Methods of using 4-phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-based compounds
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 method of treating irritable bowel syndrome, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of the formula:
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 method of claim 1 , wherein the compound 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.
3. The method of claim 1 , wherein the compound 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 method of claim 1 , wherein the compound 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.
5. The method of claim 1 , wherein the compound 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.
6. The method of claim 1 , wherein the compound 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.
7. The method of claim 1 , wherein the compound 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.
8. The method of claim 1 , wherein the compound 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.
9. The method of claim 1 , wherein R 1 is hydrogen or halogen.
10. The method of claim 1 , wherein m is 1.
11. The method of claim 1 , wherein R 2 is hydrogen or amino.
12. The method of claim 1 , wherein R 3 is hydrogen or lower alkyl.
13. The method of claim 1 , wherein R 4 is hydrogen or lower alkyl.
14. A method of treating irritable bowel syndrome, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein R 4 is hydrogen or lower alkyl.
15. The method of claim 14 , wherein R 4 is hydrogen.
16. The method of claim 14 , wherein R 4 is ethyl.
17. A method of treating carcinoid syndrome, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of the formula:
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.
18. The method of claim 17 , wherein the compound 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.
19. The method of claim 17 , wherein the compound 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.
20. The method of claim 17 , wherein the compound 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.
21. The method of claim 17 , wherein the compound 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.
22. The method of claim 17 , wherein the compound 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.
23. The method of claim 17 , wherein the compound 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.
24. The method of claim 17 , wherein the compound 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.
25. The method of claim 17 , wherein R 1 is hydrogen or halogen.
26. The method of claim 17 , wherein m is 1.
27. The method of claim 17 , wherein R 2 is hydrogen or amino.
28. The method of claim 17 , wherein R 3 is hydrogen or lower alkyl.
29. The method of claim 17 , wherein R 4 is hydrogen or lower alkyl.