Triazolopyridin-3-ones or their salts and pharmaceutical compositions comprising the same

Patent metadata

Field	Value
Publication number	US-11091479-B2
Application number	US-201916712673-A
Country	US
Kind code	B2
Filing date	Dec 12, 2019
Priority date	Dec 14, 2018
Publication date	Aug 17, 2021
Grant date	Aug 17, 2021

Abstract

The present technology provides triazolopyridin-3-ones or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and uses thereof. The triazolopyridin-3-ones or their pharmaceutically acceptable salts exhibit inhibitory activity on VAP-1 and therefore can be usefully applied, e.g., for the treatment and prophylaxis of nonalcoholic hepatosteatosis (NASH).

First claim

The invention claimed is:

1. A compound of Formula X

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;
wherein
R 1 is hydrogen or fluoro; and
R 2 and R 3 , each independently, are selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, —R, and —C≡C—R;
wherein said R is substituted or unsubstituted cyclic ring, optionally containing 1 to 5 heteroatom ring members chosen from O, N, or S, and the cyclic ring is aromatic or non-aromatic.

2. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 1 , wherein R is substituted or unsubstituted aryl.

3. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 1 , wherein R is substituted or unsubstituted phenyl.

4. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 1 , wherein R is substituted or unsubstituted heteroaryl.

5. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 1 , wherein R is substituted or unsubstituted non-aromatic heterocyclic ring.

6. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 1 , wherein the substituted or unsubstituted cyclic ring is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted tetrahydropyridinyl, substituted or unsubstituted pyrazolyl, substituted or unsubstituted benzodioxolyl, substituted or unsubstituted 2,3-dihydro-benzodioxinyl, substituted or unsubstituted benzothiazolyl, substituted or unsubstituted benzoxadiazolyl, substituted or unsubstituted benzotriazolyl, substituted or unsubstituted indazolyl, substituted or unsubstituted pyrrolo[2,3-b]pyridinyl, substituted or unsubstituted 3,4-dihydroquinolin-2-onyl, substituted or unsubstituted 3,4-dihydro-1,4-benzoxazinyl, substituted or unsubstituted 1,4-benzoxazin-3-onyl, substituted or unsubstituted 1,3-dihydro-3,1-benzoxazin-2-onyl, substituted or unsubstituted 2,3-dihydro-pyrido[2,3-b][1,4]oxazinyl, substituted or unsubstituted pyrido[2,3-b][1,4]oxazin-2-onyl, substituted or unsubstituted 3,4-dihydro-pyrido[3,2-b][1,4]oxazinyl, and substituted or unsubstituted pyrido[3,2-b][1,4]oxazin-3-onyl.

7. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 1 , wherein said R 1 is fluoro.

8. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 1 , wherein said R 1 is hydrogen.

9. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 1 , wherein said R 2 is hydrogen and R 3 is halogen, —R, or —C≡C—R.

10. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 1 , wherein
R 1 is fluoro,
R 2 is hydrogen,
R 3 is halogen or —R,
wherein said R is a cyclic ring selected from the group consisting of phenyl and pyrazolyl,
wherein said cyclic ring is substituted with a substituent selected from the group consisting of C 1-6 alkyl, C 1-6 alkylsulfonyl, and piperazinyl.

11. The compound of claim 1 of Formula 11

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;
wherein
R 3 is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted benzodioxolyl.

12. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 11 , wherein R 3 is substituted aryl.

13. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 11 , wherein R 3 is substituted or unsubstituted benzodioxolyl, substituted or unsubstituted benzoxadiazolyl, or phenyl, wherein the phenyl is substituted with C 1-6 alkylcarbonylamino or oxazolyl.

14. The compound of claim 1 of Formula 12

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;
wherein
R 3 is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heterocyclic ring.

15. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 14 , wherein R 3 is substituted or unsubstituted benzodioxolyl, substituted or unsubstituted 2,3-dihydrobenzodioxinyl, substituted or unsubstituted 3,4-dihydroquinolin-2-onyl, substituted or unsubstituted benzothiazolyl, substituted or unsubstituted benzoxadiazolyl, substituted phenyl, or substituted pyridinyl.

16. The compound of claim 1 of Formula 13

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;
wherein
R 3 is substituted or unsubstituted aryl or a substituted or unsubstituted cyclic ring.

17. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 16 , wherein R 3 is substituted or unsubstituted aryl.

18. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 16 , wherein R 3 is substituted or unsubstituted benzoxadiazolyl, substituted or unsubstituted 3,4-dihydroquinolin-2-onyl, substituted or unsubstituted benzodioxolyl, substituted or unsubstituted indazolyl, substituted or unsubstituted pyrazolyl, substituted or unsubstituted benzotriazoyl, substituted or unsubstituted 1,3-dihydro-3,1-benzoxazin-2-onyl, substituted or unsubstituted 1,4-benzoxazin-3-onyl, substituted or unsubstituted 3,4-dihydro-1,4-benzoxazinyl, or substituted phenyl.

19. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 16 , wherein R 3 is a substituted or unsubstituted heterocyclic group.

20. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 16 , wherein R 3 is substituted or unsubstituted heteroaryl.

21. The compound, or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, of claim 16 , wherein R 3 is a cyclic ring selected from the group consisting of phenyl, pyridinyl, benzoxadiazolyl, 3,4-dihydroquinolin-2-onyl, benzodioxolyl, indazolyl, benzotriazolyl, 1,3-dihydro-3,1-benzoxazin-2-onyl, 1,4-benzoxazin-3-onyl, 3,4-dihydro-1,4-benzoxazinyl, or pyrrolo[2,3-b]pyridinyl;
wherein said cyclic ring is optionally substituted with a substituent selected from the group consisting of C 1-6 alkyl, trifluoromethyl, C 1-6 alkoxy, mono- or di-C 1-6 alkylamino, di-C 1-6 alkylaminomethyl, C 1-6 alkyl sulfonyl, morpholinylcarbonyl, morpholinyl, pyrazolyl, oxazolyl, oxadiazolyl, and cyclopropyl-oxadiazolyl.

22. The compound of claim 1 of Formula 14

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;
wherein
R is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heterocyclic ring.

23. The compound, or a s

Assignees

• Yuhan Corp

Inventors

• Han Tae Dong
• Tak Hee Jae
• Kim Eun Kyung
• Kim Dong Hoon
• Choi Su Bin
• Park Sol
• Choi Hyun Ho
• Kim Tae Wang
• Ju Mi Kyeong
• Ha Na Ry

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61K31/5355

  Non-condensed oxazines and containing further heterocyclic rings · CPC title

• A61K31/4709

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title