Boron-containing small molecules

• US 9,145,429 B2
• Filed: 12/18/2013
• Issued: 09/29/2015
• Est. Priority Date: 01/27/2010
• Status: Active Grant

• Current Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Original Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Inventors: Jarnagin, Kurt, Akama, Tsutomu
• Primary Examiner(s): REESE, HEIDI L
• Application Number:
  US14/133,537
• Publication Number:
  US 20140200198A1
• Time in Patent Office: 650 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: A61P 33/12 Schistosomicides
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: C07F 5/04 Esters of boric acids

Abstract

Compounds, pharmaceutical formulations, and methods of treating anti-inflammatory conditions and/or helminth-associated diseases are disclosed.

Claims

1. A method of treating a condition or disease, in an animal, the method comprising administering to the animal a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, having a structure according to a formula which is selected from the group consisting of:

2. The method of claim 1, wherein R^c is chlorine or bromine or iodine.

3. The method of claim 1, wherein R^b is OR⁴, and R⁴ is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

4. The method of claim 1, wherein R^b is OR⁴, and R⁴ is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl and substituted or unsubstituted cycloalkyl.

5. The method of claim 1, wherein the compound, or pharmaceutically acceptable salt thereof, has a structure according to a formula which is selected from the group consisting of

6. The method of claim 1, wherein the condition or disease is a helminth-associated disease which is schistosomiasis.

16. The method of claim 1, wherein said compound is 5-chloro-6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-(2-isopropoxyethoxy)nicotinonitrile.

17. The method of claim 1, wherein said compound is 5-chloro-6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-(4-oxopentyloxy)nicotinonitrile.

7. A method of decreasing the release of a cytokine or a chemokine, the method comprising:

contacting a cell with the compound or a pharmaceutically acceptable salt thereof, having a structure according to a formula which is selected from the group consisting of;

10. The method of claim 7, wherein R^c is chlorine or bromine or iodine.

11. The method of claim 7, wherein R^b is OR⁴, and R⁴ is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

12. The method of claim 7, wherein R^b is OR⁴, and R⁴ is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl and substituted or unsubstituted cycloalkyl.

13. The method of claim 7, wherein the compound, or pharmaceutically acceptable salt thereof, has a structure according to a formula which is selected from the group consisting of

14. The method of claim 7, wherein said compound is 5-chloro-6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-(2-isopropoxyethoxy)nicotinonitrile.

15. The method of claim 7, wherein said compound is 5-chloro-6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-(4-oxopentyloxy)nicotinonitrile.

8. A method of inhibiting a phosphodiesterase (PDE), the method comprising:

contacting the phosphodiesterase with a compound or a pharmaceutically acceptable salt thereof, having a structure according to a formula which is selected from the group consisting of;

9. The method of claim 8, wherein said phosphodiesterase is phosphodiesterase4 (PDE4).

18. The method of claim 8, wherein R^c is chlorine or bromine or iodine.

19. The method of claim 8, wherein R^b is OR⁴, and R⁴ is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

20. The method of claim 8, wherein R^b is OR⁴, and R⁴ is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl and substituted or unsubstituted cycloalkyl.

21. The method of claim 8, wherein the compound, or pharmaceutically acceptable salt thereof, has a structure according to a formula which is selected from the group consisting of

22. The method of claim 8, wherein said compound is 5-chloro-6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-(2-isopropoxyethoxy)nicotinonitrile.

23. The method of claim 8, wherein said compound is 5-chloro-6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-(4-oxopentyloxy)nicotinonitrile.