Amino pyrimidine SSAO inhibitors
The present invention provides compounds of the Formula (I), or a pharmaceutically acceptable salt thereof, where n and R1 are defined herein, methods of treating patients for liver disease, and processes for preparing the compounds.
1. A compound of the formula below:
wherein: n is 1 or 2; and
R1 is H or —CH 3 ,
or a pharmaceutically acceptable salt thereof.
2. A compound of the formula below:
wherein: n is 1 or 2; and
R1 is H or —CH 3 ,
or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 2 , wherein n is 1, or a pharmaceutically acceptable salt thereof.
4. The compound according to claim 2 , wherein n is 2, or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 2 , wherein R1 is H, or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 2 , wherein R1 is —CH 3 , or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 2 , which is
or a pharmaceutically acceptable salt thereof.
8. A compound of the formula below
or a pharmaceutically acceptable salt thereof.
9. The compound according to claim 2 , which is provided as a mono or di hydrochloride addition salt, methylsulfonic acid addition salt, or a 4-methylbenzenesulfonic acid addition salt.
10. The compound according to claim 8 , which is (2E)-3-fluoro-2-({[2-(4-methoxypiperidin-1-yl)pyrimidin-5-yl]oxy}methyl)prop-2-en-1-amine 4-methylbenzenesulfonate.
11. A compound, which is (2E)-3-fluoro-2-({[2-(4-methoxypiperidin-1-yl)pyrimidin-5-yl]oxy}methyl)prop-2-en-1-amine 4-methylbenzenesulfonate in crystalline form characterized by an X-ray powder diffraction pattern obtained from a CuKα source (λ=1.54056 Å), which comprises peaks at:
a) 18.6, 19.1, 21.0, 21.9, and 22.4+/−0.2° in 2 theta, or
b) 17.6, 11.0, 16.8, 18.6, 19.1, 21.0, 21.9, 22.4 and 26.1+/−0.2° in 2 theta.
12. A pharmaceutical composition comprising the compound according to claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.
13. A method of treating a patient in need of treatment for non-alcoholic steatohepatitis, wherein the method comprises administering to the patient an effective amount of the pharmaceutical composition according to claim 12 .
14. A method of treating a patient in need of treatment for non-alcoholic steatohepatitis, wherein the method comprises administering to the patient an effective amount of the compound according to claim 2 , or a pharmaceutically acceptable salt thereof.
15. The compound according to claim 1 , wherein n is 1, or a pharmaceutically acceptable salt thereof.
16. The compound according to claim 1 , wherein n is 2, or a pharmaceutically acceptable salt thereof.
17. The compound according to claim 1 , wherein R1 is H, or a pharmaceutically acceptable salt thereof.
18. The compound according to claim 1 , wherein R1 is —CH 3 , or a pharmaceutically acceptable salt thereof.
19. A pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.
20. A method of treating a patient in need of treatment for non-alcoholic steatohepatitis, wherein the method comprises administering to the patient an effective amount of the pharmaceutical composition according to claim 19 .
21. A pharmaceutical composition comprising the compound according to claim 7 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.
22. A method of treating a patient in need of treatment for non-alcoholic steatohepatitis, wherein the method comprises administering to the patient an effective amount of the pharmaceutical composition according to claim 21 .
23. A pharmaceutical composition comprising the compound according to claim 8 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.
24. A method of treating a patient in need of treatment for non-alcoholic steatohepatitis, wherein the method comprises administering to the patient an effective amount of the pharmaceutical composition according to claim 23 .
25. A pharmaceutical composition comprising the compound according to claim 9 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.
26. A method of treating a patient in need of treatment for non-alcoholic steatohepatitis, wherein the method comprises administering to the patient an effective amount of the pharmaceutical composition according to claim 25 .
27. A pharmaceutical composition comprising the compound according to claim 10 and a pharmaceutically acceptable carrier, diluent or excipient.
28. A method of treating a patient in need of treatment for non-alcoholic steatohepatitis, wherein the method comprises administering to the patient an effective amount of the pharmaceutical composition according to claim 27 .
29. A pharmaceutical composition comprising the compound according to claim 11 and a pharmaceutically acceptable carrier, diluent or excipient.
30. A method of treating a patient in need of treatment for non-alcoholic steatohepatitis, wherein the method comprises administering to the patient an effective amount of the pharmaceutical composition according to claim 29 .
31. The compound according to claim 8 , which is (E)-3-fluoro-2-[[2-(4-,methoxy-1-piperidyl)pyrimidin-5-yl]oxymethyl]prop-2-en-1-amine dihydrochloride.
32. A pharmaceutical composition comprising the compound according to claim 31 and a pharmaceutically acceptable carrier, diluent or excipient.
33. A method of treating a patient in need of treatment for non-alcoholic steatohepatitis, wherein the method comprises administering to the patient an effective amount of the pharmaceutical composition according to claim 32 .