N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamides
Compounds having the structure of Formula (I): and pharmaceutically acceptable salts thereof, wherein X 1 , R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in the specification; pharmaceutical compositions comprising such compounds and salts; use of such compounds and salts to treat or prevent Prolyl endopeptidase fibroblast activation protein (FAP)-mediated conditions; kits comprising such compounds and salts; and methods for manufacturing such compounds and salts.
1. A compound that is N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholino-quinoline-4-carboxamide having the structure:
or a pharmaceutically acceptable salt thereof.
2. A compound that is (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide having the structure:
or a pharmaceutically acceptable salt thereof.
3. The compound or salt of claim 2 that is a non-salt form of (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide having the structure:
4. The compound or salt of claim 2 that is the pharmaceutically acceptable salt of (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide having the structure:
5. A pharmaceutical composition comprising a compound that is (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide having the structure:
or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
6. The pharmaceutical composition of claim 5 , wherein the composition comprises a non-salt form of (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide having the structure:
and one or more pharmaceutically acceptable excipients.
7. The pharmaceutical composition of claim 5 , wherein the composition comprises the pharmaceutically acceptable salt of (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide having the structure:
and one or more pharmaceutically acceptable excipients.
8. A method of treating liver disease in a subject suffering from or susceptible to the liver disease, the method comprising administering to the subject a therapeutically effective amount of a compound that is (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide having the structure:
or a pharmaceutically acceptable salt thereof.
9. The method of claim 8 , wherein the liver disease is nonalcoholic steatohepatitis.
10. The method of claim 8 , wherein the method comprises administering to the subject a therapeutically effective amount of a non-salt form of (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide having the structure:
11. The method of claim 10 , wherein the liver disease is nonalcoholic steatohepatitis.
12. The method of claim 8 , wherein the method comprises administering to the subject a therapeutically effective amount of the pharmaceutically acceptable salt of (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide having the structure:
13. The method of claim 12 , wherein the liver disease is nonalcoholic steatohepatitis.