IP Library Granted Patent US 9,220,265
Granted Patent B2
US 9,220,265 · App. 14/297,065 · Granted Dec 29, 2015

Metalloenzyme inhibitor compounds

Inventors: William J. Hoekstra (Durham, NC); Christopher M. Yates (Raleigh, NC); Robert J. Schotzinger (Raleigh, NC); Michael R. Loso (Carmel, IN); Zachary A. Buchan (Indianapolis, IN); Michael T. Sullenberger (Westfield, IN); Gary D. Gustafson (Zionsville, IN)
Assignee: Viamet Pharmaceuticals, Inc.
A01N43/713A01N25/00A01N43/647A01N43/653A01N43/78C07D401/06C07D401/14C07D409/14C07D417/14
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Quick Facts
Patent No.
US 9,220,265
App. No.
14/297,065
Granted
Dec 29, 2015
Kind
B2
Abstract

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

Claims (234)

1. A method of treating or preventing a metalloenzyme-mediated disease or disorder in or on a plant comprising contacting a composition comprising a compound of Formula I with the plant or seeds;

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 H, halo, alkyl or haloalkyl;

R 2 is H, halo, alkyl or haloalkyl;

R 3 is independently H, alkyl, nitro, cyano, haloalkyl, alkoxy, halo, haloalkoxy, alkenyl, haloalkenyl, cycloalkyl, halocycloalkyl, alkynyl, haloalkynyl, thioalkyl, SF 3 , SF 6 , SCN, SO 2 R 6 , —C(O)-alkyl, —C(O)OH, —C(O)O-alkyl, C(O)H, CH═N—O-alkyl, —CH═N—O-arylalkyl;

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

R 5 is alkyl, haloalkyl, cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each optionally substituted with 0, 1, 2 or 3 independent R 3 ;

R 6 is alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

R 7 is H, alkyl, —Si(R 8 ) 3 , —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)-alkyl optionally substituted with amino;

R 8 is independently alkyl or aryl;

R 9 is independently H, alkyl, halo, or haloalkyl; and

X is O or S.

2. A method of inhibiting metalloenzyme activity in a microorganism on a plant comprising contacting a composition comprising a compound of Formula I with the plant or seeds;

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 H, halo, alkyl or haloalkyl;

R 2 is H, halo, alkyl or haloalkyl;

R 3 is independently H, alkyl, nitro, cyano, haloalkyl, alkoxy, halo, haloalkoxy, alkenyl, haloalkenyl, cycloalkyl, halocycloalkyl, alkynyl, haloalkynyl, thioalkyl, SF 3 , SF 6 , SCN, SO 2 R 6 , —C(O)-alkyl, —C(O)OH, —C(O)O-alkyl, C(O)H, CH═N—O-alkyl, —CH═N—O-arylalkyl;

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

R 5 is alkyl, haloalkyl, cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each optionally substituted with 0, 1, 2 or 3 independent R 3 ;

R 6 is alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

R 7 is H, alkyl, —Si(R 8 ) 3 , —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)-alkyl optionally substituted with amino;

R 8 is independently alkyl or aryl;

R 9 is independently H, alkyl, halo, or haloalkyl; and

X is O or S.

3. A method of treating or preventing a fungal disease or disorder in or on a plant comprising contacting a composition comprising a compound of Formula I with the plant or seeds;

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 H, halo, alkyl or haloalkyl;

R 2 is H, halo, alkyl or haloalkyl;

R 3 is independently H, alkyl, nitro, cyano, haloalkyl, alkoxy, halo, haloalkoxy, alkenyl, haloalkenyl, cycloalkyl, halocycloalkyl, alkynyl, haloalkynyl, thioalkyl, SF 3 , SF 6 , SCN, SO 2 R 6 , —C(O)-alkyl, —C(O)OH, —C(O)O-alkyl, C(O)H, CH═N—O-alkyl, —CH═N—O-arylalkyl;

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

R 5 is alkyl, haloalkyl, cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each optionally substituted with 0, 1, 2 or 3 independent R 3 ;

R 6 is alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

R 7 is H, alkyl, —Si(R 8 ) 3 , —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)-alkyl optionally substituted with amino;

R 8 is independently alkyl or aryl;

R 9 is independently H, alkyl, halo, or haloalkyl; and

X is O or S.

