Metalloenzyme inhibitor compounds

1. A compound of formula (XVI), or salt thereof, wherein:

R 1 is fluoro;

R 2 is fluoro;

each R 4 is independently aryl 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;

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

each R 35 is independently

each X is independently O or S;

each Y is independently OH, NH 2 , or NH—SO 2 —R 17 ;

each n is independently 1, 2, or 3;

each o is independently 0, 1, 2, or 3;

each p is independently 0, 1, 2, or 3;

each t is independently 0, 1, 2, or 3;

each R 14 is independently:

a) alkyl substituted with 1, 2, or 3 independent OH, haloalkoxy, optionally substituted heterocyclo, optionally substituted heteroaryl,

b) alkoxy substituted with 0, 1, 2, or 3 independent OR 17 or

c)

or

d) optionally substituted heterocyclo;

each R 32 is independently:

a) haloalkyl;

b) halo;

c) alkyl substituted with 0, 1, 2, or 3 independent OH, haloalkoxy, optionally substituted heterocyclo, optionally substituted heteroaryl,

or

d)

each R 16 is independently:

a) aralkyl substituted with 0, 1, 2, or 3 independent:

(1) cyano;

(2) halo;

(3)

(4) alkoxy;

(5) haloalkyl;

(6) haloalkoxy;

(7) optionally substituted alkyl;

(8) optionally substituted aryl;

(9) optionally substituted heteroaryl; or

(10) optionally substituted heterocyclyl;

b) OR 17 ; or

c) optionally substituted aryl;

each R 17 is independently H, optionally substituted alkyl, haloalkyl, or

each R 18 is independently:

a) aryl substituted with 0, 1, 2, or 3 independent:

(1) halo;

(2) haloalkyl;

(3) alkoxy;

(4) haloalkoxy;

(5) optionally substituted cycloalkyl;

(6) optionally substituted heterocyclyl;

(7) optionally substituted alkyl;

(8)

(9) OR 19 ;

(10) SR 19 ;

(11) optionally substituted heteroaryl; or

(12) cyano;

b) optionally substituted cycloalkyl;

c) optionally substituted heteroaryl;

d) optionally substituted heterocyclyl;

e) optionally substituted alkyl;

f) optionally substituted cycloalkylalkyl;

g) optionally substituted cycloalkylalkoxy;

h) haloalkyl;

i) haloalkoxy;

j) haloalkoxyalkyl;

k)

or

l) optionally substituted aralkyl;

each R 19 is independently H, optionally substituted alkyl, or haloalkyl;

each R 20 is independently H, optionally substituted alkyl, or

each R 33 is independently H, optionally substituted heteroaryl, optionally substituted alkyl,

optionally substituted haloalkyl, optionally substituted alkylcarbonyl, or

each R 22 is independently:

a)

b) optionally substituted alkyl;

c) optionally substituted aryl;

d) optionally substituted heteroaryl;

e) optionally substituted cycloalkyl; or

f) optionally substituted heterocyclyl; and

each R 25 is independently optionally substituted aryl; optionally substituted arylalkyl, haloalkoxy, (haloalkoxy)alkyl, cycloalkyl, alkyl, —CH 2 CF 2 CF 3 , —CF 2 CF 3 , or

2. A compound of formula (VII), or salt thereof, wherein:

R 1 is halo;

R 2 is halo;

each R 27 is independently alkyl, cycloalkyl, or aralkyl, each 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;

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

each R 30 is independently

each X is independently O or S;

each Y is independently OH, NH 2 , or NH—SO 2 —R 17 ;

each n is independently 0, 1, 2, or 3;

each o is independently 0, 1, 2, or 3;

each p is independently 0, 1, 2, or 3;

each t is independently 0, 1, 2, or 3;

each R 31 is independently:

a) alkyl substituted with 1, 2, or 3 independent OH, haloalkoxy, optionally substituted heterocyclo, optionally substituted heteroaryl,

b) alkoxy substituted with 0, 1, 2, or 3 independent OR 17 or

c)

d) halo;

e) haloalkyl;

f) haloalkoxy; or

g) optionally substituted heterocyclo;

each R 32 is independently:

a) haloalkyl;

b) halo;

c) alkyl substituted with 0, 1, 2, or 3 independent OH, haloalkoxy, optionally substituted heterocyclo, optionally substituted heteroaryl,

or

d)

or

e) haloalkoxy;

each R 16 is independently:

a) aralkyl substituted with 0, 1, 2, or 3 independent:

(1) cyano;

(2) halo;

(3)

(4) alkoxy;

(5) haloalkyl;

(6) haloalkoxy;

(7) optionally substituted alkyl;

(8) optionally substituted aryl;

(9) optionally substituted heteroaryl; or

(10) optionally substituted heterocyclyl;

b) OR 17 ; or

c) optionally substituted aryl;

each R 17 is independently H, optionally substituted alkyl, haloalkyl, or

each R 18 is independently:

a) aryl substituted with 0, 1, 2, or 3 independent:

