Metalloenzyme inhibitor compounds

1. A compound of Formula I, or salt thereof, wherein:

MBG is optionally substituted tetrazolyl, optionally substituted triazolyl, or optionally substituted pyrazolyl;

R 1 is H, halo, alkyl or haloalkyl;

R 2 is H, halo, alkyl or haloalkyl;

R 3 is independently cycloalkyl, alkoxyalkyl, haloalkoxyalkyl, aryloxyalkyl, thioalkyl, hydroxyl, halothioalkyl, thiocyanate, —S(O) 2 R 7 , nitro, —C(O)CF 3 , —C(O)OR 7 , —C(O)NR 7 R 8 , amino, or cyclic amino;

R 4 is aryl, heteroaryl or cycloalkyl, optionally substituted with 0, 1, 2 or 3 independent halo;

R 5 is H, —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)alkyl optionally substituted with amino;

R 6 is halo, alkyl, haloalkyl or haloalkoxy;

R 7 is alkyl or cycloalkyl;

R 8 is alkyl or haloalkyl; and

n is 0, 1, 2 or 3.

2. The compound of claim 1 , or salt thereof, wherein R 1 is fluoro.

3. The compound of claim 1 , or salt thereof, wherein R 2 is fluoro.

4. The compound of claim 1 , or salt thereof, wherein R 1 and R 2 are fluoro.

5. The compound of claim 1 , or salt thereof, wherein R 1 is alkyl.

6. The compound of claim 1 , or salt thereof, wherein R 1 is methyl.

7. The compound of claim 1 , or salt thereof, wherein R 3 is independently cycloalkyl, alkoxyalkyl, haloalkoxyalkyl, aryloxyalkyl, thioalkyl, thiocyanate, —S(O) 2 R 7 , nitro, —C(O)CF 3 , —C(O)OR 7 , —C(O)NR 7 R 8 , amino, or cyclic amino.

8. The compound of claim 1 , or salt thereof, wherein n is 1, 2 or 3.

9. The compound of claim 1 , or salt thereof, wherein R 5 is H.

10. The compound of claim 1 , or salt thereof, wherein R 5 is —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)alkyl optionally substituted with amino.

11. The compound of claim 1 , or salt thereof, wherein R 1 is methyl and R 2 is fluoro.

12. The compound of claim 10 , or salt thereof, wherein R 3 is independently cycloalkyl, alkoxyalkyl, haloalkoxyalkyl, aryloxyalkyl, thioalkyl, thiocyanate, —S(O) 2 R 7 , nitro, —C(O)CF 3 , —C(O)OR 7 , —C(O)NR 7 R 8 , amino, or cyclic amino.

13. The compound of claim 1 , or salt thereof, wherein R 1 is methyl, R 2 is fluoro, and R 3 is independently H, alkyl, cyano, haloalkyl, alkoxy, halo, or haloalkoxy.

14. A method of inhibiting the activity of a metalloenzyme comprising: contacting said metalloenzyme with an effective amount of the compound of claim 1 , or salt thereof, wherein the metalloenzyme is lanosterol demethylase (CYP51).

15. A compound of Formula I, or salt thereof, wherein:

MBG is optionally substituted tetrazolyl, optionally substituted triazolyl, or optionally substituted pyrazolyl;

R 1 is halo;

R 2 is halo;

R 3 is independently H, alkyl, cyano, haloalkyl, alkoxy, halo, haloalkoxy, cycloalkyl, alkoxyalkyl, haloalkoxyalkyl, aryloxyalkyl, thioalkyl, hydroxyl, halothioalkyl, thiocyanate, —S(O) 2 R 7 , nitro, —C(O)CF 3 , —C(O)OR 7 , —C(O)NR 7 R 8 , amino, cyclic amino, —NHC(O)CF 3 , or —OCF 2 C(O)OR 7 ;

R 4 is aryl, heteroaryl or cycloalkyl, optionally substituted with 0, 1, 2 or 3 groups each independently selected from the group consisting of cycloalkyl, alkoxyalkyl, haloalkoxyalkyl, aryloxyalkyl, thioalkyl, thiocyanate, —S(O) 2 R 7 , nitro, —C(O)CF 3 , —C(O)OR 7 , —C(O)NR 7 R 8 , amino, and cyclic amino, —NHC(O)CF 3 , and —OCF 2 C(O)OR 7 ;

R 5 is —P(O)(OH) 2 or —CH 2 —O—P(O)(OH) 2 ;

R 6 is hydrogen, halo, alkyl, haloalkyl or haloalkoxy;

R 7 is hydrogen, alkyl or cycloalkyl;

R 8 is hydrogen, alkyl or haloalkyl; and

n is 0, 1, 2 or 3.