4. A method of treating or preventing fungal growth in or on a plant comprising contacting a composition comprising a compound of Formula I with the plant or seeds;

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 H, halo, alkyl or haloalkyl;

R 2 is H, halo, alkyl or haloalkyl;

R 3 is independently H, alkyl, nitro, cyano, haloalkyl, alkoxy, halo, haloalkoxy, alkenyl, haloalkenyl, cycloalkyl, halocycloalkyl, alkynyl, haloalkynyl, thioalkyl, SF 3 , SF 6 , SCN, SO 2 R 6 , —C(O)-alkyl, —C(O)OH, —C(O)O-alkyl, C(O)H, CH═N—O-alkyl, —C═N—O-arylalkyl;

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

R 5 is alkyl, haloalkyl, cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aryl, heteroaryl, arylalkyl, or heteroaryalkyl, each optionally substituted with 0, 1, 2 or 3 independent R 3 ;

R 6 is alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

R 7 is H, alkyl, —Si(R 8 ) 3 , —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)-alkyl optionally substituted with amino;

R 8 is independently alkyl or aryl;

R 9 is independently H, alkyl, halo, or haloalkyl; and

X is O or S.

5. A method of inhibiting microorganisms in or on a plant comprising contacting a composition comprising a compound of Formula I with the plant or seeds;

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 H, halo, alkyl or haloalkyl;

R 2 is H, halo, alkyl or haloalkyl;

R 3 is independently H, alkyl, nitro, cyano, haloalkyl, alkoxy, halo, haloalkoxy, alkenyl, haloalkenyl, cycloalkyl, halocycloalkyl, alkynyl, haloalkynyl, thioalkyl, SF 3 , SF 6 , SCN, SO 2 R 6 , —C(O)-alkyl, —C(O)OH, —C(O)O-alkyl, C(O)H, CH═N—O-alkyl, —CH═N—O-arylalkyl;

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

R 5 is alkyl, haloalkyl, cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each optionally substituted with 0, 1, 2 or 3 independent R 3 ;

R 6 is alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

R 7 is H, alkyl, —Si(R 8 ) 3 , —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)-alkyl optionally substituted with amino;

R 8 is independently alkyl or aryl;

R 9 is independently H, alkyl, halo, or haloalkyl; and

X is O or S.

6. The method according to claim 5 , further comprising an azole fungicide selected from epoxyconazole, tebuconazole, fluquinconazole, flutriafol, metconazole, myclobutanil, cycproconazole, prothtioconazole and propiconazole.

7. The method according to claim 5 , further comprising a strobilurin fungicide from the group trifloxystrobin, pyraclostrobin, orysastrobin, fluoxastrobin and azoxystrobin.

8. The method of claim 5 , wherein R 1 is fluoro.

9. The method of claim 5 , wherein R 2 is fluoro.

10. The method of claim 5 , wherein R 1 and R 2 are fluoro.

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

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

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

14. The method of claim 5 , wherein R 4 is 2,4-difluorophenyl.

15. The method of claim 5 , wherein R 5 is aryl optionally substituted with 0, 1, 2 or 3 independent R 3 .

16. The method of claim 5 , wherein R 5 is arylalkyl optionally substituted with 0, 1, 2 or 3 independent R 3 .

17. The method of claim 5 , wherein R 5 is heteroarylalkyl optionally substituted with 0, 1, 2 or 3 independent R 3 .

18. The method of claim 5 , wherein R 5 is heteroaryl optionally substituted with 0, 1, 2 or 3 independent R 3 .

19. The method of claim 5 , wherein:

R 1 is fluoro;

R 2 is fluoro;

R 4 is 2,4-difluorophenyl; and

R 5 is aryl optionally substituted with 0, 1, 2 or 3 independent R 3 .

20. The method of claim 5 , wherein:

R 1 is fluoro;

R 2 is fluoro;

R 4 is 2,4-difluorophenyl; and

R 5 is heteroaryl optionally substituted with 0, 1, 2 or 3 independent R 3 .

