IP Library › Granted Patent US 10,464,922

Granted Patent B2

US 10,464,922 · App. 16/066,763 · Granted Nov 5, 2019

Metalloenzyme inhibitor compounds

Inventors: Christopher M. Yates (Raleigh, NC); Sammy R. Shaver (Chapel Hill, NC); William J. Hoekstra (Durham, NC)

Assignee: NQP 1598, Ltd.

C07D401/06 A61P35/00 C07D401/14 C07D409/14 C07D417/14 C07F9/65583

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Quick Facts

Patent No.: US 10,464,922
App. No.: 16/066,763
Granted: Nov 5, 2019
Kind: B2

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Abstract

The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

Claims (242)

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

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

R 1 is halo or alkyl;

R 2 is halo or alkyl;

or R 1 , R 2 , and the carbon atom to which they are attached form an optionally substituted cycloalkyl;

R 4 is independently aryl, heteroaryl, cycloalkyl, or arylalkyl, each substituted with 0, 1, 2 or 3 independent R 6 ;

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

each R 6 is independently optionally substituted alkyl, cyano, haloalkyl, alkoxy, halo, or haloalkoxy;

R 8 is hydrogen or halo;

M is —(CH 2 ) o — or —(C═O)—;

o is 0, 1, 2, or 3;

T is —(CH 2 ) s — or —(C═O)—;

s is 0, 1, 2, or 3;

each X and Y is independently CR 9 or N;

A and B are each hydrogen; or A, B, and the carbon to which they are attached form a carbonyl;

C and D are each hydrogen; or C, D, and the carbon to which they are attached form a carbonyl;

Ar 2 is aryl, heteroaryl, heterocycloalkyl, each independently substituted with 0, 1, 2, or 3 independent R 9 , cyano, halo, haloalkyl, NH 2 , alkoxy, haloalkoxy, optionally substituted arylalkyl,

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

each R 9 is independently optionally substituted alkyl or hydrogen; and

each R 10 is independently H, alkyl, phosphato, phosphito, alkoxyphosphato, or —C(O)alkyl optionally substituted with 1 or 2 independent NH 2 .

2. The compound of claim 1 , according to Formula (II):

or salt thereof.

3. The compound of claim 2 , according to Formula (III):

or salt thereof.

4. The compound of claim 3 , or salt thereof, wherein Ar 2 is:

wherein each R 7 is independently R 9 , cyano, halo, haloalkyl, NH 2 , alkoxy, haloalkoxy, optionally substituted arylalkyl,

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

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

each R 9 is independently optionally substituted alkyl or hydrogen; and

each R 10 is independently H, alkyl, phosphato, phosphito, alkoxyphosphato, or —C(O)alkyl optionally substituted with 1 or 2 amino.

5. The compound of claim 3 , or salt thereof, wherein Ar 2 is:

6. The compound of claim 3 , or salt thereof, wherein Ar 2 is:

7. The compound of claim 3 , or salt thereof, wherein Ar 2 is:

8. The compound of claim 3 , or salt thereof, wherein Ar 2 is:

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

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

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

12. The compound of claim 1 , or salt thereof, wherein R 4 is phenyl optionally substituted with 0, 1, 2 or 3 independent R 6 .

13. The compound of claim 1 , or salt thereof, wherein R 4 is phenyl optionally substituted with 0, 1, 2 or 3 independent halo.

14. The compound of claim 1 , or salt thereof, wherein R 4 is phenyl optionally substituted with 0, 1, 2 or 3 independent fluoro.

15. The compound of claim 1 , or salt thereof, wherein R 4 is:

16. The compound of claim 1 , or salt thereof, wherein R 4 is

17. The compound of claim 1 , or salt thereof, wherein R 4 is

18. The compound of claim 1 , or salt thereof, wherein R 4 is

19. The compound of claim 1 , or salt thereof, wherein X is N and Y is CH.

20. The compound of claim 1 , or salt thereof, wherein X is CH and Y is N.

21. The compound of claim 1 , or salt thereof, wherein both X and Y are N.

22. The compound of claim 1 , or salt thereof, wherein R 1 is fluoro; R 2 is fluoro; R 4 is

R 5 is hydrogen; and MBG is 1-tetrazolyl.

23. The compound of claim 1 , or salt thereof, wherein R 1 is fluoro; R 2 is fluoro; R 4 is

R 5 is hydrogen; X and Y are N; and MBG is 1-tetrazolyl.

