# US 2013/0158047 A1 · Novel heterocyclic compound, and composition for treating inflammatory diseases using same

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

- Number: US 2013/0158047 A1
- Document ID: US20130158047A1
- Status: Published application
- Kind: A1
- Application number: 13/818,355
- Filed: 2011-08-25
- Published: 2013-06-20
- Earliest claimed: 2010-08-25
- Assignees: NeoPharm, Inc.
- Inventors: Hyung Sub Gwak; Yong Zu Kim; Uk Il Kim; Byeong Deog Park; Tae Kyo Park; Sung Ho Woo; Joung Yul Yun; Dae Yon Lee; Hyang Sook Lee; Jeong Eun Jeon; Se Kyoo Jeong; Hyung Mook Choi
- Web page: https://patentgrep.com/patent/US20130158047A1

## CPC

- C07D 235/08: Radicals containing only hydrogen and carbon atoms
- A61K 8/4946: {Imidazoles or their condensed derivatives, e.g. benzimidazoles}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 11/06: Antiasthmatics
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/04: Antipruritics
- A61P 17/06: Antipsoriatics
- A61P 17/08: Antiseborrheics
- A61P 17/10: Anti-acne agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/04: specific for metastasis
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61Q 19/00: Preparations for care of the skin
- A61Q 19/007: {Preparations for dry skin}
- A61Q 19/008: {Preparations for oily skin}
- C07D 471/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS

## Abstract

Provided are heterocyclic compounds, having effects of treating and preventing inflammatory diseases and treating skin wounds, and particularly, exhibiting effects of recovering disrupted skin barriers, mitigating inflammation, and pruritus. Also, a composition containing the compound as an effective component can be used to mitigate various inflammatory diseases and protease activated receptor-2 (PAR-2)-overexpressed diseases, and can be particularly used as a composition having an anti-inflammatory function in inflammatory skin diseases including atopic dermatitis and the like, by inhibiting PAR-2 activity.