21. The method of claim 5 , wherein:

R 1 is fluoro;

R 2 is fluoro;

R 4 is 2,4-difluorophenyl; and

R 5 is arylalkyl optionally substituted with 0, 1, 2 or 3 independent R 3 .

22. The method of claim 5 , wherein:

R 5 is benzyl optionally substituted with 0, 1, 2 or 3 independent R 3 .

23. The method of claim 5 , wherein:

R 5 is —CH 2 -heteroaryl optionally substituted with 0, 1, 2 or 3 independent R 3 .

24. The method of claim 5 , wherein:

R 5 is —CH 2 —CF 2 -aryl optionally substituted with 0, 1, 2 or 3 independent R 3 .

25. The method of claim 5 , wherein the compound is one of:

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

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

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

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

4-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yloxy)benzonitrile (5);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(4-fluorophenoxy)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (6);

1-(5-(4-Chlorophenoxy)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-methoxypyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (8);

4-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)methyl)benzonitrile (9);

4-(((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)methyl)-2-fluorobenzonitrile (10);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-phenoxypyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (11); or

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(2,2,2-trifluoro ethoxy)pyridin-2-yl)propan-2-ol (12);

1-(4-((2,4-Difluorobenzyl)oxy)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-(vinyloxy)pyridin-2-yl)propan-2-ol (14);

4-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)thio)methyl)-3-fluorobenzonitrile (15);

4-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)thio)methyl)-3-fluorobenzonitrile (16);

4-((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)-2-fluorobenzonitrile (17);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((2,2,2-trifluoroethyl)thio)pyridin-2-yl)propan-2-ol (18);

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

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(2,2,2-trifluoroethoxy)benzyl)oxy)pyridin-2-yl)propan-2-ol (20);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(trifluoromethoxy)benzyl)oxy)pyridin-2-yl)propan-2-ol (21);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((4-(trifluoromethyl)benzyl)oxy)pyridin-2-yl)propan-2-ol (22);

1-(5-((2,3-Difluorobenzyl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (23);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-((2-fluoro-4-(trifluoromethyl)benzyl)oxy)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (24);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((3-(2,2,2-trifluoroethoxy)benzyl)oxy)pyridin-2-yl)propan-2-ol (25);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((3-(trifluoromethyl)benzyl)oxy)pyridin-2-yl)propan-2-ol (26);

1-(5-((4-Chloro-3-fluorobenzyl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (27);

1-(5-((3,4-Difluorobenzyl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (28);

2-((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)acetonitrile (29);

1-(5-(Benzyloxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (30);

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

1-(5-(But-2-yn-1-yloxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (32);

1-(5-(But-2-yn-1-yloxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(2H-tetrazol-2-yl)propan-2-ol (33);

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

1-(5-((3,5-Difluorobenzyl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (35);

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

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

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

1-(5-(Cyclopropylmethoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (39);

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

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-((4-methoxybenzyl)oxy)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (41);

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

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-isobutoxypyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (43);

1-(5-((2,3-Difluorobenzyl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-1,2,3-triazol-1-yl)propan-2-ol (44);

1-(5-((2,3-Difluorobenzyl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-1,2,4-triazol-1-yl)propan-2-ol (45)

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-((2-fluorobenzyl)oxy)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (46);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((1,1,1-trifluoropropan-2-yl)oxy)pyridin-2-yl)propan-2-ol (47);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(2H-tetrazol-2-yl)-1-(5-((1,1,1-trifluoropropan-2-yl)oxy)pyridin-2-yl)propan-2-ol (48);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(thiophen-2-ylmethoxy)pyridin-2-yl)propan-2-ol (49);

6-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)methyl)nicotinonitrile (50);

6-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)methyl)nicotinonitrile (51);

3-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)methyl)benzonitrile (52);

3-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)methyl)benzonitrile (53);

2-(4-Chloro-2-fluorophenyl)-1-(5-(cyclopropylmethoxy)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (54);

4-(((6-(2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)methyl)benzonitrile (55);

4-(((6-(2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)methyl)benzonitrile (56);

4-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)methyl)-3-fluorobenzonitrile (57);