(1) halo;

(2) haloalkyl;

(3) alkoxy;

(4) haloalkoxy;

(5) optionally substituted cycloalkyl;

(6) optionally substituted heterocyclyl;

(7) optionally substituted alkyl;

(8)

(9) OR 19 ;

(10) SR 19 ;

(11) optionally substituted heteroaryl; or

(12) cyano;

b) optionally substituted cycloalkyl;

c) optionally substituted heteroaryl;

d) optionally substituted heterocyclyl;

e) optionally substituted alkyl;

f) optionally substituted cycloalkylalkyl;

g) optionally substituted cycloalkylalkoxy;

h) haloalkyl;

i) haloalkoxy;

j) haloalkoxyalkyl;

k)

or

l) optionally substituted aralkyl;

each R 19 is independently H, optionally substituted alkyl, or haloalkyl;

each R 20 is independently H, optionally substituted alkyl, haloalkyl, or

each R 33 is independently H, optionally substituted heteroaryl, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted alkylcarbonyl, or

each R 22 is independently:

a)

b) optionally substituted alkyl;

c) optionally substituted aryl;

d) optionally substituted heteroaryl;

e) optionally substituted cycloalkyl; or

f) optionally substituted heterocyclyl; and

each R 25 is independently optionally substituted aryl; optionally substituted arylalkyl, haloalkoxy, (haloalkoxy)alkyl, cycloalkyl, alkyl, —CH 2 CF 2 CF 3 , —CF 2 CF 3 , or

3. A compound of formula (XV), or salt thereof, wherein:

each R 4 is independently aryl 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;

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

each R 36 is independently

each n is independently 1, 2, or 3;

each p is independently 0, 1, 2, or 3;

each R 37 is independently halo, haloalkyl, or haloalkoxy:

each R 38 is independently:

a) alkyl substituted with 1, 2, or 3 independent OH, haloalkoxy, optionally substituted heterocyclo, optionally substituted heteroaryl,

b) alkoxy substituted with 0, 1, 2, or 3 independent OR N or

c)

or

d) optionally substituted heterocyclo;

each R 17 is independently H, optionally substituted alkyl, haloalkyl, or

each R 19 is independently H, optionally substituted alkyl, or haloalkyl;

each R 33 is independently H, optionally substituted heteroaryl, optionally substituted alkyl,

optionally substituted haloalkyl, optionally substituted alkylcarbonyl, or

4. The compound of claim 1 , wherein R 5 is H.

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

6. The compound of claim 1 , wherein R 5 is phosphato.

7. The compound of claim 1 , wherein n is 1 and R 35 is at the 4-position of the phenyl ring within formula XVI from claim 1 .

8. The compound of claim 2 , wherein n is 1 and R 30 is at the 4-position of the phenyl ring within formula VII from claim 2 .

9. The compound of claim 3 , wherein R 36 is at the 4-position of the phenyl ring within formula XV from claim 3 .

10. The compound of claim 1 , which is one of:

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

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

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

1-(5-((4-(4-(aminomethyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-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-((5-(trifluoromethyl)thiophen-2-yl)methoxy)phenyl)ethynyl)pyridin-2-yl)propan-2-ol (5);

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

1-(5-((4-((4-chlorophenylamino)methyl)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (7);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-((4-fluorophenylamino)methyl)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (8);

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

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(4-((2,2,2-trifluoroethoxy)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)propan-2-ol (10);

2-(2,4-difluorophenyl)-1-(5-((4-(4-((dimethylamino)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (11);

N-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyl)acetamide (12);

1-(5-((4-(4-((1H-pyrazol-1-yl)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (13);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(4-((2,2,2-trifluoroethylamino)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)propan-2-ol (14);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-(2-hydroxyethoxy)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (15);

2-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)phenoxy)acetic acid (16);

4-(2-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenyl)-2-oxoethyl)-2-fluorobenzonitrile (17);

1-(5-((4-((4-(difluoromethyl)phenylamino)methyl)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (18);

2-(4-chloro-3-fluorophenyl)-1-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenyl)ethanone (19);

2-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzylamino)acetic acid (20);

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

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

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-(pyrrolidin-1-ylmethyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (23);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-((oxazol-2-ylamino)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (24);

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

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

2-(2,4-difluorophenyl)-1-(5-((4-((5-((dimethylamino)methyl)thiophen-3-yl)methoxy)phenyl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (27);

1-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenyl)-2-(4-((dimethylamino)methyl)phenyl)ethanone (28);

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

2-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyloxy)acetonitrile (30);

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

2-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzylamino)acetonitrile (32);

1-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyl)-1H-pyrazole-4-carbonitrile (33);

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

1-(5-((4-(4-((4-chloro-1H-pyrazol-1-yl)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (35);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-((4-fluoro-1H-pyrazol-1-yl)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (36);

