Boron-containing small molecules

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.

1 .- 192 . (canceled) 
     
     
         193 . A pharmaceutical formulation comprising:
 a) a pharmaceutically acceptable excipient;   b) a compound that penetrates the nail plate and travels through the nail plate to a nail bed underlying said nail plate; and   c) an emollient which is a cyclic polydimethylsiloxane containing from about 3 to about 9 silicon atoms;   having an efficacy coefficient against a  Trichophyton  species of between about 10 and about 1000;   wherein said pharmaceutical formulation is for ungual administration to an animal suffering from an infection mediated at least in part by said  Trichophyton  species.   
     
     
         194 . The formulation of  claim 193 , wherein the compound is present in said pharmaceutical formulation in a concentration of from about 1% to about 10%. 
     
     
         195 . The formulation of  claim 193 , wherein the cyclic polydimethylsiloxane is cyclomethicone. 
     
     
         196 . The formulation of  claim 193 , further comprising an emollient which is diisopropyl adipate. 
     
     
         197 . The formulation of  claim 193 , wherein the emollient is present in an amount of from about 0.1% to about 15%. 
     
     
         198 . The formulation of  claim 193 , wherein the emollient is present in an amount of from about 10% to about 50%. 
     
     
         199 . The formulation of  claim 193 , wherein said pharmaceutically acceptable excipient is propanol or isopropanol. 
     
     
         200 . The formulation of  claim 193 , wherein said pharmaceutically acceptable excipient is ethanol. 
     
     
         201 . The formulation of  claim 193 , further comprising an antioxidant. 
     
     
         202 . The formulation of  claim 201 , wherein said antioxidant is butylated hydroxytoluene. 
     
     
         203 . The formulation of  claim 201 , wherein said antioxidant is a tocopherol. 
     
     
         204 . The formulation of  claim 203 , wherein said tocopherol is vitamin E. 
     
     
         205 . The formulation of  claim 201 , wherein said antioxidant is present in said pharmaceutical formulation from about 0.001 to 0.5 wt %. 
     
     
         206 . The formulation of  claim 193 , wherein said fungus or yeast is  Trichophyton rubrum  or  Trichophyton mentagrophytes.    
     
     
         207 . The formulation of  claim 193 , wherein the infection is onychomycosis. 
     
     
         208 . The formulation of  claim 193 , wherein the infection is  tinea unguium.    
     
     
         209 . A method of treating an ungual infection in a human, comprising administering to the human a therapeutically effective amount of the pharmaceutical formulation of  claim 193 , sufficient to treat said ungual infection. 
     
     
         210 . The method of  claim 209 , wherein said infection is onychomycosis. 
     
     
         211 . The method of  claim 210 , wherein said onychomycosis is caused by a microorganism, and said administration comprises contacting a dorsal layer of the nail plate of a human nail unit with the compound in the pharmaceutical formulation of  claim 193 , wherein said compound penetrates the nail plate, travels through the nail plate to a nail bed underlying the nail plate, and contacts said microorganism, under conditions sufficient for said compound to penetrate said nail plate and to treat said onychomycosis.