24. The compound of claim 1 , or salt thereof, wherein R 1 is fluoro; R 2 is fluoro; R 4 is

R 5 is hydrogen; and MBG is 1-tetrazolyl.

25. The compound of claim 1 , or salt thereof, wherein R 1 is fluoro; R 2 is fluoro; R 4 is

R 5 is hydrogen; X and Y are N; and MBG is 1-tetrazolyl.

26. The compound of claim 1 , or salt thereof, wherein R 1 is fluoro; R 2 is fluoro; R 4 is

R 5 is hydrogen; and MBG is 1-tetrazolyl.

27. The compound of claim 1 , or salt thereof, wherein R 1 is fluoro; R 2 is fluoro; R 4 is

R 5 is hydrogen; X and Y are N; and MBG is 1-tetrazolyl.

28. The compound of claim 1 , wherein the compound is:

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

(R)-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(4-(4-fluorophenyl)piperazin-1-yl)phenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (2);

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

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

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

(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (6);

(R)-5-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)picolinonitrile (7);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)-2-fluorobenzonitrile (8);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-3-fluorobenzonitrile (9);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)benzonitrile (10);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)-3-fluorobenzonitrile (11);

(R)-6-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)nicotinonitrile (12);

1-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-3,3,3-trifluoropropan-1-ol (13);

(R)-1-(5-(4-(4-(4-aminophenyl)piperazin-1-yl)phenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (14);

(−)-2-(2,5-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(4-(2,2,2-trifluoro-1-hydroxyethyl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (15(−));

(+)-2-(2,5-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(4-(2,2,2-trifluoro-1-hydroxyethyl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (15(+));

(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(4H-1,2,4-triazol-4-yl)-1-(5-(4-(4-(4-(2,2,2-trifluoro-1-hydroxyethyl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (16);

(R)-4-((4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)methyl)benzonitrile (17);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)benzyl)piperazin-1-yl)benzonitrile (18);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)benzoyl)piperazin-1-yl)benzonitrile (19);

4-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (20);

1-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-3-((2S,3S)-2-hydroxypentan-3-yl)urea (21);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperidin-1-yl)benzonitrile (22);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazine-1-carbonyl)benzonitrile (23);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)-3-oxopiperazin-1-yl)benzonitrile (24);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)-2-oxopiperazin-1-yl)benzonitrile (25);

(R)-4-(1-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperidin-4-yl)benzonitrile (26);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)benzyl)-3-oxopiperazin-1-yl)benzonitrile (27);

(R)-4-((4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)-2-oxopiperazin-1-yl)methyl)benzonitrile (28);

(R)-4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)benzaldehyde (29);

(R)-2-(2,4-difluorophenyl)-1-(5-(4-(4-(4-((dimethylamino)methyl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (30);

1-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-2,2,2-trifluoroethyl dihydrogen phosphate (31);

(R)-5-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)picolinaldehyde (32);

(R)-2-(2,4-difluorophenyl)-1-(5-(4-(4-(6-((dimethylamino)methyl)pyridin-3-yl)piperazin-1-yl)phenyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (33);

(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(5-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-2-yl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (34);

(R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (35);

4-(4-(4-(6-(2-cyclopropyl-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)benzonitrile (36);

4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)-1-(2-hydroxypentan-3-yl)pyridin-2(1H)-one (37);

4-(4-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (38);

(−)-4-(4-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (38(−));

(+)-4-(4-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (38(+));

1-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)propan-1-ol (39);

1-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-2-methylpropan-1-ol (40);

1-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-3-methylbutan-1-ol (41);

(2R)-1-(5-(4-(4-(4-(cyclopropyl(hydroxy)methyl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (42);

1-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-2,2-dimethylpropan-1-ol (43);

(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(4-(6-(1-hydroxyethyl)pyridin-3-yl)piperazin-1-yl)phenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (44);

1-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-2-methylpropan-1-ol (45);

(2R)-1-(5-(4-(4-(6-(cyclopropyl(hydroxy)methyl)pyridin-3-yl)piperazin-1-yl)phenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (46);

(R)-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(4-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)piperazin-1-yl)phenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (47);

1-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)propan-1-ol (48);

1-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-3-methylbutan-1-ol (49);

1-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-2,2-dimethylpropan-1-ol (50);

