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WO2025046475A1 - Heterocyclic derivative for use in treating atopic dermatitis - Google Patents

Heterocyclic derivative for use in treating atopic dermatitis Download PDF

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Publication number
WO2025046475A1
WO2025046475A1 PCT/IB2024/058343 IB2024058343W WO2025046475A1 WO 2025046475 A1 WO2025046475 A1 WO 2025046475A1 IB 2024058343 W IB2024058343 W IB 2024058343W WO 2025046475 A1 WO2025046475 A1 WO 2025046475A1
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WO
WIPO (PCT)
Prior art keywords
atopic dermatitis
alkyl
chemical formula
pruritus
present
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/IB2024/058343
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French (fr)
Korean (ko)
Inventor
이지은
공민정
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
JW Pharmaceutical Corp
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JW Pharmaceutical Corp
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Filing date
Publication date
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Publication of WO2025046475A1 publication Critical patent/WO2025046475A1/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Definitions

  • the present invention relates to a heterocyclic derivative for treating atopic dermatitis, and more particularly, to a pharmaceutical composition for preventing or treating atopic dermatitis or pruritus, comprising a compound having the heterocyclic derivative structure of the present invention as an active ingredient.
  • Atopic dermatitis is an inflammatory skin eczematous disease, which is accompanied by severe itching and is characterized by chronic relapse (N Engl J Med., 2021, 384, 1136-43).
  • the cause of atopic dermatitis is a complex interaction of various genetic and environmental factors as well as damage to the skin barrier, skin microbiota imbalance, and immune dysregulation, in which Th2 cells are activated by dendritic cells and innate lymphocytes of the epithelial layer stimulated by external antigens that penetrate through the damaged skin barrier (Dermatol Sin., 2019, 37, 3-11).
  • Activated T cells secrete inflammatory and pruritic cytokines such as IL-4, IL-13, and IL-31, and activate the JAK/STAT signaling system, a downstream signal transducer, thereby inhibiting the production of filaggrin, which plays a skin protective role, and inducing skin barrier damage due to pruritus, thereby aggravating skin inflammation (Allergy, 2018, 73, 1881–1891).
  • cytokines such as IL-4, IL-13, and IL-31
  • JAK/STAT signaling system a downstream signal transducer
  • One object of the present invention is to provide a pharmaceutical composition for preventing or treating atopic dermatitis or pruritus, comprising the compound of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
  • Another object of the present invention is to provide a method for preventing or treating atopic dermatitis or pruritus, comprising administering to a subject in need thereof a compound of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof.
  • Another object of the present invention is to provide a method for preventing or treating atopic dermatitis or pruritus, comprising administering to a subject in need thereof a compound of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof.
  • the present invention provides a use of the compound of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof for treatment.
  • Another object of the present invention is to provide a use of the compound of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof for the manufacture of a medicament for the prevention or treatment of atopic dermatitis or pruritus.
  • the compound of the present invention reduces the expression of inflammation-related cytokine genes, thereby reducing the epidermal thickness in inflamed tissues and having excellent anti-pruritic efficacy, and therefore can be usefully used as a composition for the prevention and treatment of atopic dermatitis and pruritus.
  • Figure 1 schematically shows an experimental method for confirming the effect of the compound of the present invention in a histamine-induced acute pruritus animal model.
  • Figure 2 schematically shows an experimental method for confirming the effect of the compound of the present invention in an IL-31-induced acute pruritus animal model.
  • FIG. 3 shows the results of confirming the number of scratching behaviors in a histamine-induced acute itch animal model.
  • Figure 4 shows the results of confirming the number of scratching behaviors in an IL-31-induced acute itch animal model.
  • FIG. 5 schematically illustrates an experimental method for confirming the effect of the compound of the present invention in an atopic dermatitis animal model.
  • FIG. 6 illustrates the results of H&E staining of skin tissue in the first experiment of an atopic dermatitis animal model.
  • FIG. 7 illustrates the results of confirming the thickness of dermal tissue in the first experiment of an atopic dermatitis animal model.
  • FIG. 8 illustrates the results of H&E staining of skin tissue in the second experiment of an atopic dermatitis animal model.
  • FIG. 9 illustrates the results of confirming the thickness of dermal tissue in the second experiment of an atopic dermatitis animal model.
  • FIG. 10 illustrates the results of confirming the number of scratching behaviors in the first experiment of an atopic dermatitis animal model.
  • FIG. 11 illustrates the results of confirming the number of scratching behaviors in the second experiment of an atopic dermatitis animal model.
  • FIG. 12 illustrates the results of confirming the expression of genes related to inflammation and itching in the first experiment of an atopic dermatitis animal model.
  • Fig. 13 is the result of confirming the gene expression related to inflammation and itching in the second experiment of an atopic dermatitis animal model. [Best mode for carrying out the invention] This is described in detail as follows.
  • R b is H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkylcarbonyl-C 1-6 alkyl, C 2-7 alkenyl, amino, or aminoC 1-6 alkyl, and at least one H of R b may be independently substituted with F, Br, Cl, or I
  • R 2 and R 3 are each independently F, Br, Cl, or I.
  • R a O
  • R b is unsubstituted C 1-3 alkyl.
  • C mn (wherein m and n are each independently an integer of 1 or more) means the number of carbons, for example, 'C 1-6 alkyl' means alkyl having 1 to 6 carbons.
  • alkyl means a straight-chain or branched-chain saturated hydrocarbon group represented by C n H 2n+1 .
  • alkyl examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, isobutyl, n-pentyl, sec-pentyl, tert-pentyl, isopentyl, sec-isopentyl, neo-pentyl, n-hexyl, and the like.
  • alkenyl means an unsaturated hydrocarbon group including at least one carbon-carbon double bond in the alkyl.
  • alkoxy means a monovalent group derived from a straight-chain or branched-chain saturated hydrocarbon moiety represented by OC n H 2n+1 .
  • alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, pentoxy, hexoxy, etc.
