Metalloenzyme inhibitor compounds

1. A method of treating a subject suffering from Cryptococcosis, comprising administering to said subject in need thereof, an effective amount of a compound of formula (I) or salt thereof, wherein:

R 1 is halo;

R 2 is halo;

each R 3 is independently cyano, haloalkyl, alkoxy, halo, haloalkoxy, hydroxy, amino, —NR 6 R 9 , —SR 10 , —C(O)R 10 , optionally substituted haloalkyl, optionally substituted arylalkoxy, —C(O)NR 6 R 7 , —CH(OH)-haloalkyl, optionally substituted alkyl, hydroxyalkyl, alkoxyalkyl, isocyano, cycloalkylaminocarbonyl, optionally substituted aryloxyalkyl, optionally substituted arylalkylthio, haloalkylthio, optionally substituted arylalkylsulfonyl, optionally substituted arylalkylsulfinyl, optionally substituted heteroarylalkoxy, optionally substituted arylthioalkyl, or haloalkylcarbonyl;

n is 0, 1, 2 or 3;

R 4 is aryl optionally substituted with 0, 1, 2 or 3 independent R 8 ;

R 5 is H, alkyl, phosphato, phosphito, alkoxyphosphato, or —C(O)alkyl optionally substituted with 1 or 2 amino;

R 6 is independently H or alkyl;

R 7 is independently H, optionally substituted alkyl, optionally substituted haloalkyl or optionally substituted arylalkyl;

each R 8 is independently cyano, haloalkyl, alkoxy, halo, or haloalkoxy;

each R 9 is independently H, alkyl, —C(O)alkyl, —C(O)H, —C(O)haloalkyl, optionally substituted arylalkyl, or optionally substituted haloalkyl;

each R 10 is independently H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heterocycloalkyl, or optionally substituted arylalkyl;

Ar 2 is

R 11 is optionally substituted phenyl, optionally substituted alkyl, optionally substituted thienyl, pyrrolyl, furanyl, optionally substituted pyridyl, —CH(OH)-alkyl, —CH(OH)-haloalkyl, optionally substituted arylalkyl, optionally substituted aryloxyalkyl, haloalkyl, haloalkoxyalkyl, optionally substituted indolyl, optionally substituted benzofuranyl, heterocycloalkyl, or

R 12 is R 4 , —C(O)R 4 , —C(O)R 7 , —SO 2 R 4 ;

MBG is optionally substituted tetrazolyl, optionally substituted triazolyl, optionally substitute oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl.

2. The method of claim 1 , wherein the disorder or disease is associated with Cryptococcus neoformans.

3. The method of claim 1 , wherein the subject is an animal other than a human.

4. The method of claim 1 , wherein the subject is a human.

5. The method of claim 1 , wherein R 1 is fluoro.

6. The method of claim 1 , wherein R 2 is fluoro.

7. The method of claim 1 , wherein R 1 and R 2 are fluoro.

8. The method of claim 1 , wherein R 4 is phenyl optionally substituted with 0, 1, 2 or 3 independent R 8 .

9. The method of claim 1 , wherein R 4 is phenyl optionally substituted with 0, 1, 2 or 3 independent halo.

10. The method of claim 1 , wherein R 4 is phenyl optionally substituted with 0, 1, 2 or 3 independent fluoro.

11. The method of claim 1 , wherein R 4 is 2,4-difluorophenyl.

12. The method of claim 1 , wherein R 5 is H.

13. The method of claim 1 , wherein R 5 is amino substituted acyl.

14. The method of claim 1 , wherein R 5 is phosphato.

15. The method of claim 1 , wherein:

R 1 is fluoro;

R 2 is fluoro;

R 4 is 2,4-difluorophenyl;

R 5 is H;

Ar 2 is

and

MBG is 1-tetrazolyl.

16. The method of claim 15 , wherein:

R 11 is phenyl, thienyl, arylalkyl, aryloxyalkyl, each optionally substituted with independent R 3 ;

each R 3 is independently cyano, haloalkyl, halo, haloalkoxy, optionally substituted arylalkoxy, haloalkylaminocarbonyl, optionally substituted arylalkylaminocarbonyl; and

n is 1 or 2.

17. The method of claim 15 , wherein:

R 11 is phenyl, thienyl, arylalkyl, aryloxyalkyl, each optionally substituted with independent R 3 ;

each R 3 is independently cyano, haloalkyl, halo, haloalkoxy, optionally substituted arylalkoxy, haloalkylaminocarbonyl, optionally substituted arylalkylaminocarbonyl; and

n is 1.