## Claims

### Claim 1

A heterocyclic compound represented by Chemical Formula 1 below:
wherein
R1 is selected from hydrogen, halogen, (C1-C7)alkyl, (C6-C12)aryl, (C3-C6)cycloalkyl, (C6-C12)ar(C1-C7)alkyl, and
R2 and R3 each are independently selected from hydrogen, halogen, (C1-C7)alkyl, (C3-C6)cycloalkyl, (C6-C10)aryl, (C6-C12)ar(C1-C7)alkyl, (C1-C7)alkoxycarbonyl, (C1-C7)alkylamido(C1-C7)alkyl,
R11, R12, R13, R14, R15 and R16 each are independently hydrogen, (C1-C7)alkyl, (C3-C6)cycloalkyl, (C6-C10)aryl, heterocycloalkyl(C6-C12)aryl, or (C3-C12)heteroaryl, and R11 and R12 and R14 and R15 may be linked to each other via alkylene, oxyalkylene, or aminoalkylene to form a 5-membered or 6-membered hetero ring;
n is an integer of 1 to 4;
(C6-C12)aryl of R2 and R3 and the hetero ring formed from R11 and R12 may be further substituted with halogen, hydroxy, (C1-C7)alkyl, (C6-C10)aryl, (C3-C6)cycloalkyl, 5- or 6-membered heterocycloalkyl, 5- or 6-membered heterocycloalkylcarbonyl, 5- or 6-membered cycloalkyl sulfonyl, 5- or 6-membered heteroaryl, (C1-C6)alkoxy, (C1-C7)alkoxycarbonyl, (C1-C7)alkylcarbonyl, (C3-C6)cyclo(C1-C7)alkylcarbonyl, (C6-C10)ar(C1-C7)alkylcarbonyl, (C3-C10)heteroarylcarbonyl, (C6-C10)arylcarbonyl, (C1-C7)alkylsulfonyl, amino(C1-C7)alkylcarbonyl, (C1-C7)alkyloxycarbonyl, (C6-C10)ar(C1-C7)alkyloxycarbonyl, amino(C1-C7)alkylamino, (C1-C7)alkylamido, (C1-C7)alkylcarbamoyl, (C1-C7)alkylsulfoneamido, or
and
R21 and R22 each are independently (C1-C7)alkyl, (C3-C6)cycloalkyl, or (C6-C12)aryl, or R21 and R22 may be linked to each other via alkylene to form a 5- or 6-membered hetero ring, or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The heterocyclic compound of claim 1, wherein,
R1 is (C1-C7)alkyl;
R2 is selected from hydrogen, halogen, (C1-C7)alkyl, (C6-C12)aryl, and (C6-C12)ar(C1-C7)alkyl;
R3 is selected from hydrogen, halogen, (C1-C7)alkyl, (C6-C12)aryl, (C1-C7)alkoxycarbonyl, and
R11 and R12 each are independently hydrogen, (C1-C7)alkyl, (C3-C6)cycloalkyl, (C6-C10)aryl, heterocycloalkyl(C6-C12)aryl, or (C3-C12)heteroaryl, and R11 and R12 may be linked to each other via alkylene, oxyalkylene, or aminoalkylene to form a 5- or 6-membered hetero ring;
n is an integer of 1 to 4;
the (C6-C12)aryl of R2 and R3 and the hetero ring formed from R11 and R12 may be further substituted with halogen, hydroxy, (C1-C7)alkyl, (C6-C10)aryl, (C3-C6)cycloalkyl, 5- or 6-membered heterocycloalkyl, 5- or 6-membered heterocycloalkylcarbonyl, 5- or 6-membered cycloalkyl sulfonyl, 5- or 6-membered heteroaryl, (C1-C6)alkoxy, (C1-C7)alkoxycarbonyl, (C1-C7)alkylcarbonyl, (C3-C6)cyclo(C1-C7)alkylcarbonyl, (C6-C10)ar(C1-C7)alkylcarbonyl, (C3-C10)heteroarylcarbonyl, (C6-C10)arylcarbonyl, (C1-C7)alkylsulfonyl, amino(C1-C7)alkylcarbonyl, (C1-C7)alkyloxycarbonyl, (C6-C10)ar(C1-C7)alkyloxycarbonyl, amino(C1-C7)alkylamino, (C1-C7)alkylamido, (C1-C7)alkylcarbamoyl, (C1-C7)alkylsulfoneamido, or
and
R21 and R22 each are independently (C1-C7)alkyl, (C3-C6)cycloalkyl, or (C6-C12)aryl, or R21 and R22 may be linked to each other via alkylene to form a 5- or 6-membered hetero ring, or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The heterocyclic compound of claim 1, wherein,
R1 is methyl;
R2 is benzyl or phenyl, and the benzyl or phenyl of R2 may be further substituted with halogen, (C1-C7)alkyl, or 5- or 6-membered heterocycloalkyl;
R3 is independently selected from (C1-C7)alkoxycarbonyl and
R11 and R12 each are independently hydrogen, (C1-C7)alkyl, (C3-C6)cycloalkyl, (C6-C10)aryl, heterocycloalkyl(C6-C12)aryl, or (C3-C12)hetero aryl;
R11 and R12 may be linked to each other via alkylene, oxyalkylene, or aminoalkylene to form a 5- or 6-membered hetero ring; and
n is an integer of 1 to 4, or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The heterocyclic compound of claim 1, wherein the heterocyclic compound is represented by Chemical Formula 2 below:
A is CH2 or NR31;
R31 is selected from hydrogen, (C1-C7)alkyl, (C1-C7)alkylcarbonyl, and (C3-C6)cycloalkylcarbonyl; and
R2 is benzyl or phenyl, and the benzyl or phenyl of R2 may be further substituted with halogen, (C1-C7)alkyl, or 5- or 6-membered heterocycloalkyl, or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The heterocyclic compound of claim 1, wherein the heterocyclic compound is selected from the group consisting of the following compounds:
, or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

A pharmaceutical composition, comprising the heterocyclic compound or a pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier.

### Claim 7 (depends on 6)

The pharmaceutical composition of claim 6, which is effective in treating and preventing inflammatory skin diseases covering acne, rosacea, seborrheic dermatitis, atopic dermatitis, post-inflammatory hyperpigmentation (PIH), contact dermatitis, pruritus, psoriasis, Lichen planus, eczema, skin infections, and Netherton Syndrome.

### Claim 8 (depends on 1)

A method for treating skin wounds, comprising administering an effective amount of the heterocyclic compound or a pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

### Claim 9 (depends on 1)

A method for treating and preventing metastasis of cancer, gastrointestinal disease, asthma, and liver cirrhosis, comprising administering an effective amount of the heterocyclic compound of or a pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

### Claim 10 (depends on 1)

A protease activated receptor-2 (PAR-2) inhibitor composition comprising the heterocyclic compound or a pharmaceutically acceptable salt thereof according to claim 1.

### Claim 11 (depends on 1)

A cosmetic composition comprising the heterocyclic compound or a pharmaceutically acceptable salt according to claim 1 and a cosmetically acceptable carrier.

### Claim 12 (depends on 1)

A method for treating an inflammatory skin disease, comprising administering an effective amount of the heterocyclic compound or a pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

### Claim 13 (depends on 12)

The method of claim 12, wherein the inflammatory skin disease comprises acne, rosacea, seborrheic dermatitis, atopic dermatitis, post-inflammatory hyperpigmentation (PIH), contact dermatitis, pruritus, psoriasis, Lichen planus, eczema, skin infections, or Netherton Syndrome.

### Claim 14 (depends on 12)

The method of claim 12, wherein the compound or a pharmaceutically acceptable salt thereof is administered orally, by injection, or by topical application to skin.