Metalloenzyme inhibitor compounds

1. A method of inhibiting metalloenzyme activity comprising contacting a compound of Formula I, or salt thereof, with a metalloenzyme:

MBG is optionally substituted tetrazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;

R 1 is halo or haloalkyl;

R 2 is H, halo, alkyl, or haloalkyl;

R 3 is independently H, alkyl, alkenyl, cycloalkyl, heteroaryl, hydroxyalkyl, cyano, haloalkyl, halo, —C(O)phenyl, —CH(OH)(aryl), —CH 2 (aryl), —CH 2 (heteroaryl), —CF 2 (aryl), —CF 2 (heteroaryl), —CH 2 O(aryl), —CH 2 O(heteroaryl), —CH 2 S(O) x (aryl), and cyclic amino, wherein each of the alkyl, alkenyl, cycloalkyl, heteroaryl, hydroxyalkyl, haloalkyl, —C(O)phenyl, —CH(OH)(aryl), —CH 2 (aryl), —CH 2 (heteroaryl), —CF 2 (aryl), CF 2 (heteroaryl), —CH 2 O(aryl), —CH 2 O(heteroaryl), —CH 2 S(O) x (aryl), and cyclic amino may be optionally substituted with 1, 2 or 3 independent R 7 ;

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

R 5 is independently H, halo, alkyl, alkoxy, cyano, haloalkyl, haloalkoxy, halothioalkyl, thioalkyl, SF 3 , SF 6 , SCN, SO 2 R 11 , cycloalkyl, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl;

R 6 is independently H, halo, alkyl, alkoxy, cyano, haloalkyl, haloalkoxy, halothioalkyl, thioalkyl, SF 3 , SF 6 , SCN, SO 2 R 11 , cycloalkyl, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl;

each R 7 is independently cyano, cycloalkyl, haloalkyl, hydroxy, alkoxy, aryl, aryloxy, heteroaryloxy, halo, haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl;

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

R 9 is H, halo, or haloalkyl;

R 10 is H, alkyl, —Si(R 12 ) 3 , —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or C(O)alkyl optionally substituted with amino;

R 11 is independently alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

R 12 is independently alkyl or aryl; and

x is independently 0, 1, or 2.

2. The method of claim 1 , wherein the metalloenzyme is lanosterol demethylase (CYP51).

3. A method of treating a subject suffering from or susceptible to a metalloenzyme-related disorder or disease, wherein the subject has been identified as in need of treatment for a metalloenzyme-related disorder or disease, comprising administering to said subject in need thereof, an effective amount of a compound of Formula I, or salt thereof, such that said subject is treated for said disorder:

MBG is optionally substituted tetrazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;

R 1 is halo or haloalkyl;

R 2 is H, halo, alkyl, or haloalkyl;

R 3 is independently H, alkyl, alkenyl, cycloalkyl, heteroaryl, hydroxyalkyl, cyano, haloalkyl, halo, —C(O)phenyl, —CH(OH)(aryl), —CH 2 (aryl), —CH 2 (heteroaryl), —CF 2 (aryl), —CF 2 (heteroaryl), —CH 2 O(aryl), —CH 2 O(heteroaryl), —CH 2 S(O) x (aryl), and cyclic amino, wherein each of the alkyl, alkenyl, cycloalkyl, heteroaryl, hydroxyalkyl, haloalkyl, —C(O)phenyl, —CH(OH)(aryl), —CH 2 (aryl), —CH 2 (heteroaryl), —CF 2 (aryl), CF 2 (heteroaryl), —CH 2 O(aryl), —CH 2 O(heteroaryl), —CH 2 S(O) x (aryl), and cyclic amino may be optionally substituted with 1, 2 or 3 independent R 7 ;

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

R 5 is independently H, halo, alkyl, alkoxy, cyano, haloalkyl, haloalkoxy, halothioalkyl, thioalkyl, SF 3 , SF 6 , SCN, SO 2 R 11 , cycloalkyl, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl;

R 6 is independently H, halo, alkyl, alkoxy, cyano, haloalkyl, haloalkoxy, halothioalkyl, thioalkyl, SF 3 , SF 6 , SCN, SO 2 R ii , cycloalkyl, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl;

each R 7 is independently cyano, cycloalkyl, haloalkyl, hydroxy, alkoxy, aryl, aryloxy, heteroaryloxy, halo, haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl;

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

R 9 is H, halo, or haloalkyl;

R 10 is H, alkyl, —Si(R 12 ) 3 , —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)alkyl optionally substituted with amino;

R 11 is independently alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

R 12 is independently alkyl or aryl; and

x is independently 0, 1, or 2.