18. The method of claim 15 , wherein:

R 11 is phenyl optionally substituted with independent R 3 ;

each R 3 is independently cyano, haloalkyl, halo; and

n is 1 or 2.

19. The method of claim 15 , wherein:

R 11 is thienyl optionally substituted with independent R 3 ;

each R 3 is independently haloalkylaminocarbonyl, optionally substituted arylalkylaminocarbonyl; and

n is 1 or 2.

20. The method of claim 1 , wherein the compound is one of:

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

1-(5-((4-Chlorophenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (2);

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

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

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

5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl) ethynyl)-N-(4-fluorobenzyl)thiophene-2-carboxamide (6);

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl) propyl) pyridin-3-yl) ethynyl) phenoxy) methyl)-2-fluorobenzonitrile (7);

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzonitrile (8);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(2,2,2-trifluoro-1-hydroxyethyl) phenyl) ethynyl) pyridin-2-yl)propan-2-ol (9);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-((1-methyl-1H-pyrrol-3-yl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (10);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-((4-fluorophenyl)ethynyl)thiophen-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (11);

2-(2,4-Difluorophenyl)-1-(6-((3,4-difluorophenyl)ethynyl)pyridazin-3-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (12);

4-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)but-3-yn-2-ol (13);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((5-(2,2,2-trifluoro-1-hydroxyethyl)thiophen-2-yl)ethynyl)pyridin-2-yl)propan-2-ol (14);

2-(2,4-difluorophenyl)-1-(5-((3,4-difluorophenyl)ethynyl)pyrazin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (15);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((5-(2,2,2-trifluoro-1-hydroxy ethyl)furan-2-yl)ethynyl)pyridin-2-yl)propan-2-ol (16);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(3-(3-fluorophenyl)prop-1-yn-1-yl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (17);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(3-(4-fluorophenoxy)prop-1-yn-1-yl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (18);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-((1-(4-fluorophenyl)piperidin-4-yl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (19);

1-(5-((4-((4-Cyanobenzyl)oxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl) propan-2-yl dihydrogen phosphate (20);

1-(5-((3-chlorophenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (21);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((2-fluoro-4-(trifluoromethyl)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (22);

2-(2,4-difluorophenyl)-1-(5-(3,3-difluoroprop-1-ynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (23);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((2-fluorophenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (24);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((3-fluorophenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (25);

1-(5-((4-(difluoromethyl)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (26);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((2-fluoro-4-methylphenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (27);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((3-fluoropyridin-2-yl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (28);

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

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((5-(trifluoromethyl)thiophen-2-yl)ethynyl)pyridin-2-yl)propan-2-ol (30);

2-(2,4-difluorophenyl)-1-(5-((3,5-difluoropyridin-2-yl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (31);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((5-fluoropyridin-2-yl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (32);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((6-fluoropyridin-3-yl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (33);

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

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((2-fluoro-4-methoxyphenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (35);

2-(2,4-difluorophenyl)-1-(5-((2,6-difluorophenyl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (36);

2-(2,4-difluorophenyl)-1-(5-((3,4-difluorophenyl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (37);

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

1-(5-((4-(1,1-difluoroethyl)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (39);

1-(5-((4-(difluoromethoxy)phenyl)ethynyl)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-(trifluoromethylthio)phenyl)ethynyl)pyridin-2-yl)propan-2-ol (41);

1-(5-((4-chloro-3-fluorophenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (42);

2-(4-chloro-2-fluorophenyl)-1,1-difluoro-1-(5-((4-fluorophenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (43);

1,1-difluoro-2-(2-fluoro-4-(trifluoromethyl)phenyl)-1-(5-((4-fluorophenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (44);

2-(2,5-difluorophenyl)-1,1-difluoro-1-(5-((4-fluorophenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (45);

2-(3,4-difluorophenyl)-1,1-difluoro-1-(5-((4-fluorophenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (46);

1-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenyl)ethanone (47);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(6-((4-fluorophenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (48);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(6-((4-fluorophenyl)ethynyl)pyridazin-3-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (49);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(hydroxymethyl)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (50);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(methoxymethyl)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (51);

4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)-1,1,1-trifluorobut-3-yn-2-ol (52);

1-(5-((5-bromothiophen-2-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (53);

