Boron-containing small molecules

• US 8,115,026 B2
• Filed: 12/02/2009
• Issued: 02/14/2012
• Est. Priority Date: 02/16/2005
• Status: Active Grant

• Current Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Original Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Inventors: Baker, Stephen J., Akama, Tsutomu, Alley, Michael Richard Kevin, Benkovic, Steven J., DiPierro, Michael, Hernandez, Vincent S., Hold, Karin M., Kennedy, Isaac, Likhotvorik, Igor, Mao, Weimin, Maples, Kirk R., Plattner, Jacob J., Rock, Fernando, Sanders, Virginia, Stemphoski, Aaron M., Yiannikouros, George Petros, Zegar, Siead, Zhang, Yong-Kang, Zhou, Huchen
• Primary Examiner(s): SHIAO, REI TSANG
• Application Number:
  US12/629,753
• Publication Number:
  US 20100267981A1
• Time in Patent Office: 804 Days
• Field of Search: 558/288
• US Class Current: 558/288
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 9/0012 Galenical forms characterised by the site of application
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: C07F 5/04 Esters of boric acids
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07H 23/00 Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12 esters with inorganic acids C07H11/00; metal salts, see parent 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

This invention relates to compounds useful for treating fungal infections, more specifically topical treatment of onychomycosis and/or cutaneous fungal infections. This invention is directed to compounds that are active against fungi and have properties that allow the compound, when placed in contact with a patient, to reach the particular part of the skin, nail, hair, claw or hoof infected by the fungus. In particular the present compounds have physiochemical properties that facilitate penetration of the nail plate.

Claims

1. A method of making a compound having a structure according to the following formula

2. The method of claim 1, wherein said organic acid is acetic acid.

3. The method of claim 1, wherein said quenching step is essentially not contacted with a strong acid.

4. The method of claim 1 wherein said compound is purified by recrystallization from a recrystallization solvent, wherein said recrystallization solvent essentially does not contain acetonitrile.

5. The method of claim 4, wherein said recrystallization solvent comprises toluene and heptane.

6. The method of claim 4, wherein said recrystallization solvent contains a member selected from less than 2% acetonitrile, less than 1% acetonitrile, less than 0.5% acetonitrile, and less than 0.1% acetonitrile.

7. The method of claim 4, wherein the recrystallization solvent contains toluene and a hydrocarbon solvent.

8. The method of claim 7, wherein the recrystallization solvent contains a member selected from about 1:

1 toluene;

hydrocarbon solvent, about 2;

1 toluene;

hydrocarbon solvent, about 3;

1 toluene;

hydrocarbon solvent, and about 4;

1 toluene;

hydrocarbon solvent.

9. The method of claim 7, wherein the hydrocarbon solvent is a member selected from heptane, octane, hexane, pentane and nonane.

10. The method of claim 5, wherein the recrystallization solvent is 3:

1 toluene;

heptane.

11. The method of claim 1 wherein said trialkyl borate is a member selected from trimethyl borate, triisopropyl borate, and tributyl borate.

12. The method of claim 1 wherein said trialkyl borate is trimethyl borate.