1-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyrimidin-2-yl)-3,3,3-trifluoropropan-1-ol (51);

(R)-4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-isopropyl-1H-1,2,4-triazol-5(4H)-one (52);

(R)-4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-methyl-1H-1,2,4-triazol-5(4H)-one (53);

(R)-4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-ethyl-1H-1,2,4-triazol-5(4H)-one (54);

1-(sec-butyl)-4-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1H-1,2,4-triazol-5(4H)-one (55);

(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(4-(4-(1-hydroxyethyl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (56);

4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)-N-((2S,3S)-2-hydroxypentan-3-yl)benzamide (57);

(R)-4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5(4H)-one (58);

1-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-2-methylbutan-1-ol (59);

(R)-4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1H-1,2,4-triazol-5 (4H)-one (60);

(R)-4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-(2-(dimethylamino)ethyl)-1H-1,2,4-triazol-5(4H)-one (61);

(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(5-(2,2,2-trifluoro-1-hydroxyethyl)thiophen-2-yl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (62);

(+)-4-(4-(4-(4-(6-(1,1-difluoro-2-(4-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (63(+));

(+)-4-(4-(4-(4-(6-(1,1-difluoro-2-(3-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (64(+));

1-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-2-methylbutan-1-ol (65);

(R)-4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-(pentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (66);

(R)-4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-(2-hydroxy-2-methylpropyl)-1H-1,2,4-triazol-5(4H)-one (67);

1-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-2,3-dimethylbutan-1-ol (68);

(R)-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(4-(2-isopropyl-1H-benzo[d]imidazol-6-yl)piperazin-1-yl)phenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (69);

1-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)-3-fluoropyridin-2-yl)-3,3,3-trifluoropropan-1-ol (70);

3-(6-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)-1H-benzo[d]imidazol-2-yl)pentan-2-ol (71);

(R)-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(4-(4-(2-hydroxypropan-2-yl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (72);

(R)-2-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)benzo[d]thiazole-6-carbonitrile (73);

(R)-2-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)-1H-benzo[d]imidazole-6-carbonitrile (74);

4-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-(3-hydroxybutan-2-yl)-1H-1,2,4-triazol-5(4H)-one (75);

(R)-2-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)benzo[d]thiazole-5-carbonitrile (76);

(R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(2-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-6-yl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (77);

(R)-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(4-(2-isobutyl-1H-benzo[d]imidazol-6-yl)piperazin-1-yl)phenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (78);

(R)-2-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)-1-methyl-1H-benzo[d]imidazole-6-carbonitrile (79);

(R)-2-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)-1-methyl-1H-benzo[d]imidazole-5-carbonitrile (80);

(R)-4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-neopentyl-1H-1,2,4-triazol-5(4H)-one (81);

4-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (82);

4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)-N-((2S,3S)-2-hydroxypentan-3-yl)-N-methylbenzamide (83);

(+)-4-(4-(4-(4-(6-(1,1-difluoro-2-(3-fluorophenyl)-2-hydroxy-3-(3-methyl-1H-1,2,4-triazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (84(+));

(+)-4-(4-(4-(4-(6-(1,1-difluoro-2-(3-fluorophenyl)-2-hydroxy-3-(5-methyl-1H-1,2,4-triazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (85(+));

(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(3-(2,2,2-trifluoro-1-hydroxyethyl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (86);

(R)-4-(5-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5(4H)-one (87);

2-amino-N-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-4,4,4-trifluorobutanamide (88);

N-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-2-ethyl-3-hydroxybutanamide (89);

(R)-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(4-(2-neopentyl-1H-benzo[d]imidazol-6-yl)piperazin-1-yl)phenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (90);

(R)-1-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-3-isopropyl-1H-imidazol-2(3H)-one (91);

(2S,3S)-3-(3-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1H-1,2,4-triazol-1-yl)pentan-2-ol (92);

4-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-(2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (93);

(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(4-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-1,2,3-triazol-1-yl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (94);

(2S,3S)-3-(4-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1H-1,2,3-triazol-1-yl)pentan-2-ol (95);

(R)-1-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-3-(2,2,2-trifluoroethyl)-1H-imidazol-2(3H)-one (96);

1-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-3-(2-hydroxypentan-3-yl)-1H-imidazol-2(3H)-one (97);

