IP Library Granted Patent US 8,796,001
Granted Patent B2
US 8,796,001 · App. 13/527,413 · Granted Aug 5, 2014

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)
Assignee: Viamet Pharmaceuticals, Inc.
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Quick Facts
Patent No.
US 8,796,001
App. No.
13/527,413
Granted
Aug 5, 2014
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 (172)

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

MBG is optionally substituted tetrazoly, 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. 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 3 .

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

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

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

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

13. The compound of claim 1 , 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 .

14. The compound of claim 1 , 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 .

15. The compound of claim 1 , 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 .

16. The compound of claim 15 , wherein:

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

17. The compound of claim 15 , wherein:

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

18. The compound of claim 15 , wherein:

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

19. The compound of claim 1 , which 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-1yl)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-Diflourobenzyl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-diflouro-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); or

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).

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

21. The composition of claim 20 further comprising an additional therapeutic agent.

22. The composition of claim 20 further comprising an additional therapeutic agent that is an anti-cancer agent, antifungal agent, cardiovascular agent, antiinflarnmatory 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.

Assignments (7)
CHANGE OF NAME Recorded Jan 2, 2018
From: VIAMET PHARMACEUTICALS, INC.
To: VIAMET PHARMACEUTICALS (NC), INC.
Reel/Frame 044978/0893 →
CHANGE OF NAME Recorded Nov 5, 2014
From: VPS-1, INC.
To: VIAMET PHARMACEUTICALS, INC.
Reel/Frame 034176/0075 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 5, 2014
From: INNOCRIN PHARMACEUTICALS, INC.
To: VPS-1, INC.
Reel/Frame 034111/0242 →
CHANGE OF NAME Recorded Nov 5, 2014
From: VIAMET PHARMACEUTICALS, INC.
To: INNOCRIN PHARMACEUTICALS, INC.
Reel/Frame 034175/0689 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 20, 2014
From: DOW AGROSCIENCES LLC
To: VIAMET PHARMACEUTICALS, INC.
Reel/Frame 032482/0543 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 11, 2012
From: HOEKSTRA, WILLIAM J.; YATES, CHRISTOPHER M.; SCHOTZINGER, ROBERT J.
To: VIAMET PHARMACEUTICALS, INC.
Reel/Frame 029113/0764 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 11, 2012
From: LOSO, MICHAEL R.; SULLENBERGER, MICHAEL T.; BUCHAN, ZACHARY A.
To: DOW AGROSCIENCES LLC
Reel/Frame 029113/0892 →
Continuity (3)
Provisional Application 61498570 · Jun 19, 2011
Provisional Application 61611897 · Mar 16, 2012
Related Publication 20130005752A1 · Jan 3, 2013