# US 10,765,669 B2 · Pharmaceutical composition for preventing or treating DYRK-related diseases, containing pyridine-based compound as active ingredient

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,765,669 B2
- Document ID: US10765669B2
- Status: Granted
- Kind: B2
- Application number: 16/470,014
- Filed: 2017-12-15
- Published: 2020-03-19
- Granted: 2020-09-08
- Earliest claimed: 2016-12-15
- Assignees: Korea Research Institute of Bioscience and Biotechnology; Korea Research Institute of Chemical Technology
- Applicants: Korea Research Institute of Bioscience and Biotechnology; Korea Research Institute of Chemical Technology
- Inventors: Sungchan Cho; Miri Choi; Joo Youn Lee
- Web page: https://patentgrep.com/patent/US10765669B2

## CPC

- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A23L 33/10: using additives (addition of substantially indigestible substances A23L33/21)
- A61K 31/424: condensed with heterocyclic ring systems, e.g. clavulanic acid
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 35/00: Antineoplastic agents
- A23V 2002/00: Food compositions, function of food ingredients or processes for food or foodstuffs
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A23V: INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION

## 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.

## Claims

### Claim 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,
R1 is a hydrogen or —NR6R7, wherein R6 and R7 are each independently a hydrogen, a C1-C5 straight or branched chain alkyl or benzyl;
R2, R3 and R4 are each independently a hydrogen, a halogen, a C1-C5 straight or branched chain alkyl, —NR8R9, OR8, —CN, —NHC(O)R8, —SO2R8, —OS(O)2R8, pyrrolidine, piperidine, or morpholin, wherein R8 and R9 are each independently a hydrogen, a C1-C5 straight or branched chain alkyl, a C1-C5 straight or branched chain alkynyl, a C6-C12 straight or branched chain alkenyl, a C6-C12 aryl, a C6-C12 aryl substituted with a halogen, or a C6-C12 aryl substituted with a trihalogen methyl; and
R5 is a hydrogen, a C1-C5 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.

### Claim 2 (depends on 1)

The method of claim 1, wherein R1 is a hydrogen or —NR6R7, wherein R6 and R7 are each independently a hydrogen, a C1-C3 straight or branched chain alkyl;
R2, R3 and R4 are each independently a hydrogen, —F, —Cl, —Br, —I, a C1-C3 straight or branched chain alkyl, —NR8R9, OR8, —CN, —NHC(O)R8, —SO2R8, —OS(O)2R8, pyrrolidine, piperidin or morpholin, wherein R8 and R9 are each independently a hydrogen, a C1-C5 straight or branched chain alkyl;
R5 is a hydrogen, a C1-C3 straight or branched chain alkyl, unsubstituted 4-piperidine or acetyl-substituted 4-piperidin.

### Claim 3 (depends on 1)

The method of claim 1, wherein R1 is a hydrogen or —NR6R7, wherein R6 and R7 are each independently a hydrogen, a C1-C3 straight or branched chain alkyl;
R2, R3 and R4 are each independently a hydrogen, —F, —Cl, —Br, —I, a C1-C3 straight or branched chain alkyl;
R5 is a hydrogen, a C1-C3 straight or branched chain alkyl, unsubstituted 4-piperidine or acetyl-substituted 4-piperidin.

### Claim 4 (depends on 1)

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.

### Claim 5 (depends on 1)

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.

### Claim 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,
R1 is a hydrogen or —NR6R7, wherein R6 and R7 are each independently a hydrogen, a C1-C5 straight or branched chain alkyl or benzyl;
R2, R3 and R4 are each independently a hydrogen, a halogen, a C1-C5 straight or branched chain alkyl, —NR8R9, OR8, —CN, —NHC(O)R8, —SO2R8, —OS(O)2R8, pyrrolidine, piperidine, or morpholin, wherein R8 and R9 are each independently a hydrogen, a C1-C5 straight or branched chain alkyl, a C1-C5 straight or branched chain alkynyl, a C6-C12 straight or branched chain alkenyl, a C6-C12 aryl, a C6-C12 aryl substituted with a halogen, or a C6-C12 aryl substituted with a trihalogen methyl;
R5 is a hydrogen, a C1-C5 straight or branched chain alkyl, unsubstituted 4-piperidine, acetyl-substituted 4-piperidin.

### Claim 7 (depends on 6)

The method of claim 6 wherein R1 is a hydrogen or —NR6R7, wherein R6 and R7 are each independently a hydrogen, a C1-C3 straight or branched chain alkyl;
R2, R3 and R4 are each independently a hydrogen, —F, —Cl, —Br, —I, a C1-C3 straight or branched chain alkyl, —NR8R9, OR8, —CN, —NHC(O)R8, —SO2R8, —OS(O)2R8, pyrrolidine, piperidin or morpholin, wherein R8 and R9 are each independently a hydrogen, a C1-C5 straight or branched chain alkyl;
R5 is a hydrogen, a C1-C3 straight or branched chain alkyl, unsubstituted 4-piperidine or acetyl-substituted 4-piperidin.

### Claim 8 (depends on 6)

The method of claim 6 wherein R1 is a hydrogen or —NR6R7, wherein R6 and R7 are each independently a hydrogen, a C1-C3 straight or branched chain alkyl;
R2, R3 and R4 are each independently a hydrogen, —F, —Cl, —Br, —I, a C1-C3 straight or branched chain alkyl;
R5 is a hydrogen, a C1-C3 straight or branched chain alkyl, unsubstituted 4-piperidine or acetyl-substituted 4-piperidin.