1-(5-((5-(difluoromethyl)thiophen-2-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (54);

1-(5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)thiophen-2-yl)-2,2,2-trifluoroethanone (55);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl)ethynyl)pyridin-2-yl)propan-2-ol (56);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(3-(2,2,2-trifluoroethoxy)prop-1-ynyl)pyridin-2-yl)propan-2-ol (57);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(thiophen-2-ylethynyl)pyridin-2-yl)propan-2-ol (58);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((2-fluoro-4-(methylamino)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (59);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(methylamino)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (60);

2-(2,4-difluorophenyl)-1-(5-((3,4-difluorophenyl)ethynyl)thiophen-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (61);

2-(2,4-difluorophenyl)-1-(5-((4-(dimethylamino)phenyl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (62);

1-(5-((1H-pyrrol-3-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (63);

1-(5-((4-(difluoromethyl)-3-fluorophenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (64);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(3-(3-fluorophenyl)prop-1-ynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (65);

1-(5-((1-(difluoromethyl)-1H-pyrrol-3-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (66);

2-(2,4-difluorophenyl)-1-(5-((2,5-difluorophenyl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (67);

N-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenyl)formamide (68);

4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)benzonitrile (69);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-isocyanophenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (70);

3-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)benzonitrile (71);

1-(5-((5-bromofuran-2-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (72);

4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)-3-fluorobenzonitrile (73);

4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)-2-fluorobenzonitrile (74);

3-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)-4-fluorobenzonitrile (75);

1-(5-((5-(difluoromethyl)furan-2-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (76);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((5-(2,2,2-trifluoroethyl)thiophen-2-yl)ethynyl)pyridin-2-yl)propan-2-ol (77);

1-(5-((4-aminophenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (78);

N-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenyl)-2,2,2-trifluoroacetamide (79);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(2,2,2-trifluoroethylamino)phenyl)ethynyl)pyridin-2-yl)propan-2-ol (80);

4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenol (81);

4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)benzamide (82);

1-(5-((4-amino-2-fluorophenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (83);

N-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenyl)acetamide (84);

1-(5-(3-(2,4-difluorophenoxy)prop-1-ynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (85);

4-(3-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)prop-2-ynyloxy)benzonitrile (86);

1-(5-((1H-indol-5-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (87);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-fluorobenzylamino)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (88);

1-(5-(benzofuran-5-ylethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (89);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(2,2,2-trifluoroethyl)phenyl)ethynyl)pyridin-2-yl)propan-2-ol (90);

4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)-N-(2,2,2-trifluoroethyl)benzamide (91);

(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenyl)(pyrrolidin-1-yl)methanone (92);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-fluorobenzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (93);

5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide (94);

(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)piperidin-1-yl)(4-fluorophenyl)methanone (95);

1-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)piperidin-1-yl)-2,2,2-trifluoroethanone (96);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((3-(2,2,2-trifluoroethoxy)phenyl)ethynyl)pyridin-2-yl)propan-2-ol (97);

3-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)-N-(2,2,2-trifluoroethyl)benzamide (98);

1,1-difluoro-2-(4-fluorophenyl)-1-(5-((4-fluorophenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (99);

3-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzonitrile (100);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(4-(trifluoromethoxy)benzyloxy)phenyl)ethynyl)pyridin-2-yl)propan-2-ol (101);

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)-3-fluorobenzonitrile (102);

3-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)-4-fluorobenzonitrile (103);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(3-(trifluoromethoxy)benzyloxy)phenyl)ethynyl)pyridin-2-yl)propan-2-ol (104);

1-(5-((4-(2,4-difluorobenzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (105);

1-(5-((4-(3,4-difluorobenzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (106);

1-(5-((4-(4-chlorobenzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (107);

1-(5-((4-(4-chloro-2-fluorobenzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (108);

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)-N-methylbenzamide (109);

6-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)nicotinonitrile (110);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(thiazol-2-ylmethoxy)phenyl)ethynyl)pyridin-2-yl)propan-2-ol (111);

5-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)-2-fluorobenzonitrile (112);

1-(5-((4-(2,3-difluorobenzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (113);

1-(5-(3-(4-chlorophenoxy)prop-1-ynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (114);

4-(3-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)prop-2-ynyloxy)-3-fluorobenzonitrile (115);

4-(3-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)prop-2-ynyloxy)-2-fluorobenzonitrile (116);

