Boron-containing small molecules

1. 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;

wherein the disease is rosacea

or a salt thereof.

2. The method of claim 1 , wherein the compound has a structure which is:

wherein C* is a carbon atom which is a stereocenter having a (S) configuration.

3. The method of claim 1 , 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.

4. The method of claim 1 , 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.

5. The method of claim 4 , wherein R 1b is fluoro, chloro, or bromo; R 1c is hydrogen, fluoro, or chloro; and R 1d is fluoro, chloro, or bromo.

6. The method of claim 1 , 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-(trifluoromethyephenyl)-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-trifluoroethoxy)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)-01;

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-ol;

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.

7. The method of claim 1 , 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.

8. The method of claim 1 , 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.

9. The method of claim 1 , wherein the compound, or a salt thereof, is part of a formulation also comprising at least one pharmaceutically acceptable excipient.

10. The method of claim 1 , wherein the animal is a human.