4. The method of claim 3 , wherein the disease or disorder is mediated by any of 4-hydroxyphenyl pyruvate dioxygenase, 5-lipoxygenase, adenosine deaminase, alcohol dehydrogenase, aminopeptidase N, angiotensin converting enzyme, aromatase (CYP19), calcineurin, carbamoyl phosphate synthetase, carbonic anhydrase family, catechol-O-methyl transferase, cyclooxygenase family, dihydropyrimidine dehydrogenase-1, DNA polymerase, farnesyl diphosphate synthase, farnesyl transferase, fumarate reductase, GABA aminotransferase, HIF-prolyl hydroxylase, histone deacetylase family, HIV integrase, HIV-1 reverse transcriptase, isoleucine tRNA ligase, lanosterol demethylase (CYP51), matrix metalloprotease family, methionine aminopeptidase, neutral endopeptidase, nitric oxide synthase family, phosphodiesterase III, phosphodiesterase IV, phosphodiesterase V, pyruvate ferredoxin oxidoreductase, renal peptidase, ribonucleoside diphosphate reductase, thromboxane synthase (CYP5a), thyroid peroxidase, tyrosinase, urease, or xanthine oxidase.

5. The method of claim 3 , wherein the disease or disorder is cancer, cardiovascular disease, endocrinologic disease, inflammatory disease, infectious disease, gynecologic disease, metabolic disease, ophthalmologic disease, central nervous system (CNS) disease, urologic disease, or gastrointestinal disease.

6. The method of claim 3 , wherein the disease or disorder is systemic fungal infection, or onychomycosis.

7. The method of claim 3 , wherein R 1 is fluoro.

8. The method of claim 3 , wherein R 2 is fluoro.

9. The method of claim 3 , wherein R 1 and R 2 are fluoro.

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

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

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

13. The method of claim 3 , wherein R 4 is 2,4-difluorophenyl.

14. The method of claim 3 , wherein R 5 is halo.

15. The method of claim 3 , wherein R 3 is heteroaryl optionally substituted with 1, 2 or 3 independent R 7 .

16. The method of claim 3 , wherein:

R 1 is fluoro;

R 2 is fluoro;

R 4 is 2,4-difluorophenyl; and

R 3 is alkyl substituted with 1, 2 or 3 independent R 7 .

17. The method of claim 3 , wherein:

R 1 is fluoro;

R 2 is fluoro;

R 4 is 2,4-difluorophenyl; and

R 3 is alkenyl substituted with 1, 2 or 3 independent R 7 .

18. The method of claim 3 , wherein:

R 3 is halo.

19. The method of claim 3 , wherein the compound is one of:

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

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

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

(E)-Ethyl 3-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)acrylate (4);

Ethyl 3-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)propanoate (5);

(E)-2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(3-(2,2,2-trifluoroethoxy)prop-1-enyl)pyridin-2-yl)propan-2-ol (6);

(E)-4-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)but-3-en-2-one (7);

4-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)butan-2-one (8);

1-(5-(2H-1,2,3-Triazol-2-yl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (9);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-fluoropyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (10);

2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-1-(pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (11);

1-(5-Chloropyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (12);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(4-fluoropyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (13);

1-(4-Chloropyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (14);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(5-fluoropyrimidin-4-yl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (15);

2-(2,5-Difluorophenyl)-1,1-difluoro-1-(4-fluoropyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (16);

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

1-(5-Cyclopropylpyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (18);

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

1-(6-Bromopyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (20);

1-(5-Bromopyridin-2-yl)-2-(2,5-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (21);

1-(5-Bromopyridin-2-yl)-2-(4-chloro-2-fluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (22);

1-(5-Bromopyridin-2-yl)-1,1-difluoro-2-(2-fluoro-4-(trifluoromethyl)phenyl)-3-(1H-tetrazol-1-yl)propan-2-ol (23);

1-(4-Bromopyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (24);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-methylpyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (25);

2-(4-Chloro-2-fluorophenyl)-1-(5-chloropyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (26);

2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-1-(5-fluoropyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (27);

1-(5-(2H-1,2,3-Triazol-2-yl)pyridin-2-yl)-2-(4-chloro-2-fluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (28);

1-(6′-Chloro-[3,3′-bipyridin]-6-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (30);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(6′-fluoro-[3,3′-bipyridin]-6-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (31);

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

1-(5-(5-(Difluoromethyl)thiophen-2-yl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (33);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(5-(trifluoromethyl)thiophen-2-yl)pyridin-2-yl)propan-2-ol (34);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(6′-(trifluoromethyl)-[3,3′-bipyridin]-6-yl)propan-2-ol (35);

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

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

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(thiazol-2-yl)pyridin-2-yl)propan-2-ol (38);

2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(2,2,2-trifluoroethyl)pyridin-2-yl)propan-2-ol (39);

