Pyrazole compounds substituted with heteroaryl and pharmaceutical use thereof
Pyrazole compounds substituted with heteroaryl or pharmaceutically acceptable salts thereof that have an SGLT1 inhibitory activity and are useful for a drug, pharmaceutical compositions comprising the same, and pharmaceutical use thereof are disclosed. Specifically, a compound of Formula [X]: wherein R 1 is hydrogen or halogen, R 2 is C 1-6 alkyl or halo-C 1-6 alkyl, Ring Het is substituted pyridyl or optionally substituted pyrazinyl, pyrimidinyl, or pyridazinyl, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising it, and pharmaceutical use thereof is provided.
1. A compound of Formula [X]:
wherein R 1 is hydrogen or halogen;
R 2 is C 1-6 alkyl or halo-C 1-6 alkyl;
Ring Het is:
(1) pyridyl substituted with R 3 ; or
(2) pyrazinyl, pyrimidinyl, or pyridazinyl, optionally substituted with R 4 ;
R 3 is cyano, halogen, or halo-C 1-3 alkyl;
R 4 is halogen, hydroxy, C 1-3 alkyl, halo-C 1-3 alkyl, C 1-3 alkoxy, or —N(R 5 )(R 6 ); and
R 5 and R 6 are each independently hydrogen or C 1-3 alkyl,
or a pharmaceutically acceptable salt thereof.
2. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is halogen.
3. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is halo-C 1-6 alkyl.
4. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Ring Het is pyridyl substituted with R 3 .
5. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Ring Het is pyrazinyl, pyrimidinyl, or pyridazinyl, optionally substituted with R 4 .
6. A compound of Formula [I]:
or a pharmaceutically acceptable salt thereof.
7. A compound of Formula [II]:
or a pharmaceutically acceptable salt thereof.
8. A compound of Formula [III]:
or a pharmaceutically acceptable salt thereof.
9. A compound of Formula [IV]:
or a pharmaceutically acceptable salt thereof.
10. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 7 , and 9 , and a pharmaceutically acceptable carrier.
11. An SGLT1 inhibitor comprising the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 7 , and 9 to a mammal.
12. A method for inhibiting SGLT1 comprising administering a therapeutically effective amount of the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 7 , and 9 to a mammal.
13. The method according to claim 12 , wherein the diabetes is type 2 diabetes.
14. A compound of Formula [IV]:
15. A pharmaceutical composition comprising the compound according to claim 14 , and a pharmaceutically acceptable carrier.
16. A method for inhibiting SGLT1 comprising administering a therapeutically effective amount of the compound according to claim 14 to a mammal.
17. A method for treating diabetes comprising administering a therapeutically effective amount of the compound according to claim 14 to a mammal.
18. The method according to claim 17 , wherein the diabetes is type 2 diabetes.