# US 2024/0197724 A1 · Therapeutic agent for gait disturbance

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- Number: US 2024/0197724 A1
- Document ID: US20240197724A1
- Status: Published application
- Kind: A1
- Application number: 18/284,941
- Filed: 2022-03-31
- Published: 2024-06-20
- Earliest claimed: 2021-03-31
- Assignees: Nippon Shinyaku Co., Ltd.
- Applicants: Nippon Shinyaku Co., Ltd.
- Inventors: Koji MURAKAMI; Toshiyuki MINAMI
- Web page: https://patentgrep.com/patent/US20240197724A1

## CPC

- A61K 31/4965: Non-condensed pyrazines
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to a therapeutic agent for gait disturbance in a patient with ischemic disease, containing, as an active ingredient, a heterocyclic derivative represented by formula (1) or a pharmaceutically acceptable salt thereof: wherein R1 and R2 are the same or different and each represents optionally substituted aryl; R3 and R4 are the same or different and each represents a hydrogen atom or alkyl; R5 represents a hydrogen atom, alkyl, or a halogen atom; Y represents N or N->0; A represents NR6 and R6 represents a hydrogen atom, alkyl, or the like; D represents alkylene or alkenylene optionally substituted with hydroxy; E represents phenylene or a single bond; G represents O, S, or the like; and Q represents carboxy, alkoxycarbonyl, or the like.

## Claims

### Claim 1

A therapeutic agent for gait disturbance in a patient with ischemic disease, comprising a heterocyclic derivative represented by formula (1) below or a pharmaceutically acceptable salt thereof as an active component:
wherein R1 and R2 are the same or different and each represents aryl optionally substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, alkyl, haloalkyl, arylalkyl, alkoxy, alkylthio, alkoxyalkyl, alkylsulfonyl, hydroxy, amino, monoalkylamino, dialkylamino, carboxy, cyano, and nitro;
R3 and R4 are the same or different and each represents a hydrogen atom or alkyl;
R5 represents a hydrogen atom, alkyl, or a halogen atom;
Y represents N or N->O;
A represents NR6 and R6 represents a hydrogen atom, alkyl, alkenyl, or cycloalkyl; and
D represents alkylene or alkenylene optionally substituted with hydroxy, or A and D are combined with each other to form a divalent group represented by formula (2) below:
wherein r represents an integer of 0 to 2, q represents 2 or 3, and t represents an integer of 0 to 4; and
E represents phenylene or a single bond, or D and E are combined with each other to form a divalent group represented by formula (3) below:
wherein
represents a single bond or a double bond,
wherein u represents an integer of 0 to 2; v represents 0 or 1;
G represents O, S, SO, or SO2; and
Q represents carboxy, alkoxycarbonyl, tetrazolyl, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, or a group represented by formula (4) below:
[Chem. 4]
—CONH—SO2-R7 (4)
wherein R7 represents amino, monoalkylamino, dialkylamino, or hydroxy; or any of groups 1) to 4) below:
1) alkyl,
2) aryl,
3) aryloxy, and
4) a heterocyclic group,
optionally substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, alkyl, haloalkyl, arylalkyl, alkoxy, alkylthio, alkoxyalkyl, alkylsulfonyl, hydroxy, amino, monoalkylamino, dialkylamino, carboxy, cyano, and nitro.

### Claim 2 (depends on 1)

The therapeutic agent for gait disturbance according to claim 1, wherein
in the heterocyclic derivative represented by formula (1), R1 and R2 are the same or different and each represents phenyl optionally substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, alkyl, and alkoxy;
R3 and R4 are the same or different and each represents a hydrogen atom or alkyl;
R5 is a hydrogen atom;
Y is N;
A is NR6, R6 is alkyl;
D is alkylene;
E is a single bond;
G is O; and
Q is carboxy or a group represented by formula (4), and R7 is amino, monoalkylamino, dialkylamino, or hydroxy; or any of groups 1) to 4) below:
1) alkyl,
2) aryl,
3) aryloxy, and
4) a heterocyclic group,
optionally substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, alkyl, haloalkyl, arylalkyl, alkoxy, alkylthio, alkoxyalkyl, alkylsulfonyl, hydroxy, amino, monoalkylamino, dialkylamino, carboxy, cyano, and nitro.

### Claim 3 (depends on 1)

The therapeutic agent for gait disturbance according to claim 1, wherein the patient with ischemic disease is a patient with arteriosclerosis obliterans.

### Claim 4 (depends on 3)

The therapeutic agent for gait disturbance according to claim 3, wherein the patient with arteriosclerosis obliterans is a patient classified into at least one selected from Fontaine Classifications I to IV.

### Claim 5

A therapeutic agent for gait disturbance in a patient with ischemic disease, comprising 2-{4-[N-(5,6-diphenylpyrazine-2-yl)-N-isopropylamino]butyloxy}acetic acid or 2-{4-[N-(5,6-diphenylpyrazine-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide, or a pharmaceutically acceptable salt thereof as an active component.

### Claim 6 (depends on 5)

The therapeutic agent for gait disturbance according to claim 5, wherein the patient with ischemic disease is a patient with arteriosclerosis obliterans.

### Claim 7 (depends on 6)

The therapeutic agent for gait disturbance according to claim 6, wherein the patient with arteriosclerosis obliterans is a patient classified into at least one selected from Fontaine Classifications I to IV.