Boron-containing small molecules

Patent metadata

Field	Value
Publication number	US-9353133-B2
Application number	US-201414201459-A
Country	US
Kind code	B2
Filing date	Mar 7, 2014
Priority date	Feb 16, 2005
Publication date	May 31, 2016
Grant date	May 31, 2016

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.

First claim

What is claimed is:

1. A compound, or a pharmaceutically acceptable salt thereof, having a structure according to the following formula:

in which
R 1 and R 2 are members independently selected from H, 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;
wherein R 1 and R 2 , together with the atoms to which they are attached, can be optionally joined to form a 4- to 7-membered ring;
Z1 is a member selected from

wherein
R 3a and R 4a are members independently selected from H, cyano, 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;
R 5 is a member selected from halogen and OR 8
wherein
R 8 is a member selected from H, 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

R 9a is H, R 11a is H, R 12a is H, R 10a is substituted or unsubstituted phenyloxy, or substituted or unsubstituted pyridinyloxy.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said R 1 and R 2 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 R 1 and R 2 , 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 R 1 and R 2 , 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

and R 5 is a member selected from substituted or unsubstituted methoxy, substituted or unsubstituted ethoxy, substituted or unsubstituted methoxymethoxy, substituted or unsubstituted ethoxyethoxy and substituted or unsubstituted tetrahydro-2H-pyran-2-yloxy.

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 R 1 and R 2 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 R 1 and said R 2 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 R 1 and said R 2 are methyl.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said R 1 and said R 2 are isopropyl.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said R 1 and said R 2 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:

Assignees

• Anacor Pharmaceuticals 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

Classifications

• A61P31/10

  Antimycotics · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• C07F5/025 Primary

  Boronic and borinic acid compounds · CPC title

• C07H19/06

  Pyrimidine radicals · CPC title

• A61K31/69 Primary

  Boron compounds · CPC title