Pharmaceutical composition for preventing or treating DYRK-related diseases, containing pyridine-based compound as active ingredient

Patent metadata

Field	Value
Publication number	US-10765669-B2
Application number	US-201716470014-A
Country	US
Kind code	B2
Filing date	Dec 15, 2017
Priority date	Dec 15, 2016
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

The present invention relates to a pharmaceutical composition the prevention or treatment of DYRK-related diseases containing a pyridine-based compound as an active ingredient, a pyridine-based compound of the present invention which is used as an active ingredient of the pharmaceutical composition inhibits the activity of DYRK1A with very high efficacy and selectivity, thereby can be used effectively in the prevention or treatment of DYRK-related diseases, such as Down syndrome, degenerative brain diseases, cancer, and metabolic diseases.

First claim

The invention claimed is:

1. A method for treating or improving DYRK-related diseases in a subject in need thereof comprising:
a compound or a pharmaceutically acceptable salt thereof represented by formula 1 below as an active ingredient:

(in formula 1 above,
R 1 is a hydrogen or —NR 6 R 7 , wherein R 6 and R 7 are each independently a hydrogen, a C 1 -C 5 straight or branched chain alkyl or benzyl;
R 2 , R 3 and R 4 are each independently a hydrogen, a halogen, a C 1 -C 5 straight or branched chain alkyl, —NR 8 R 9 , OR 8 , —CN, —NHC(O)R 8 , —SO 2 R 8 , —OS(O) 2 R 8 , pyrrolidine, piperidine, or morpholin, wherein R 8 and R 9 are each independently a hydrogen, a C 1 -C 5 straight or branched chain alkyl, a C 1 -C 5 straight or branched chain alkynyl, a C 6 -C 12 straight or branched chain alkenyl, a C 6 -C 12 aryl, a C 6 -C 12 aryl substituted with a halogen, or a C 6 -C 12 aryl substituted with a trihalogen methyl; and
R 5 is a hydrogen, a C 1 -C 5 straight or branched chain alkyl, unsubstituted 4-piperidine, acetyl-substituted 4-piperidin;
wherein the DYRK-related disease is at least one disease selected from the group consisting of Down syndrome, degenerative brain diseases and metabolic diseases.

2. The method of claim 1 , wherein R 1 is a hydrogen or —NR 6 R 7 , wherein R 6 and R 7 are each independently a hydrogen, a C 1 -C 3 straight or branched chain alkyl;
R 2 , R 3 and R 4 are each independently a hydrogen, —F, —Cl, —Br, —I, a C 1 -C 3 straight or branched chain alkyl, —NR 8 R 9 , OR 8 , —CN, —NHC(O)R 8 , —SO 2 R 8 , —OS(O) 2 R 8 , pyrrolidine, piperidin or morpholin, wherein R 8 and R 9 are each independently a hydrogen, a C 1 -C 5 straight or branched chain alkyl;
R 5 is a hydrogen, a C 1 -C 3 straight or branched chain alkyl, unsubstituted 4-piperidine or acetyl-substituted 4-piperidin.

3. The method of claim 1 , wherein R 1 is a hydrogen or —NR 6 R 7 , wherein R 6 and R 7 are each independently a hydrogen, a C 1 -C 3 straight or branched chain alkyl;
R 2 , R 3 and R 4 are each independently a hydrogen, —F, —Cl, —Br, —I, a C 1 -C 3 straight or branched chain alkyl;
R 5 is a hydrogen, a C 1 -C 3 straight or branched chain alkyl, unsubstituted 4-piperidine or acetyl-substituted 4-piperidin.

4. The method of claim 1 , the degenerative brain disease is Pick's disease, vascular dementia, Alzheimer's disease, Parkinson's disease, Lewy body dementia, frontotemporal dementia, Creutzfeld-Jakob, Huntington's chorea, multiple sclerosis, Guillain-Barre syndrome and Down syndrome.

5. The pharmaceutical composition of claim 1 , the metabolic disease is selected from the group consisting of obesity, diabetes, hypertension, hyperlipidemia, hypercholesterolemia, arteriosclerosis, fatty liver, heart disease, myocardial infarction, angina.

6. A method for inhibiting an activity of a DYRK1A in a subject in need thereof comprising:
administering a composition to the subject, wherein the composition comprising a compound or a pharmaceutically acceptable salt thereof represented by the following formula (1) as an active ingredient:

(in formula 1,
R 1 is a hydrogen or —NR 6 R 7 , wherein R 6 and R 7 are each independently a hydrogen, a C 1 -C 5 straight or branched chain alkyl or benzyl;
R 2 , R 3 and R 4 are each independently a hydrogen, a halogen, a C 1 -C 5 straight or branched chain alkyl, —NR 8 R 9 , OR 8 , —CN, —NHC(O)R 8 , —SO 2 R 8 , —OS(O) 2 R 8 , pyrrolidine, piperidine, or morpholin, wherein R 8 and R 9 are each independently a hydrogen, a C 1 -C 5 straight or branched chain alkyl, a C 1 -C 5 straight or branched chain alkynyl, a C 6 -C 12 straight or branched chain alkenyl, a C 6 -C 12 aryl, a C 6 -C 12 aryl substituted with a halogen, or a C 6 -C 12 aryl substituted with a trihalogen methyl;
R 5 is a hydrogen, a C 1 -C 5 straight or branched chain alkyl, unsubstituted 4-piperidine, acetyl-substituted 4-piperidin.

7. The method of claim 6 wherein R 1 is a hydrogen or —NR 6 R 7 , wherein R 6 and R 7 are each independently a hydrogen, a C 1 -C 3 straight or branched chain alkyl;
R 2 , R 3 and R 4 are each independently a hydrogen, —F, —Cl, —Br, —I, a C 1 -C 3 straight or branched chain alkyl, —NR 8 R 9 , OR 8 , —CN, —NHC(O)R 8 , —SO 2 R 8 , —OS(O) 2 R 8 , pyrrolidine, piperidin or morpholin, wherein R 8 and R 9 are each independently a hydrogen, a C 1 -C 5 straight or branched chain alkyl;
R 5 is a hydrogen, a C 1 -C 3 straight or branched chain alkyl, unsubstituted 4-piperidine or acetyl-substituted 4-piperidin.

8. The method of claim 6 wherein R 1 is a hydrogen or —NR 6 R 7 , wherein R 6 and R 7 are each independently a hydrogen, a C 1 -C 3 straight or branched chain alkyl;
R 2 , R 3 and R 4 are each independently a hydrogen, —F, —Cl, —Br, —I, a C 1 -C 3 straight or branched chain alkyl;
R 5 is a hydrogen, a C 1 -C 3 straight or branched chain alkyl, unsubstituted 4-piperidine or acetyl-substituted 4-piperidin.

Assignees

• Korea Res Inst Bioscience & Biotechnology
• Korea Res Inst Chemical Tech

Inventors

• Cho Sungchan
• Choi Miri
• Lee Joo Youn

Classifications

• A23V2002/00

  Food compositions, function of food ingredients or processes for food or foodstuffs · CPC title

• A23L33/10 Primary

  using additives (addition of substantially indigestible substances A23L33/21) · CPC title

• A61K31/424 Primary

  condensed with heterocyclic ring systems, e.g. clavulanic acid · CPC title

• A23V2200/332

  Promoters of weight control and weight loss · CPC title

• A23V2200/308

  having an effect on cancer prevention · CPC title