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

N-((1-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyl)-1H-pyrazol-3-yl)methyl)acetamide (38);

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

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-((4-(1-hydroxyethyl)-1H-pyrazol-1-yl)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (40);

1-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyl)-1H-pyrazole-4-carboxylic acid (41);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-((methyl(oxazol-2-yl)amino)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (42);

2-((4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyl)(methyl)amino)acetonitrile (43);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-((methyl(2,2,2-trifluoroethyl)amino)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (44);

1-(5-((4-(4-(((2,2-difluoro-2-hydroxyethyl)(methyl)amino)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (45);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-(((2-hydroxy-2-methylpropyl)(methyl)amino)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (46);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-(((2-hydroxypropyl)(methyl)amino)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (47);

2-((4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzylamino)methyl)-1H-imidazole-1-carbaldehyde (48);

2-(((4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyl)(methyl)amino)methyl)-1H-imidazole-1-carbaldehyde (49);

1-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyl)-1H-imidazole-4-carbonitrile (50);

1-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyl)-N-methyl-1H-imidazole-2-carboxamide (51);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(4-((4-methylpiperazin-1-yl)methyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (52);

4-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyl)piperazine-1-carbaldehyde (53);

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

1-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyl)imidazolidin-2-one (55);

1-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzyl)imidazolidine-2,4-dione (56);

1-(5-((4-(4-(1-(1H-pyrazol-1-yl)ethyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (57);

4-(2-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenyl)-2-hydroxyethyl)benzonitrile (58);

4-(4-((4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)phenyl)-1-((S)-2-methylpentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (59);

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

2-(2,4-difluorophenyl)-1-(5-((4-(4-(1-(dimethylamino)-2-hydroxyethyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (61);

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

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

1-(5-((4-(3-((1H-pyrazol-1-yl)methyl)benzyloxy)phenyl)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-(5-((4-(3-(1-(dimethylamino)-2-hydroxyethyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (65);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(3-(2-hydroxy-1-(1H-pyrazol-1-yl)ethyl)benzyloxy)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (66);

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

2-(2,4-difluorophenyl)-1-(5-((4-((5-((dimethylamino)methyl)thiophen-2-yl)methoxy)phenyl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (68);

1-(5-((4-((5-((1H-pyrazol-1-yl)methyl)thiophen-2-yl)methoxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (69);

1-(5-((4-((5-(difluoromethyl)thiophen-2-yl)methoxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (73);

1-(5-((4-((5-chlorothiophen-2-yl)methoxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (74);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-((4-chlorophenyl)(hydroxy)methyl)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (79);

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

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((4-(1-hydroxy-2-(2,2,2-trifluoroethoxy)ethyl)phenyl)ethynyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (81);

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

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

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

1-(4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenyl)-3-(dimethylamino)-2,2-difluoropropan-1-ol (85);

1-(5-((4-(cyclopropyl(hydroxy)methyl)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (86); or a salt thereof.

11. The compound of claim 2 , which is one of:

4-((4-((6-(2-((1H-tetrazol-1-yl)methyl)-1,1-difluoro-2-hydroxy-3-methylbutyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzonitrile (70);

4-((4-((6-(2-((1H-tetrazol-1-yl)methyl)-1,1-difluoro-2-hydroxy-3,3-dimethylbutyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzonitrile (71);

4-((4-((6-(2-cyclopropyl-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)ethynyl)phenoxy)methyl)benzonitrile (72); or a salt thereof.

12. The compound of claim 3 , which is one of:

2-(2,4-difluorophenyl)-1-(5-((4-(4-((dimethylamino)methyl)-3-fluorobenzyloxy)phenyl)ethynyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (75);

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

1-(5-((4-(4-((1H-pyrazol-1-yl)methyl)-3-fluorobenzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (77);

1-(5-((4-(4-((4-chloro-1H-pyrazol-1-yl)methyl)-3-fluorobenzyloxy)phenyl)ethynyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (78); or a salt thereof.

13. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

14. The composition of claim 13 further comprising a therapeutic agent in addition to the compound of formula (XVI).

15. The composition of claim 13 further comprising a therapeutic agent in addition to the compound of formula (XVI) wherein said therapeutic agent is an anti-cancer agent, antifungal agent, cardiovascular agent, anti-inflammatory agent, chemotherapeutic agent, an anti-angiogenesis agent, cytotoxic agent, an anti-proliferation agent, metabolic disease agent, ophthalmologic disease agent, central nervous system (CNS) disease agent, urologic disease agent, or gastrointestinal disease agent.

16. A method of inhibiting metalloenzyme activity comprising contacting a compound of claim 1 with a metalloenzyme.

17. The method of claim 16 , wherein the contacting is in vivo.

18. The method of claim 16 , wherein the contacting is in vitro.

19. A method of treating a subject suffering from a metalloenzyme-related disorder or disease, comprising administering to the subject an effective amount of a compound of claim 1 .