Boron-containing small molecules

• US 9,796,735 B2
• Filed: 11/07/2014
• Issued: 10/24/2017
• Est. Priority Date: 06/20/2007
• Status: Active Grant

• Current Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Original Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Inventors: Baker, Stephen J., Hernandez, Vincent S., Sharma, Rashmi, Nieman, James A., Akama, Tsutomu, Zhang, Yong-Kang, Plattner, Jacob J., Alley, Michael Richard Kevin, Singh, Rajeshwar, Rock, Fernando
• Primary Examiner(s): Otton, Alicia L
• Application Number:
  US14/536,483
• Publication Number:
  US 20150133402A1
• Time in Patent Office: 1,082 Days
• Field of Search: None
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/02 Local antiseptics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• 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

The compounds are of the class of 3,7 substituted benzoxaboroles, useful for killing and/or inhibiting the growth of microorganisms.

Claims

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

2. The compound of claim 1, having a structure according to the following formula:

5. The compound of claim 1 or claim 3, wherein the salt is a pharmaceutically acceptable salt.

6. A composition comprising:

a) a first stereoisomer of the compound of claim 2 or claim 4, wherein R³ is not H;

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.

7. A composition comprising the compound of claim 2 or claim 4, wherein the C* stereocenter is in a (S) configuration, and said composition is substantially free of the enantiomer of the compound.

8. A combination comprising the compound of claim 1 or claim 3, or a pharmaceutically acceptable salt thereof, together with at least one additional compound which is selected from the group consisting of an antimicrobial, an immune therapy, a therapeutic vaccine, an antifibrotic agent, an antiinflammatory agent, a bronchodilator, a mucolytic agent, an anti-muscarinic, an anti-leukotriene, an inhibitor of cell adhesion, an anti-oxidant, a cytokine agonist, a cytokine antagonist, and a lung surfactant.

9. A pharmaceutical formulation comprising:

a) the compound of claim 1 or claim 3, or a pharmaceutically acceptable salt thereof; and

b) a pharmaceutically acceptable excipient.

10. The pharmaceutical formulation of claim 9 wherein the pharmaceutical formulation is a unit dosage form.

11. The combination of claim 8, or a pharmaceutically acceptable salt thereof, wherein the antimicrobial is an antibacterial.

12. A method of inhibiting a bacterial or fungal leucyl tRNA synthetase enzyme, comprising:

contacting the bacterial or fungal leucyl tRNA synthetase enzyme with the compound of claim 1 or claim 3, thereby inhibiting the bacterial or fungal leucyl tRNA synthetase enzyme.

13. A method of treating a bacterial-associated or fungal-associated disease in an animal, comprising:

administering to the animal a therapeutically effective amount of the compound of claim 1 or claim 3, or a pharmaceutically acceptable salt thereof, thereby treating the bacterial-associated or fungal-associated disease.

14. The method of claim 13, wherein the animal is a human.

3. A compound having a structure according to a formula which is selected from the group consisting of:

4. The compound of claim 3, having a structure according to a formula which is selected from the group consisting of: