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 tetrazolyl;
R 1 is halo;
R 2 is halo;
R 3 is independently halo, haloalkoxy, haloalkoxyalkyl, or hydroxyl;
R 4 is aryl, optionally substituted with 0, 1, 2 or 3 independent R 3 ;
R 5 is H or —P(O)(OH) 2 ;
R 6 is H or halo; and
n is 0, 1, 2 or 3.
2. The compound of claim 1 , wherein R 1 and R 2 are fluoro.
3. The compound of claim 1 , wherein R 3 is haloalkoxyalkyl or haloalkoxy, and n is 1.
4. The compound of claim 1 , wherein R 3 is 2,2,2-trifluoroethoxy, and n is 1.
5. The compound of claim 1 , wherein R 4 is phenyl optionally substituted with 0, 1, 2, or 3 independent halo.
6. The compound of claim 1 , wherein R 4 is phenyl optionally substituted with 2 halo.
7. The compound of claim 1 , wherein R 4 is phenyl substituted with 2 fluoro.
8. The compound of claim 1 , wherein R 5 is hydrogen.
9. The compound of claim 1 , wherein
R 1 and R 2 are fluoro;
R 3 is 2,2,2-trifluoroethoxy and n is 1;
R 4 is difluorophenyl; and
R 5 and R 6 are hydrogen.
10. A pharmaceutical composition comprising the compound of claim 1 , or salt, solvate, hydrate or prodrug thereof, and a pharmaceutically acceptable carrier.
11. A method of inhibiting metalloenzyme activity comprising contacting the compound of claim 1 , or a salt, solvate, hydrate, or prodrug thereof, with a metalloenzyme which is lanosterol demethylase (CYP51).
12. A method of treating a subject suffering from or susceptible to a metalloenzyme-related disorder or disease, comprising administering to the subject an effective amount of a compound of claim 1 , or salt, solvate, hydrate or prodrug thereof.
13. A compound of Formula I, or salt thereof, wherein:
MBG is tetrazolyl;
R 1 is halo;
R 2 is halo;
R 3 is independently halo, haloalkoxy, or haloalkoxyalkyl;
R 4 is aryl, optionally substituted with 0, 1, 2 or 3 independent R 3 ;
R 5 is —P(O)(OH) 2 ;
R 6 is hydrogen; and
n is 0, 1, 2 or 3.
14. The compound of claim 13 , wherein R 1 and R 2 are fluoro.
15. The compound of claim 13 , wherein R 3 is haloalkoxyalkyl or haloalkoxy, and n is 1.
16. The compound of claim 13 , wherein R 3 is 2,2,2-trifluoroethoxy, and n is 1.
17. The compound of claim 13 , wherein R 4 is phenyl substituted with 2 fluoro.
18. The compound of claim 13 , wherein R 5 is hydrogen.
19. The compound of claim 13 , wherein:
R 1 and R 2 are fluoro;
R 3 is 2,2,2-trifluoroethoxy, and n is 1;
R 4 is difluorophenyl; and
R 5 and R 6 are hydrogen.
20. A compound of Formula I, or salt, solvate, hydrate or prodrug thereof, wherein:
MBG is tetrazolyl;
R 1 is fluoro;
R 2 is fluoro;
R 3 is haloalkoxy or haloalkoxyalkyl;
R 4 is phenyl substituted with 1, 2, or 3 fluoro;
R 5 is hydrogen;
R 6 is hydrogen; and
n is 1.
21. The compound of claim 20 , wherein R 3 is 2,2,2-trifluoroethoxy.
22. The compound of claim 20 , wherein R 4 is 2,4-difluorophenyl.
23. The compound of claim 20 , wherein:
R 3 is 2,2,2-trifluoroethoxy; and
R 4 is 2,4-difluorophenyl.
24. The compound or the salt, solvate, hydrate, or prodrug of claim 20 , wherein the compound has the formula:
and wherein R 3 is 2,2,2-trifluoroethoxy.