Boron-containing small molecules

• US 9,353,133 B2
• Filed: 03/07/2014
• Issued: 05/31/2016
• 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, Stephen J., DiPierro, Michael, Hernandez, Vincent S., Hold, Karin M., Kennedy, Isaac, Likhotvorik, Igor, Mao, Weimin, Maples, Kirk, 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:
  US14/201,459
• Publication Number:
  US 20140221631A1
• Time in Patent Office: 816 Days
• Field of Search: 558/294, 558/298, 549/213, 562/7
• US Class Current: 1/1
• 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 compound, or a pharmaceutically acceptable salt thereof, having a structure according to the following formula:

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said R¹ and R² are each members independently selected from H, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted or unsubstituted t-butyl, substituted or unsubstituted phenyl and substituted or unsubstituted benzyl

and wherein R¹ and R², together with the atoms to which they are joined, can optionally form a member selected from substituted or unsubstituted dioxaborolane, substituted or unsubstituted dioxaborinane and substituted or unsubstituted dioxaborepane.

3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein said R¹ and R², together with the atoms to which they are joined, form a member selected from dioxaborolane, substituted or unsubstituted tetramethyldioxaborolane, substituted or unsubstituted phenyldioxaborolane, dioxaborinane, dimethyldioxaborinane and dioxaborepane.

4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z1 is a member selected from

5. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said R^3a is H and R^4a is a member selected from methyl, ethyl, propyl, butyl, phenyl, benzyl and cyano.

6. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is a member selected from

7. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said R¹ and R² are each members independently selected from H, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl.

8. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said R¹ and said R² are each members independently selected from H, methyl, isopropyl, and phenyl.

9. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said R¹ and said R² are methyl.

10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said R¹ and said R² are isopropyl.

11. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said R¹ and said R² are H.

12. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is

13. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is a member selected from: