The compound of claim 1, or a salt thereof, having a structure according to the following formula:

10. The compound of claim 1, or a salt thereof, having a structure according to the following formula:

11. The compound of claim 10, or a salt thereof, wherein Y¹ is fluoro or chloro.

12. The compound of claim 10, or a salt thereof, wherein Y is trifluoromethyl.

13. The compound of claim 10, or a salt thereof, which is:

14. The compound of claim 10, or a salt thereof, which is:

15. The compound of claim 10, or a salt thereof, which is:

16. A combination comprising the compound of claim 1, or a salt thereof, together with at least one other therapeutically active agent.

17. A pharmaceutical formulation comprising:

a) the compound of claim 1, or a salt thereof; and

b) a pharmaceutically acceptable excipient.

18. The pharmaceutical formulation of claim 17, wherein the pharmaceutical formulation is a unit dosage form.

19. The pharmaceutical formulation of claim 17, wherein the salt of said compound is a pharmaceutically acceptable salt.

20. A method of killing and/or inhibiting the growth of a protozoa, comprising:

contacting the protozoa with an effective amount of the compound of claim 1, or a salt thereof, thereby killing and/or inhibiting the growth of the protozoa.

21. The method of claim 20, wherein the protozoa is Trypanosoma.

22. The method of claim 20, wherein the protozoa is Trypanosoma brucei.

23. The method of claim 22, wherein the Trypanosoma brucei is a member selected from Trypanosoma brucei brucei, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense.

24. A method of treating a trypanosomiasis in an animal, comprising:

administering to the animal a therapeutically effective amount of the compound of claim 1, or a salt thereof, thereby treating the trypanosomiasis.

25. The method of claim 24, wherein the trypanosomiasis is sleeping sickness.

26. The method of claim 24, wherein the animal is a human.

27. The method of claim 24, wherein the trypanosomiasis is nagana.

28. The method of claim 24, wherein the animal is cattle.