Tetrahydronaphthyridinyl propionic acid derivatives and uses thereof
The present application relates to use of compounds of formula I for treating or preventing a fibrosis.
1. A method of treating or preventing a fibrosis, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I:
or a pharmaceutically acceptable salt or solvate thereof, wherein:
X 1 -X 2 is CHR 1 —CH 2 , CH═CH, or C(O)—CH 2 ;
R 1 is H or OH;
Q 1 is
Y Y′ is CR 3 ═N, CR 4 ═CR 4 , or C(O)—NH;
R 3 is C 1 -C 3 alkoxy, F, or R 3 , together with R 2 and the carbon atoms to which they are attached, form a phenyl ring;
each R 4 is independently C 1 -C 3 alkoxy, F, or two R 4 , together with the carbon atoms to which they are attached, form a 5- or 6-membered heterocyclic ring comprising one or two heteroatoms selected from N and O;
R 2 is H or together with R 3 and the carbon atoms to which they are attached, form a phenyl ring; and
Q 2 is
2. The method of claim 1 , wherein X 1 -X 2 is CHR 1 —CH 2.
3. The method of claim 2 , wherein R 1 is H.
4. The method of claim 2 , wherein R 1 is OH.
5. The method of claim 1 , wherein X 1 -X 2 is CH═CH.
6. The method of claim 1 , wherein X 1 -X 2 is C(O)—CH 2.
7. The method of claim 1 , wherein Y Y′ is CR 3 ═N.
8. The method of claim 7 , wherein R 3 is methoxy, ethoxy, or propoxy.
9. The method of claim 7 , wherein R 3 , together with R 2 and the carbon atoms to which they are attached, form a phenyl ring.
10. The method of claim 1 , wherein Y Y′ is CR 4 ═CR 4.
11. The method of claim 10 , wherein one of R 4 is methoxy, ethoxy, or propoxy.
12. The method of claim 10 , wherein two R 4 , together with the carbon atoms to which they are attached, form a 5- or 6-membered heterocyclic ring comprising one or two heteroatoms selected from N and O.
13. The method of claim 1 , wherein Y Y′ is C(O)—NH.
14. The method of claim 1 , wherein Q 2 is
15. The method of claim 1 , wherein Q 2 is
16. The method of claim 1 , wherein Q 2 is
17. The method of claim 1 , wherein the compound is selected from:
18. The method of claim 1 , wherein the fibrosis is hepatic fibrosis, pulmonary fibrosis, cardiac fibrosis, renal fibrosis, or cystic fibrosis.