4-phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-based compounds and methods of their use
View Patent ↗Compounds of formula I are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and/or manage diseases and disorders:
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
A 1 is optionally substituted heterocycle;
each R 1 is independently halogen, hydrogen, C(O)R A , OR A , NR B R C , S(O 2 )R A , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;
R 2 is independently halogen, hydrogen, C(O)R A , OR A , NR B R C , S(O 2 )R A , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;
R 3 is hydrogen, C(O)R A , C(O)OR A , or optionally substituted alkyl, alkyl-aryl, alkyl-heterocycle, aryl, or heterocycle;
R 4 is hydrogen or optionally substituted alkyl, alkyl-aryl, alkyl-heterocycle, aryl, or heterocycle;
each R A is independently hydrogen or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;
each R B is independently hydrogen or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;
each R C is independently hydrogen or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle; and
m is 1-4.
2. The compound of claim 1 , which is of the formula:
3. The compound of claim 1 , which is of the formula:
wherein:
each R 5 is independently halogen, hydrogen, C(O)R A , OR A , NR B R C , S(O 2 )R A , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle; and
n is 1-3.
4. The compound of claim 3 , which is of the formula:
5. The compound of claim 1 , which is of the formula:
wherein:
each R 5 is independently halogen, hydrogen, C(O)R A , OR A , NR B R C , S(O 2 )R A , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle; and
n is 1-3.
6. The compound of claim 5 , which is of the formula:
7. The compound of claim 1 , which is of the formula:
wherein:
each R 5 is independently halogen, hydrogen, C(O)R A , OR A , NR B R C , S(O 2 )R A , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle; and
n is 1-3.
8. The compound of claim 7 , which is of the formula:
9. The compound of claim 1 , which is of the formula:
wherein:
each R 5 is independently halogen, hydrogen, C(O)R A , OR A , NR B R C , S(O 2 )R A , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle; and
p is 1-4.
10. The compound of claim 9 , which is of the formula:
11. The compound of claim 1 , which is of the formula:
wherein:
each R 5 is independently halogen, hydrogen, C(O)R A , OR A , NR B R C , S(O 2 )R A , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle; and
q is 1-2.
12. The compound of claim 11 , which is of the formula:
13. The compound of claim 1 , which is of the formula:
wherein:
each R 5 is independently halogen, hydrogen, C(O)R A , OR A , NR B R C , S(O 2 )R A , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle; and
q is 1-2.
14. The compound of claim 13 , which is of the formula:
15. The compound of claim 1 , which is of the formula:
wherein:
each R 5 is independently halogen, hydrogen, C(O)R A , OR A , NR B R C , S(O 2 )R A , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle; and
q is 1-2.
16. The compound of claim 15 , which is of the formula:
17. The compound of claim 1 , wherein R 1 is hydrogen or halogen.
18. The compound of claim 1 , wherein m is 1.
19. The compound of claim 1 , wherein R 2 is hydrogen or amino.
20. The compound of claim 1 , wherein R 3 is hydrogen or lower alkyl.
21. The compound of claim 1 , wherein R 3 is C(O)OR A and R A is alkyl.
22. The compound of claim 1 , wherein R 4 is hydrogen or lower alkyl.
23. A composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient or diluent.
24. A single unit dosage form comprising the composition of claim 23 .