Boron-containing small molecules

Abstract

This invention provides novel compounds, methods of using the compounds, and pharmaceutical formulations comprising the compounds.

What is claimed is: 
     
         1 .- 20 . (canceled) 
     
     
         21 . A method of treating a disease in an animal comprising:
 contacting the animal with a compound having a structure of formula (I):   
       
         
           
           
               
               
           
         
         wherein
 Y is hydrogen, fluoro, chloro, or bromo; 
 R 1  is phenyl substituted 2-4 times, said substitutions comprising i) 1-4 substitutions with the same or different of halo, and 0-1 substitutions with methyl, difluoromethyl, trifluoromethyl, methoxy, trifluormethoxy, or trifluoroethoxy, or ii) 2 trifluoromethyl groups; 
 R 2  is methyl, fluoromethyl, trifluoromethyl, or perfluoroethyl; 
 R 3a  and R 3b  are independently selected from hydrogen, methyl, ethyl, or fluoromethyl, or R 3a  and R 3b  combine with the carbon to which they are attached to form a cyclopentyl ring or a cyclohexyl ring 
 wherein the animal is in need of treatment thereof; 
 
         or a salt thereof. 
       
     
     
         22 . The method of  claim 21 , wherein the compound has a structure which is: 
       
         
           
           
               
               
           
         
         wherein C* is a carbon atom which is a stereocenter having a (S) configuration. 
       
     
     
         23 . The method of  claim 21 , wherein the compound has a structure which is: 
       
         
           
           
               
               
           
         
       
       wherein
 R 1b , R 1c , and R 1d  are each independently selected from hydrogen, fluoro, chloro, bromo, methyl, difluoromethyl, trifluoromethyl, methoxy, trifluormethoxy, or trifluoroethoxy, and 
 R 3a  and R 3b  are the same and selected from methyl or fluoromethyl. 
 
     
     
         24 . The method of  claim 21 , wherein the compound has a structure which is: 
       
         
           
           
               
               
           
         
       
       wherein R 2  is trifluoromethyl; and R 1b , R 1c , and R 1d  are each independently selected from hydrogen, fluoro, chloro, or bromo. 
     
     
         25 . The method of  claim 24 , wherein R 1b  is fluoro, chloro, or bromo; R 1c  is hydrogen, fluoro, or chloro; and R 1d  is fluoro, chloro, or bromo. 
     
     
         26 . The method of  claim 21 , wherein the compound is selected from
 5-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethyl-benzo[c][1,2]oxaborol-1(3H)-ol;   (S)-5-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethyl benzo[c][1,2]oxaborol-1(3H)-ol;   (R)-5-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dibromophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethyl-benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3-Chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   3,3-Dimethyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethyl-benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichloro-4-methylphenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichloro-4-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydro isoxazol-3-yl)-3,3-dimethyl-benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichloro-4-(difluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydro isoxazol-3-yl)-3,3-dimethyl-benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichloro-4-(trifluoromethoxy)phenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichlorophenyl)-5-(perfluoroethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Bis(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichloro-4-(2,2,2-trifluoroethoxyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   3,3-Dimethyl-5-(5-methyl-5-(3,4,5-trichlorophenyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol;   (S)-3,3-Dimethyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol;   (R)-3,3-Dimethyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3-Chloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(Fluoromethyl)-5-(3,4,5-trichlorophenyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(4-Bromo-3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichloro-4-methoxyphenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,4-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethyl-benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(4-Fluoro-3-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3-Chloro-4,5-difluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,4-Dichloro-5-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dibromo-4-chlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   (S)-5-(5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   (R)-5-(5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(4-Chloro-3,5-difluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   3,3-Dimethyl-5-(5-(trifluoromethyl)-5-(3,4,5-trifluorophenyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dibromo-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   3,3-Bis(fluoromethyl)-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol;   3,3-Dimethyl-5-(5-(2,3,4,5-tetrachlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichloro-2,4-difluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-diethyl-benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1H-spiro[benzo[c][1,2]oxaborole-3,1′-cyclopentan]-1-01;   5-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1H-spiro[benzo[c][1,2]oxaborole-3,1′-cyclohexan]-1-ol;   5-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-4-fluoro-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol;   4-Fluoro-3,3-dimethyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro isoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol;   5-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-6-fluoro-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol; or   6-Fluoro-3,3-dimethyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol, or a salt thereof.   
     
     
         27 . The method of  claim 21 , wherein the compound, or a salt thereof, is
 (R)-3,3-Dimethyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol.   
     
     
         28 . The method of  claim 21 , wherein the compound, or a salt thereof, is
 3,3-Dimethyl-5-(5-(2,3,4,5-tetrachlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol.   
     
     
         29 . The method of  claim 21 , wherein the compound, or a salt thereof, is part of a formulation also comprising at least one pharmaceutically acceptable excipient. 
     
     
         30 . The method of  claim 21 , wherein the disease is rosacea. 
     
     
         31 . The method of  claim 21 , wherein the animal is a human.