2-(4-Chloro-2-fluorophenyl)-1-(5-cyclopropylpyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (40);

Methyl 2-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)thio)acetate (41);

(E)-1-(5-(3-(1H-Tetrazol-1-yl)prop-1-en-1-yl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (42);

(E)-3-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)prop-2-en-1-ol (43);

3-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)propan-1-ol (44);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(3-(2,2,2-trifluoroethoxy)propyl)pyridin-2-yl)propan-2-ol (45);

(E)-4-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)but-3-en-2-ol (46);

4-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)butan-2-ol (47);

(E)-2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(3-methoxyprop-1-en-1-yl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (48);

(Z)-2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(3-methoxyprop-1-en-1-yl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (49);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(3-methoxypropyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (50);

(E)-2-(2,4-Difluorophenyl)-1-(5-(3-ethoxyprop-1-en-1-yl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (51);

(Z)-2-(2,4-Difluorophenyl)-1-(5-(3-ethoxyprop-1-en-1-yl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (52);

2-(2,4-Difluorophenyl)-1-(5-(3-ethoxypropyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (53);

(E)-2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(3-isopropoxyprop-1-en-1-yl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (54);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(3-isopropoxypropyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (55);

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

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-2-yl)propan-2-ol (57);

2-(5-Bromopyridin-2-yl)-1-(2,4-difluorophenyl)-2,2-difluoro-1-(pyrimidin-5-yl)ethanol (58);

1-(5-(Cyclopropylmethyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (59);

2-(4-Chloro-2-fluorophenyl)-1-(5-(cyclopropylmethyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (60);

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

1-(5-Bromopyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-pyrazol-3-yl)propan-2-ol (62);

1-(5-(2H-1,2,3-Triazol-2-yl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-pyrazol-3-yl)propan-2-ol (63);

1-(5-(1H-1,2,3-Triazol-1-yl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-pyrazol-3-yl)propan-2-ol (64);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-pyrazol-4-yl)-1-(pyridin-2-yl)propan-2-ol (65);

(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)(4-(trifluoromethyl)phenyl)methanone (66);

(4-Chlorophenyl)(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)methanone (67);

(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)(4-(2,2,2-trifluoroethoxy)phenyl)methanone (68);

(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)(4-fluorophenyl)methanone (69);

(3,4-Difluorophenyl)(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)methanone (70);

(4-Chloro-3-fluorophenyl)(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)methanone (71);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(hydroxy(4-(trifluoromethyl)phenyl)methyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (72);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(trifluoromethyl)benzyl)pyridin-2-yl)propan-2-ol (73);

1-(5-((4-Chlorophenyl)difluoromethyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (74);

1-(5-Benzylpyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (75);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(trifluoromethoxy)benzyl)pyridin-2-yl)propan-2-ol (76);

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

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

4-((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)methoxy)benzonitrile (79);

4-((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)methoxy)benzonitrile (80);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-morpholinopyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (81);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(piperidin-1-yl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (82);

1-(5-Bromopyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(oxazol-5-yl)propan-2-ol (83);

3-(5-Bromopyridin-2-yl)-2-(2,4-difluorophenyl)-3-fluoro-1-(1H-tetrazol-1-yl)butan-2-ol (84);

3-(5-Bromopyridin-2-yl)-2-(2,4-difluorophenyl)-3-fluoro-1-(1H-tetrazol-1-yl)butan-2-ol (85);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(pyridin-2-yl)-3-(thiazol-5-yl)propan-2-ol (86);

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

4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)methoxy)-3-fluorobenzonitrile (88);

3-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)methoxy)-2-fluorobenzonitrile (89);

4-(((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)methyl)thio)-3-fluorobenzonitrile (90);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(isopropoxymethyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (91);

1-(5-((difluoromethoxy)methyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (92);

1-(5-chloro-[2,3′-bipyridin]-6′-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (93);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(trifluoromethyl)-[2,3′-bipyridin]-6′-yl)propan-2-ol (94);

6′-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)-[2,3′-bipyridine]-5-carbonitrile (95);

1-([3,4′-bipyridin]-6-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (96);

1-(5-((6-chloropyridin-3-yl)methyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (97);

6-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)methoxy)nicotinonitrile (98);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(((5-(trifluoromethyl)pyridin-2-yl)oxy)methyl)pyridin-2-yl)propan-2-ol (99);

1-(5-(((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)methyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (100);

1-(5-(difluoro(4-fluorophenyl)methyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (101);

1-(5-(difluoro(4-(trifluoromethyl)phenyl)methyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (102); or

4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)difluoromethyl)benzonitrile (103).

20. The method of claim 3 , wherein the disease or disorder is systemic fungal infection, skin structure fungal infection, mucosal fungal infection, or onychomycosis.