16. A compound of Formula I, or salt thereof, wherein:

MBG is optionally substituted tetrazolyl, optionally substituted triazolyl, or optionally substituted pyrazolyl;

R 1 is halo;

R 2 is halo;

R 3 is independently cycloalkyl, alkoxyalkyl, haloalkoxyalkyl, aryloxyalkyl, thioalkyl, hydroxyl, thiocyanate, —S(O) 2 R 7 , nitro, —C(O)CF 3 , —C(O)OR 7 , —C(O)NR 7 R 8 , amino, cyclic amino, —NHC(O)CF 3 , or —OCF 2 C(O)OR 7 ;

R 4 is aryl, heteroaryl, or cycloalkyl, optionally substituted with 0, 1, 2 or 3 independent halo;

R 5 is H, —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)alkyl optionally substituted with amino;

R 6 is H, halo, alkyl, haloalkyl or haloalkoxy;

R 7 is H, alkyl or cycloalkyl;

R 8 is H, alkyl or haloalkyl; and

n is 0, 1, 2 or 3.

17. A compound of Formula I, or salt thereof, wherein:

MBG is optionally substituted tetrazolyl, optionally substituted triazolyl, or optionally substituted pyrazolyl;

R 1 is H, halo, alkyl or haloalkyl;

R 2 is H, alkyl or haloalkyl;

R 3 is independently H, alkyl, cyano, haloalkyl, alkoxy, halo, haloalkoxy, cycloalkyl, alkoxyalkyl, haloalkoxyalkyl, aryloxyalkyl, thioalkyl, hydroxyl, halothioalkyl, thiocyanate, —S(O) 2 R 7 , nitro, —C(O)CF 3 , —C(O)OR 7 , —C(O)NR 7 R 8 , amino, cyclic amino, —NHC(O)CF 3 , or —OCF 2 C(O)OR 7 ;

R 4 is aryl, heteroaryl, or cycloalkyl, optionally substituted with 0, 1, 2 or 3 groups each independently selected from the group consisting of H, alkyl, cyano, haloalkyl, alkoxy, halo, haloalkoxy, cycloalkyl, alkoxyalkyl, haloalkoxyalkyl, aryloxyalkyl, thioalkyl, thiocyanate, —S(O) 2 R 7 , nitro, —C(O)CF 3 , —C(O)OR 7 , —C(O)NR 7 R 8 , amino, and cyclic amino;

R 5 is H, —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)alkyl optionally substituted with amino;

R 6 is H, halo, alkyl, haloalkyl or haloalkoxy;

R 7 is H, alkyl or cycloalkyl;

R 8 is H, alkyl or haloalkyl; and

n is 0, 1, 2 or 3.

18. The compound, which is selected from the group consisting of:

1-(5-(4-(tert-Butoxy)phenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (28);

1-(5-(4-Chloro-3-fluorophenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (29);

3-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenol (30);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(3-(trifluoromethyl)phenyl)pyridin-2-yl)propan-2-ol (31);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(4-nitrophenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (32);

1-(4-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)-2,2,2-trifluoroethanone (33);

2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(trifluoromethoxy)phenyl)pyridin-2-yl)propan-2-ol (34);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-phenylpyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (35);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(4-morpholinophenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (36);

N-(4-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)-2,2,2-trifluoroacetamide (37);

1-(5-(4-(Difluoromethoxy)phenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (38);

1-(5-(4-((Difluoromethyl)thio)phenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (40);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(2,2,2-trifluoroethyl)phenyl)pyridin-2-yl)propan-2-ol (41);

4-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)-N-methylbenzamide (42);

Ethyl 2-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenoxy)-2,2-difluoroacetate (43);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(3,3,3-trifluoropropoxy)phenyl)pyridin-2-yl)propan-2-ol (44);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-((2,2,2-trifluoroethyl)thio)phenyl)pyridin-2-yl)propan-2-ol (45);

2-(2,4-Difluorophenyl)-3-fluoro-1-(1H-tetrazol-1-yl)-3-(5-(4-(trifluoromethoxy)phenyl)pyridin-2-yl)butan-2-ol (46);

2-(2,4-Difluorophenyl)-3-fluoro-3-(5-(4-fluorophenyl)pyridin-2-yl)-1-(2H-tetrazol-2-yl)butan-2-ol (48);

2-(2,4-Difluorophenyl)-3-fluoro-3-(5-(4-fluorophenyl)pyridin-2-yl)-1-(1H-tetrazol-1-yl)butan-2-ol (50);

2-(2,4-Difluorophenyl)-3-fluoro-1-(1H-tetrazol-1-yl)-3-(5-(4-(trifluoromethyl)phenyl)pyridin-2-yl)butan-2-ol (52);

3-(5-(4-Chlorophenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-3-fluoro-1-(1H-tetrazol-1-yl)butan-2-ol (54);

2-(2,4-Difluorophenyl)-3-fluoro-1-(1H-tetrazol-1-yl)-3-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)butan-2-ol (56); and

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-yl dihydrogen phosphate (58); and

salts thereof and diastereomers thereof.