Aryl or heteroaryl triazolone derivatives or salts thereof, or pharmaceutical compositions comprising the same

Patent metadata

Field	Value
Publication number	US-10899719-B2
Application number	US-201916721020-A
Country	US
Kind code	B2
Filing date	Dec 19, 2019
Priority date	Mar 21, 2018
Publication date	Jan 26, 2021
Grant date	Jan 26, 2021

Abstract

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

First claim

What is claimed is:

1. A compound with a chemical structure of

or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising the compound according to claim 1 , or a stereoisomer, tautomer thereof, or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

3. A method of selectively inhibiting vascular adhesion protein-1 (VAP-1), comprising administering, to a subject in need thereof, a therapeutically effective amount of the compound according to claim 1 , or a stereoisomer, tautomer thereof, or pharmaceutically acceptable salt thereof.

4. A method of treating NASH in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to claim 1 , or a stereoisomer, tautomer thereof, or pharmaceutically acceptable salt thereof.

5. A method of treating a disease mediated by vascular adhesion protein-1 (VAP-1) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to claim 1 , or a stereoisomer or a tautomer thereof, or a pharmaceutically acceptable salt thereof.

6. The method of claim 5 , wherein the disease mediated by VAP-1 is selected from the group consisting of a lipid disorder, lipoprotein disorder, condition or disease which results from chronic fatty or fibrotic degeneration of organs due to accumulated lipid, triglyceride accumulation and subsequent activation of a profibrotic pathway, Type I Diabetes, Type II Diabetes, complication of Type I or Type II Diabetes, chronic intrahepatic cholestatic condition, extrahepatic cholestatic condition, liver fibrosis, acute intraheptic cholestatic condition, obstructive or chronic inflammatory disorder that arises out of improper bile composition, gastrointestinal condition with a reduced uptake of dietary fat or fat-soluble dietary vitamin, inflammatory bowel disease, obesity, metabolic syndrome, combined conditions of dyslipidemia, diabetes and abnormally high body-mass index, persistent infection by intracellular bacteria or parasitic protozoae, non-malignant hyperproliferative disorder, malignant hyperproliferative disorder, colon adenocarcinoma and hepatocellular carcinoma, liver steatosis or associated syndrome, Hepatitis B infection, Hepatitis C infection, cholestatic and fibrotic effects that are associated with alcohol-induced cirrhosis or with viral-borne forms of hepatitis, liver failure or liver malfunction as an outcome of a chronic liver disease or of surgical liver resection, acute myocardial infarction, acute stroke, thrombosis which occurs as an endpoint of chronic obstructive atherosclerosis, osteoarthritis, rheumatoid arthritis, psoriasis, and cerebral infarction, individually or any combination thereof.

7. A method of treating nonalcoholic steatohepatitis (NASH) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition according to claim 2 .

8. A method of treating a disease mediated by vascular adhesion protein-1 (VAP-1) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition according to claim 2 .

9. The method of claim 8 , wherein the disease mediated by VAP-1 is selected from the group consisting of a lipid disorder, lipoprotein disorder, condition or disease which results from chronic fatty or fibrotic degeneration of organs due to accumulated lipid, triglyceride accumulation and subsequent activation of a profibrotic pathway, Type I Diabetes, Type II Diabetes, complication of Type I or Type II Diabetes, chronic intrahepatic cholestatic condition, extrahepatic cholestatic condition, liver fibrosis, acute intraheptic cholestatic condition, obstructive or chronic inflammatory disorder that arises out of improper bile composition, gastrointestinal condition with a reduced uptake of dietary fat or fat-soluble dietary vitamin, inflammatory bowel disease, obesity, metabolic syndrome, combined conditions of dyslipidemia, diabetes and abnormally high body-mass index, persistent infection by intracellular bacteria or parasitic protozoae, non-malignant hyperproliferative disorder, malignant hyperproliferative disorder, colon adenocarcinoma and hepatocellular carcinoma, liver steatosis or associated syndrome, Hepatitis B infection, Hepatitis C infection, cholestatic and fibrotic effects that are associated with alcohol-induced cirrhosis or with viral-borne forms of hepatitis, liver failure or liver malfunction as an outcome of a chronic liver disease or of surgical liver resection, acute myocardial infarction, acute stroke, thrombosis which occurs as an endpoint of chronic obstructive atherosclerosis, osteoarthritis, rheumatoid arthritis, psoriasis, and cerebral infarction, individually or any combination thereof.

Assignees

• Yuhan Corp

Inventors

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

Classifications

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D405/10

  linked by a carbon chain containing aromatic rings · CPC title

• A61P1/16

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