4-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)methyl)-3-fluorobenzonitrile (58);

3-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)methyl)-4-fluorobenzonitrile (59);

2-(2,4-Difluorophenyl)-1-(5-((3,5-difluoropyridin-2-yl)methoxy)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (60);

6-(((6-(2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)methyl)nicotinonitrile (61);

6-(((6-(2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)methyl)nicotinonitrile (62);

1-(5-(But-2-yn-1-yloxy)pyridin-2-yl)-2-(4-chloro-2-fluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (63);

1-(5-(But-2-yn-1-yloxy)pyridin-2-yl)-2-(4-chloro-2-fluorophenyl)-1,1-difluoro-3-(2H-tetrazol-2-yl)propan-2-ol (64);

5-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)methyl)-2-fluorobenzonitrile (65);

5-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)methyl)-2-fluorobenzonitrile (66);

3-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)methyl)-2-fluorobenzonitrile (67);

3-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)methyl)-2-fluorobenzonitrile (68);

2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-1-(5-isobutoxypyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (69);

2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-1-(5-isobutoxypyridin-2-yl)-3-(2H-tetrazol-2-yl)propan-2-ol (70);

2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)propan-2-ol (71);

2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-3-(2H-tetrazol-2-yl)-1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)propan-2-ol (72);

5-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)methyl)thiophene-2-carbonitrile (73);

5-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)methyl)thiophene-2-carbonitrile (74);

2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(trifluoromethyl)phenoxy)pyridin-2-yl)propan-2-ol (75);

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

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

3-((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)benzonitrile (78);

4-((6-(2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)benzonitrile (79);

4-((6-(2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)benzonitrile (80);

4-((6-(2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)-2-fluorobenzonitrile (81);

4-((6-(2-(4-Chloro-2-fluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)-2-fluorobenzonitrile (82);

4-(((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)methyl)benzonitrile (83);

1-(5-(3-Chlorophenoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (84);

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(3-methoxyphenoxy)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (85);

1-(5-(3,4-Difluorophenoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (86);

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

2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(2-fluorophenoxy)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (88);

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

4-((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)pyridin-3-yl)oxy)-3-fluorobenzonitrile (90);

Methyl 2-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)thio)acetate (91);

1-(5-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (92);

6-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)nicotinonitrile (93);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((5-(trifluoromethyl)pyridin-2-yl)oxy)pyridin-2-yl)propan-2-ol (94);

1-(5-((5-chloropyridin-2-yl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (95);

4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)picolinonitrile (96);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(pyrimidin-2-yloxy)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (97);

1-(5-((5-chloropyrimidin-2-yl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (98);

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

5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)pyrimidine-2-carbonitrile (100);

6-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)nicotinaldehyde (101);

(E)-6-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)nicotinaldehyde O-methyl oxime (102);

(E)-6-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)nicotinaldehyde O-benzyl oxime (103);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)oxy)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (104);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((5-(trifluoromethyl)pyrimidin-2-yl)oxy)pyridin-2-yl)propan-2-ol (105);

1-(5-((5-bromopyridin-2-yl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (106);

2-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)thiazole-5-carbonitrile (107);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(quinolin-2-yloxy)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (108);

1-(5-((5-chlorobenzo[d]thiazol-2-yl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (109);

1-(5-((6-chlorobenzo[d]thiazol-2-yl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (110);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((6-(trifluoromethyl)pyridin-3-yl)oxy)pyridin-2-yl)propan-2-ol (111);

5-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)picolinonitrile (112);

1-(5-((5-chloropyridin-2-yl)methoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (113);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((5-(trifluoromethyl)pyridin-2-yl)methoxy)pyridin-2-yl)propan-2-ol (114);

2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-((6-(trifluoromethyl)pyridin-3-yl)methoxy)pyridin-2-yl)propan-2-ol (115);

1-(5-((6-chloropyridin-3-yl)methoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (116);

1-(5-((2-chloropyridin-4-yl)methoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (117);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(pyridin-4-ylmethoxy)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (118);

1-(5-(2,2-difluoro-2-phenylethoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (119);

1-(5-(2-(4-(difluoromethoxy)phenyl)-2,2-difluoroethoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (120);

1-(5-(2-(4-chlorophenyl)-2,2-difluoroethoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (121);

4-(2-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)-1,1-difluoroethyl)benzonitrile (122);

1-(5-(2-(4-(difluoromethoxy)phenyl)-2-fluoroethoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (123);

2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(2-fluoro-2-phenylethoxy)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (124).