(R)-1-(5-(4-(4-(1-benzyl-1H-benzo[d]imidazol-6-yl)piperazin-1-yl)phenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (98);

(2R)-1-(5-(4-(4-(6-(1,1-difluoro-2-hydroxypropyl)pyridin-3-yl)piperazin-1-yl)phenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (99);

(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(4-(3-fluoro-5-(2,2,2-trifluoro-1-hydroxyethyl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (100);

4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-pyrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (101);

(−)-4-(5-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (102(−));

(+)-4-(5-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (102(+));

4-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-(2-hydroxy-4-methylpentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (103);

(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4-yl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (104);

N-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-4,4,4-trifluoro-2-hydroxybutanamide (105);

(+)-4-(4-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (106(+));

4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-1,2,3-triazol-2-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (107);

(−)-1,1-difluoro-2-(2-fluorophenyl)-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(4-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-1,2,3-triazol-1-yl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (108(−));

(+)-1,1-difluoro-2-(2-fluorophenyl)-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(4-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-1,2,3-triazol-1-yl)phenyl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (108(+));

(−)-4-(5-(4-(4-(6-(1,1-difluoro-2-(4-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (109(−));

(+)-4-(5-(4-(4-(6-(1,1-difluoro-2-(4-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (109(+));

(−)-1,1-difluoro-2-(2-fluorophenyl)-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(6-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-1,2,3-triazol-1-yl)pyridin-3-yl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (110(−));

(+)-1,1-difluoro-2-(2-fluorophenyl)-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(6-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-1,2,3-triazol-1-yl)pyridin-3-yl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (110(+));

(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(4-(6-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-1,2,3-triazol-1-yl)pyridin-3-yl)piperazin-1-yl)phenyl)pyridin-2-yl)propan-2-ol (111);

(2S,3S)-3-(4-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)pentan-2-yl dihydrogen phosphate (112);

(2S,3S)-3-(4-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)pentan-2-yl dihydrogen phosphate (113);

(+)-(2S,3S)-3-(4-(4-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)pentan-2-yl dihydrogen phosphate (114);

4-(4-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-5-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (115);

4-(4-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(2H-1,2,3-triazol-2-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (116);

4-(4-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-pyrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (117);

1-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-3,3-dimethylbutan-1-ol (118);

(−)-1-(5-(4-(4-(6-(1,1-difluoro-2-(3-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-3,3,3-trifluoropropan-1-ol (119(−));

(+)-1-(5-(4-(4-(6-(1,1-difluoro-2-(3-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-3,3,3-trifluoropropan-1-ol (119(+));

(−)-1-(5-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-3,3,3-trifluoropropan-1-ol (120(−));

(+)-1-(5-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-3,3,3-trifluoropropan-1-ol (120(+));

(−)-1-(5-(4-(4-(6-(1,1-difluoro-2-(4-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-3,3,3-trifluoropropan-1-ol (121(−));

(+)-1-(5-(4-(4-(6-(1,1-difluoro-2-(4-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-3,3,3-trifluoropropan-1-ol (121(+));

(−)-1-(5-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-3,3,3-trifluoropropan-1-ol (122(−));

(+)-1-(5-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-3,3,3-trifluoropropan-1-ol (122(+));

(−)-4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (123(−));

(+)-4-(4-(4-(4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (123(+));

4-(5-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)-3-fluoropyridin-2-yl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (124);

4-(4-(4-(4-(6-(2-(3-chlorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-1,2,3-triazol-2-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (125);

4-(4-(4-(4-(6-(2-(3-chlorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-pyrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (126);

4-(4-(4-(4-(6-(2-(3-chlorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (127);

(−)-4-(4-(4-(4-(6-(2-(3-chlorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (127(−));

(+)-4-(4-(4-(4-(6-(2-(3-chlorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-1H-1,2,4-triazol-5(4H)-one (127(+));

(+)-(2S,3S)-3-(4-(5-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)pentan-2-yl dihydrogen phosphate (128);

1-(1-(4-(4-(4-(6-((R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)-2,2,2-trifluoroethyl dihydrogen phosphate (129);

(2S,3S)-3-(4-(5-(4-(4-(6-(1,1-difluoro-2-(2-fluorophenyl)-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenyl)piperazin-1-yl)pyridin-2-yl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)pentan-2-yl 2-(dimethylamino)acetate (130); or salt thereof.

29. The compound of claim 1 , wherein the compound is: