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 compound of formula (I), or salt thereof, wherein:
MBG is optionally substituted tetrazolyl, optionally substituted triazolyl, or optionally substituted pyrazolyl;
R 1 is halo;
R 2 is halo;
each R 3 is independently alkyl, cyano, haloalkyl, alkoxy, halo, haloalkoxy,
R 4 is aryl optionally substituted with O, 1, 2 or 3 independent R 3 ;
R 5 is H, or —C(O)alkyl optionally substituted with amino;
n is 0, 1, 2 or 3.
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 H.
10. The compound of claim 1 , wherein R 5 is amino substituted acyl.
11. The compound of claim 1 , wherein:
R 1 is fluoro;
R 2 is fluoro;
R 4 is 2,4-difluorophenyl; and
R 5 is H.
12. The compound of claim 1 , wherein:
each R 3 is independently cyano, haloalkyl, alkoxy, halo, haloalkoxy, and n is 1 or 2.
13. The compound of claim 11 , wherein:
each R 3 is independently cyano, haloalkyl, alkoxy, halo, haloalkoxy, and n is 1.
14. The compound of claim 1 , which is one of:
4-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)benzonitrile (1);
2-(2, 4-Difluorophenyl)-1, 1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(trifluoromethyl)phenyl)pyridin-2-yl) propan-2-ol (2);
3-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)benzonitrile (3);
2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(4-isopropoxyphenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (4);
2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(4-fluorophenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (5);
2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(3-(trifluoromethoxy)phenyl)pyridin-2-yl)propan-2-ol (6);
2-(2, 4-Difluorophenyl)-1, 1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(trifluoromethoxy)phenyl)pyridin-2-yl) propan-2-ol (7);
1-(5-(3-Chlorophenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (8);
1-(5-(4-Chlorophenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (9);
2-(2,4-Difluorophenyl)-1-(5-(2,5-difluorophenyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (10);
2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-ol (11);
2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(4-(2,2,3,3,3-pentafluoropropoxy)phenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (12);
2-(2, 4-difluorophenyl)-1, 1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(2, 2, 2-trifluoroethoxy)phenyl)pyridin-2-yl) propan-2-yl 3-aminopropanoate (13);
2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-yl 2-aminoacetate hydrochloride (14);
2-(2,4-Difluorophenyl)-1, 1-difluoro-3-(1H-pyrazol-3-yl)-1-(5-(4-(trifluoro methoxy)phenyl)pyridin-2-yl) propan-2-ol (15);
2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(4-fluorophenyl)pyridin-2-yl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol (16);
2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-1,2,4-triazol-1-yl)-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-ol (17);
2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-1,2,4-triazol-1-yl)-1-(5-(4-(trifluoromethoxy)phenyl)pyridin-2-yl) propan-2-ol (18);
2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-1,2,3-triazol-1-yl)-1-(5-(4-(trifluoromethoxy)phenyl)pyridin-2-yl) propan-2-ol (19);
2-(2,4-Difluorophenyl)-1,1-difluoro-3-(2H-tetrazol-1-yl)-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-ol (20);
2-(2, 4-Difluorophenyl)-1, 1-difluoro-3-(2H-tetrazol-1-yl)-1-(5-(3-(fluorophenyl)pyridin-2-yl) propan-2-ol (21);
2-(2, 4-Difluorophenyl)-1, 1-difluoro-3-(2H-tetrazol-1-yl)-1-(5-(4-(trifluoromethylphenyl)pyridin-2-yl) propan-2-ol (22);
2-(2, 4-Difluorophenyl)-1, 1-difluoro-3-(1H-1,2,3-triazol-1-yl)-1-(5-(4-(trifluoromethylphenyl)pyridin-2-yl) propan-2-ol (23);
4-(6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenol (24);
2-(2,4-Difluorophenyl)-1,1-difluoro-1-(5-(3-isopropylphenyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (25);
2-(2,4-Difluorophenyl)-1-(5-(3,4-difluorophenyl)pyridin-2-yl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (26);
1-(5-(3-(Difluoromethoxy)phenyl)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (27);
2-(2,4-Difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-((trifluoromethyl) thio)phenyl)pyridin-2-yl)propan-2-ol (28).
15. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.