26. 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.

27. The method of claim 5 , wherein the microorganism belongs to at least one genera selected from Blumeria, Podosphaera, Sphaerotheca, Uncinula, Erysiphe, Puccinia, Phakopsora, Gymnosporangium, Hemileia, Uromyces, Alternaria, Cercospora, Cladosporium, Cochliobolus, Colletotrichum, Magnaporthe, Mycosphaerella, Phaeosphaeria, Pyrenophora, Ramularia, Rhyncosporium, Septoria, Venturia, Ustilago, Aspergillus, Penicillium, Drechslera, Fusarium, Botrytis, Gibberella, Rhizoctonia, Pseudocercosporella, Sclerotinia, Helminthosporium, Stagonospora, Exserohilum , and Pyricularia.

28. The method of claim 5 , 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 recondita tritici, Uncinula necator, Blumeria graminis , and Mycosphaerella fijiensis.

29. A composition comprising a compound of Formula (I) and an agriculturally acceptable carrier:

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 H, halo, alkyl or haloalkyl;

R 2 is H, halo, alkyl or haloalkyl;

R 3 is independently H, alkyl, nitro, cyano, haloalkyl, alkoxy, halo, haloalkoxy, alkenyl, haloalkenyl, cycloalkyl, halocycloalkyl, alkynyl, haloalkynyl, thioalkyl, SF 3 , SF 6 , SCN, SO 2 R 6 , —C(O)-alkyl, —C(O)OH, —C(O)O-alkyl, C(O)H, CH═N—O-alkyl, —CH═N—O-arylalkyl;

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

R 5 is alkyl, haloalkyl, cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each optionally substituted with 0, 1, 2 or 3 independent R 3 ;

R 6 is alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

R 7 is H, alkyl, —Si(R 8 ) 3 , —P(O)(OH) 2 , —CH 2 —O—P(O)(OH) 2 , or —C(O)-alkyl optionally substituted with amino;

R 8 is independently alkyl or aryl;

R 9 is independently H, alkyl, halo, or haloalkyl; and

X is O or S.

Assignments (7)
CHANGE OF NAME Recorded Jan 2, 2018
From: VIAMET PHARMACEUTICALS, INC.
To: VIAMET PHARMACEUTICALS (NC), INC.
Reel/Frame 044978/0893 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 2, 2016
From: HOEKSTRA, WILLIAM J.; YATES, CHRISTOPHER M.; SCHOTZINGER, ROBERT J.
To: VIAMET PHARMACEUTICALS, INC.
Reel/Frame 037875/0605 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 2, 2016
From: INNOCRIN PHARMACEUTICALS, INC.
To: VPS-1, INC.
Reel/Frame 037875/0659 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 2, 2016
From: LOSO, MICHAEL R; SULLENBERGER, MICHAEL T.; BUCHAN, ZACHARY A.
To: DOW AGROSCIENCES LLC
Reel/Frame 037875/0555 →
CHANGE OF NAME Recorded Mar 2, 2016
From: VPS-1, INC.
To: VIAMET PHARMACEUTICALS, INC.
Reel/Frame 037980/0281 →
CHANGE OF NAME Recorded Mar 2, 2016
From: VIAMET PHARMACEUTICALS, INC.
To: INNOCRIN PHARMACEUTICALS, INC.
Reel/Frame 037980/0323 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 2, 2016
From: DOW AGROSCIENCES LLC
To: VIAMET PHARMACEUTICALS, INC.
Reel/Frame 037979/0722 →
Continuity (4)
Continuation 13527426 · Jun 19, 2012
Provisional Application 61498570 · Jun 19, 2011
Provisional Application 61611897 · Mar 16, 2012
Related Publication 20140288107A1 · Sep 25, 2014