1-(5-(3-(4-chloro-2-fluorophenoxy)prop-1-ynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (117);

1-(5-(3-(4-(difluoromethyl)phenoxy)prop-1-ynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (118);

5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)-N-(3-fluorobenzyl)thiophene-2-carboxamide (119);

N-(3-cyanobenzyl)-5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)thiophene-2-carboxamide (120);

N-(4-cyanobenzyl)-5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)thiophene-2-carboxamide (121);

5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)-N-(4-(trifluoromethyl)benzyl)thiophene-2-carboxamide (122);

(5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)thiophen-2-yl)(morpholino)methanone (123);

(5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)thiophen-2-yl)(pyrrolidin-1-yl)methanone (124);

5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)-N-(4-(methylsulfonyl)benzyl)thiophene-2-carboxamide (125);

3-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)-2-fluorobenzonitrile (126);

3-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)-5-fluorobenzonitrile (127);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(piperidin-4-ylethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (128);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((1-(4-fluorophenylsulfonyl)piperidin-4-yl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (129);

1-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenyl)-2,2,3,3,3-pentafluoropropan-1-ol (130);

4-((4-((6-(2-(2,5-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)-2-fluorobenzonitrile (131);

4-((4-((6-(2-(4-chloro-2-fluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)-2-fluorobenzonitrile (132);

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenylthio)methyl)-2-fluorobenzonitrile (133);

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenylsulfinyl)methyl)-2-fluorobenzonitrile (134);

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenylsulfonyl)methyl)-2-fluorobenzonitrile (135);

4-((4-((6-(2-(2,5-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzonitrile (136);

4-((4-((6-(2-(4-chloro-2-fluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzonitrile (137);

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenylthio)methyl)benzonitrile (138);

5-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)picolinonitrile (139);

1-(5-((4-(4-cyanobenzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-yl dihydrogen phosphate (140);

5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)ethynyl)-N-(4-fluorobenzyl)thiophene-2-carboxamide (141);

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzonitrile (142);

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)-2-fluorobenzonitrile (143);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-fluorophenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-yl 2-aminoacetate hydrochloride (144);

(2S)-2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-((4-fluorophenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-yl 2,6-diaminohexanoate dihydrochloride (145);

1-(5-((4-(4-chloro-3-fluorobenzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (146);

1-(5-((4-(biphenyl-4-ylmethoxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (147);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-methylbenzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (148);

2-(2,4-difluorophenyl)-1-(5-((4-(4-ethylbenzyloxy)phenyl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (149);

1-(5-((4-(4-(difluoromethyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (150);

(+)-1-(5-((4-(4-(difluoromethyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol ((+)-150);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(4-(trifluoromethyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)propan-2-ol (151);

4-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)benzyloxy)-3-fluorobenzonitrile (152);

5-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)benzyloxy)-2-fluorobenzonitrile (153);

1-(5-((4-(4-(1H-pyrazol-1-yl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (154);

4-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)benzyloxy)benzonitrile (155);

1-(5-((4-((4-chlorophenoxy)methyl)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (156);

1-(5-((4-((biphenyl-4-yloxy)methyl)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (157);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-(oxazol-2-yl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (158);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-((4-fluorophenoxy)methyl)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (159);

1-(5-((4-((3,4-difluorophenoxy)methyl)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (160);

1-(5-((4-((4-(difluoromethyl)phenoxy)methyl)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (161);

4-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)benzylthio)benzonitrile (162);

5-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)thiophene-2-carbonitrile (163);

4-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)benzyloxy)-2-fluorobenzonitrile (164);

1-(5-((4-((4-chloro-3-fluorophenoxy)methyl)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (165);

4-((3-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzonitrile (166);

or salt thereof.

21. The method of claim 1 , wherein the compound is one of:

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl) propyl) pyridin-3-yl) ethynyl) phenoxy) methyl)-2-fluorobenzonitrile (7), or salt thereof; or

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl) propyl) pyridin-3-yl) ethynyl) phenoxy) methyl)benzonitrile (8), or salt thereof.

22. The method of claim 1 , wherein the compound is:

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl) propyl) pyridin-3-yl) ethynyl) phenoxy) methyl)-2-fluorobenzonitrile (7), or salt thereof.

23. The method of claim 1 , wherein the compound is:

4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl) propyl) pyridin-3-yl) ethynyl) phenoxy) methyl)benzonitrile (8), or salt thereof.