Metalloenzyme inhibitor compounds

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

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 1,1′-biphenyl substituted with 4′-OCH 2 CF 3 or 4′-F, or heteroaryl, which may be optionally substituted with 1, 2 or 3 independent R 5 ;

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

each R 5 is independently H, halo, aryl optionally substituted with 1, 2 or 3 independent R 6 , heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alkylaryl, arylalkynyl, arylalkyl, cycloalkyl, halocycloalkyl, thioalkyl, SF 3 , SF 6 , SCN, SO 2 R 7 , C(O)alkyl, C(O)OH, C(O)Oalkyl;

each R 6 is independently alkyl, thioalkyl, cyano, haloalkyl, hydroxy, alkoxy, halo, haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)Oalkyl, SF 3 , SF 6 , SCN, SO 3 H; and SO 2 R 7 ;

R 7 is independently alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

R 8 is H, —Si(R 9 ) 3 , —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)alkyl optionally substituted with amino;

R 9 is independently alkyl or aryl;

and wherein R 3 is not optionally substituted monocyclic pyridyl.

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

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

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

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

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

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

8. The compound of claim 1 , wherein R 4 is 2,4-difluorophenyl.

9. The compound of claim 1 , wherein R 5 is halo.

10. The compound of claim 1 , wherein R 3 is heteroaryl optionally substituted with 1, 2 or 3 independent R 5 ; wherein at least one R 5 is halo.

11. The compound of claim 1 , wherein:

R 1 is fluoro;

R 2 is fluoro;

R 4 is 2,4-difluorophenyl; and

R 3 is heteroaryl other than pyridyl, substituted with 1, 2 or 3 independent R 5 .

12. The compound of claim 1 , wherein:

R 1 is fluoro;

R 2 is fluoro;

R 4 is 2,4-difluorophenyl; and

R 3 is bicyclic heteroaryl substituted with 1, 2 or 3 independent R 5 .

13. The compound of claim 1 , wherein:

R 3 is 2-quinolinyl substituted with 1, 2 or 3 independent R 5 .

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

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

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

4-(2-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)thiazol-4-yl)benzonitrile (3);

1-(6-Chloroquinolin-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-1-(quinolin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (5);

1-(Benzo[d]thiazol-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (6);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(pyrimidin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (7);

2-(4-Chloro-2-fluorophenyl)-1-(6-chloroquinolin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (8);

1-(6-Bromoquinolin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (9);

1-(6-Chloroquinoxalin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (10);

1-(6-Chlorobenzo[d]thiazol-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (11);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(thiazol-2-yl)propan-2-ol (12);

1-(5-Bromothiophen-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-(thiophen-2-yl)propan-2-ol (14);

1-(6-Chloroquinolin-2-yl)-1,1-difluoro-2-(4-methoxyphenyl)-3-(1H-tetrazol-1-yl)propan-2-ol (15);

1-(6-Chloroquinolin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(2H-tetrazol-2-yl)propan-2-ol (16);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(6-fluoroquinolin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (17);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(6-(trifluoromethyl)quinolin-2-yl)propan-2-ol (18);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(6-(2,2,2-trifluoroethoxy)quinolin-2-yl)propan-2-ol (19);

1-(6-Chloroquinolin-2-yl)-1,1-difluoro-2-(2-fluoro-4-(trifluoromethyl)phenyl)-3-(1H-tetrazol-1-yl)propan-2-ol (20);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(6-(trifluoromethoxy)quinolin-2-yl)propan-2-ol (21);

2-(2-Chloro-4-(trifluoromethyl)phenyl)-1-(6-chloroquinolin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (22);

1-(6-Chloroquinolin-2-yl)-2-(3,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (23);

2-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)quinoline-6-carbonitrile (24);

1-(6-(Difluoromethyl)quinolin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (25);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(6-methylquinolin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (26);

1-(6-Bromobenzo[d]thiazol-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (27);

1-(6-Chloroquinolin-2-yl)-2-(2,5-difluorophenyl)-1,1-difluoro-3-(2H-tetrazol-2-yl)propan-2-ol (28);

1-(5,6-Dichloroquinolin-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-(2,2,2-trifluoroethoxy)quinolin-2-yl)propan-2-ol (30);

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

1-(6-Chloroquinolin-2-yl)-1,1-difluoro-2-(4-fluorophenyl)-3-(1H-tetrazol-1-yl)propan-2-ol (32);

2-(4-Chloro-2-fluorophenyl)-1-(6-chloroquinoxalin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (34);

1-(7-Chloroisoquinolin-3-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (37);

1-(6-Bromoquinoxalin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (38);

1-(5-(4-(Difluoromethoxy)phenyl)pyrazin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (39);

1-(5-(4-Chlorophenyl)pyrazin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (40);

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

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(trifluoromethoxy)phenyl)pyrazin-2-yl)propan-2-ol (42);

1-(5-(4-Bromophenyl)pyrazin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (43);

2-(2,4-Difluorophenyl)-1-(5-(3,4-difluorophenyl)pyrazin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (44);

1,1-Difluoro-2-(4-fluorophenyl)-3-(1H-tetrazol-1-yl)-1-(5-(4-(trifluoromethoxy)phenyl)pyrazin-2-yl)propan-2-ol (45);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(4-fluorophenyl)pyrazin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (46);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(4-fluorophenyl)pyrazin-2-yl)-3-(2H-tetrazol-2-yl)propan-2-ol (47);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(4-methoxyphenyl)pyrazin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (48);

1-(5-Chloropyrazin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (49);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-((4-fluorophenyl)ethynyl)pyrazin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (50);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-((4-fluorophenyl)ethynyl)pyrazin-2-yl)-3-(2H-tetrazol-2-yl)propan-2-ol (51);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(4-fluorophenethyl)pyrazin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (52);

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

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(6-(trifluoromethoxy)quinoxalin-2-yl)propan-2-ol (54);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(6-fluoroquinoxalin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (55);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(6-(4-(trifluoromethyl)phenyl)pyridazin-3-yl)propan-2-ol (56);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(6-(4-(trifluoromethoxy)phenyl)pyridazin-3-yl)propan-2-ol (57);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(6-(4-fluorophenyl)pyridazin-3-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (58);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(6-vinylquinoxalin-2-yl)propan-2-ol (59);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(4′-(2,2,2-trifluoroethoxy)-[1,1′-biphenyl]-4-yl)propan-2-ol (60); or

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(4′-fluoro-[1,1′-biphenyl]-4-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (61).

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