Metalloenzyme inhibitor compounds
The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.
1. A method of treating a metalloenzyme-mediated disease or disorder in or on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
R 1 is H, halo, alkyl or haloalkyl;
R 2 is H, halo, alkyl or haloalkyl;
R 3 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 1, 2 or 3 independent R 6 , heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, 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, hydroxyl, 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;
wherein R 3 is not optionally substituted monocyclic pyridyl optionally substituted with 1, 2 or 3 independent R 5 ; and
the metalloenzyme-related disorder or disease is mediated by lanosterol demethylase (CYP51).
2. A method of inhibiting metalloenzyme activity in a microorganism on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
R 1 is H, halo, alkyl 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, 2or 3 independent R 6 ;
each R 5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R 6 , heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, 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, hydroxyl, 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;
wherein R 3 is not optionally substituted monocyclic pyridyl optionally substituted with 1, 2or 3 independent R 5 ; and
wherein the metalloenzyme is lanosterol demethylase (CYP51).
3. A method of treating a fungal disease or disorder in or on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
R 1 is H, halo, alkyl 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, 2or 3 independent R 6 ;
each R 5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R 6 , heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, 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, hydroxyl, 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 optionally substituted with 1, 2or 3 independent R 5 .
4. A method of treating fungal growth in or on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
R 1 is H, halo, alkyl 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, 2or 3 independent R 6 ;
each R 5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R 6 , heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, 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, hydroxyl, 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 optionally substituted with 1, 2 or 3 independent R 5 .
5. A method of inhibiting microorganisms in or on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
R 1 is H, halo, alkyl 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 1, 2 or 3 independent R 6 , heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, 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, hydroxyl, 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 optionally substituted with 1, 2 or 3 independent R 5 ; and
wherein the microorganism belongs to at least one genera selected from Blumeria, Podospaera, Sphaerotheca, Unicinula, Erysiphe, Puccinia, Phakopspora, Gymnosporangium, Hemileia, Uromyces, Alternia, Cercospora, Cladosporium, Cochliobolus, Colletotrichum, Magnaporthe, Mycosphaerella, Phaeosphaeria, Pyrenophora, Ramularia, Rhyncosporium, Septoria, Venturia, Ustilago, Aspergillus, Penicillium, Drechslera, Fusarium, Botrytis, Gibberella, Rhizoctonia, Pseudocercosporella, Sclerotinia, Helminithosporium, Stagonospora, Exserohilum, and Pyricularia.
6. A composition comprising a compound of Formula I or salt thereof, wherein:
MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
R 1 is H, halo, alkyl 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 1, 2 or 3 independent R 6 , heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, 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, hydroxyl, 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 optionally substituted with 1, 2 or 3 independent R 5 , said composition further comprising an azole fungicide selected from epoxiconazole, tebuconazole, fluquinconazole, flutriafol, metaconazole, myclobutanil, cycproconazole, prothioconazole and propiconazole.
7. A composition comprising a compound of Formula I, or salt thereof, wherein:
MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
R 1 is H, halo, alkyl 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, 2or 3 independent R 6 ;
each R 5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R 6 , heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, 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, hydroxyl, 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 optionally substituted with 1, 2 or 3 independent R 5 , said composition further comprising a strobilurin fungicide from the group trifloxystrobin, pyraclostrobin, orysastrobin, fluoxastrobin and azoxystrobin.
8. A method of inhibiting microorganisms in or on a plant comprising contacting a compound of Formula I with the plant or seeds, wherein:
MBG is optionally substituted tetrazoyl, optionally substituted triazolyl, optionally substituted oxazolyl, optionally substituted pyrimidinyl, optionally substituted thiazolyl, or optionally substituted pyrazolyl;
R 1 is H, halo, alkyl 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, 2or 3 independent R 6 ;
each R 5 is independently H, halo, aryl optionally substituted 1, 2 or 3 independent R 6 , heteroaryl, haloalkyl, haloalkoxy, cyano, nitro, alkyl, alkoxy, alkenyl, haloalkenyl, arylalkenyl, alkynyl, haloalkynyl, alklaryl, arylalkynyl, arylalkyl, cycloalklyl, 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, hydroxyl, 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 optionally substituted with 1, 2 or 3 independent R 5 ; and
wherein the microorganism is selected from the group consisting of Venturia inaequalis, Septoria tritici, Cercospora beticola, Cercospora arachidicola, Colletotrichum lagenarium, Puccinia graminis f. sp. tritici, Puccinia recondite tritici, Uncinula necoator, Blumeria grammis, and Mycosphaerella fijiensis.
9. The method of claim 3 , wherein the fungal disease or disorder is selected from the group consisting of apple scab, speckled leaf blotch of wheat, leaf spot of sugarbeets, leaf spot of peanut, cucumber anthracnose, wheat leaf rust, grape powdery mildew, wheat powdery mildew, and black sigatoka.
10. The method of claim 4 , wherein R 1 is fluoro.
11. The method of claim 4 , wherein R 2 is fluoro.
12. The method of claim 4 , wherein R 1 and R 2 are fluoro.
13. The method of claim 4 , wherein R 4 is phenyl optionally substituted with 0, 1, 2 or 3 independent R 6 .
14. The method of claim 4 , wherein R 4 is phenyl optionally substituted with 0, 1, 2 or 3 independent halo.
15. The method of claim 4 , wherein R 4 is phenyl optionally substituted with 0, 1, 2 or 3 independent fluoro.
16. The method of claim 4 , wherein R 1 is 2,4-difluorophenyl.
17. The method of claim 4 , wherein R 5 is halo.
18. The method of claim 4 , wherein R 3 is heteroaryl optionally substituted with 1, 2 or 3 independent R 5 ; wherein at least one R 5 is halo.
19. The method of claim 4 , wherein:
R 1 is fluoro;
R 2 is fluoro;
R 4 is 2,4-difluorophenyl; and
R 3 is heteroaryl other than 2-pyridyl, substituted with 1, 2 or 3 independent R 5 .
20. The method of claim 4 , 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 .
21. The method of claim 4 , wherein:
R 3 is 2-quinolinyl substituted with 1, 2 or 3 independent R 5 .
22. The method of claim 4 , wherein the compound 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);
1-(6-Cloroquinolin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-1,2,4-triazol-1-yl)propan-2-ol (33);
2-(4-Chloro-2-fluorophenyl)-1-(6-chloroquinoxalin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (34);
1-(6-Chloroquinolin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(4H-1,2,4-triazol-4-yl)propan-2-ol (35);
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);
2-(2,4-Difluorophenyl)-1,1-difluoro-1-(4′-fluoro-[1,1′-biphenyl]-4-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (61).