  • the compound represented by the chemical formula I may be a compound represented by the following chemical formula II. [Chemical Formula II]
  • the compound represented by chemical formula II corresponds to compound 1 of the present invention, and is also named N-(2-chloro-6-(4-chlorophenoxy)pyridin-4-yl)-4-(methylsulfonyl)-3,4-dihydro-2H-thieno[3,2-g]chromene-7-carboxamide.
  • pharmaceutically acceptable means a compound which is suitable for use in contact with the tissues of a subject (e.g., a human) without excessive toxicity, irritation, allergic response or other problems or complications and having a reasonable benefit/risk ratio and which is within the scope of sound medical judgment.
  • the pharmaceutically acceptable salts of the present invention can be prepared by conventional methods known to those skilled in the art.
  • the compound according to any one of the above (1) to (3) of the present invention reduces the expression of inflammation-related cytokine genes, thereby reducing the epidermal thickness in inflamed tissues and has excellent anti-pruritic efficacy, and therefore can be usefully used as a composition for preventing and treating atopic dermatitis and pruritus.
  • composition comprising a heterocyclic derivative compound, a treatment method using the same, and use thereof
  • the present invention relates to a compound according to any one of the above (1) to (3), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate or a solvate thereof, A pharmaceutical composition comprising the compound as an active ingredient is provided.
  • the present invention provides a pharmaceutical composition for preventing or treating atopic dermatitis or pruritus, comprising a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
  • prevention means any act of inhibiting or delaying the onset of a disease by administering a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof; or a pharmaceutical composition comprising the same.
  • treatment means any act of improving or beneficially changing the symptoms of a subject suspected of having a disease or having an onset of a disease by administering a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof; or a pharmaceutical composition comprising the same.
  • atopic dermatitis is an allergic disease that is worse in dry climates due to an abnormality in the stratum corneum, which acts as a protective barrier on the outermost part of the skin.
  • the main symptoms are severe itching, dry skin, rash, oozing, scabs, and scales, and are mainly accompanied by chronic skin inflammation.
  • the cause of atopic dermatitis is mainly genetic and has been found to be related to immune responses, and in addition, it is thought to be caused by a complex interaction of dry skin, a characteristic of easily feeling itchy skin compared to normal people, infection by bacteria, viruses, and fungi, emotional factors, and environmental factors.
  • the antipruritic activity and the preventive and therapeutic activity for atopic dermatitis of a compound according to any one of (1) to (3) of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof were confirmed.
  • the pharmaceutical composition of the present invention is characterized by reducing the expression of one or more cytokines selected from the group consisting of IL-4, IL-5, IFN- ⁇ , H4R, IL-17, and IL-31.
  • the pharmaceutical composition of the present invention suppresses the expression of inflammatory cytokines, reduces the thickness of the skin epidermis induced by atopic dermatitis, and reduces itching, so it can be usefully used for the prevention or treatment of atopic dermatitis and itching.
  • the pharmaceutical composition of the present invention can be manufactured in a unit dose form or by being placed in a multi-dose container by formulating it using a pharmaceutically acceptable carrier and excipient.
  • the formulation can be prepared by a conventional method used in formulation in the art or by a method disclosed in Remington's Pharmaceutical Science ( 19th ed., 1995). It can be manufactured and can be formulated into various preparations according to each disease or component.
  • a person skilled in the art can administer the pharmaceutical composition of the present invention in an amount that can obtain the maximum effect with the minimum amount without side effects by taking all of the above factors into consideration, and this can be easily determined by a person skilled in the art to which the present invention belongs.
  • the pharmaceutical composition of the present invention can exhibit excellent effects even when used alone, but can be additionally used in combination with various methods such as hormone therapy and drug therapy in order to increase therapeutic efficiency.
  • the present invention relates to a compound according to any one of (1) to (3), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof, Or, the present invention provides a method for preventing or treating atopic dermatitis or pruritus, comprising a step of administering a pharmaceutical composition comprising the same to a subject in need thereof.
  • administration means introducing a predetermined substance into a subject by an appropriate method.
  • the "subject” means all animals, such as rats, mice, and livestock, including humans, which have developed or may develop atopic dermatitis or pruritus, and may specifically be mammals including humans, but is not limited thereto.
  • the method for preventing or treating atopic dermatitis or pruritus of the present invention may be a method for administering a therapeutically effective amount of a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.
  • terapéuticaally effective amount in the present invention means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and not causing side effects, which can be determined by those skilled in the art based on factors including the patient's sex, age, weight, health status, type and severity of the disease, activity of the drug, sensitivity to the drug, administration method, administration time, administration route, excretion rate, treatment period, drugs used in combination or simultaneously, and other factors well known in the medical field.
  • a specific therapeutically effective amount for a specific patient will depend on various factors including the type and degree of response to be achieved, the specific composition including whether other agents are used depending on the case, the patient's age, weight, general health status, sex and diet, administration time, administration route and excretion rate of the composition, treatment period, drugs used together or simultaneously with the specific composition, and various other factors. It is preferable to apply differently according to factors and similar factors well known in the pharmaceutical field.
  • the method for preventing or treating atopic dermatitis or pruritus of the present invention includes not only treating the disease itself before the onset of symptoms, but also inhibiting or avoiding the symptoms thereof by administering a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof, or a pharmaceutical composition comprising the same.
  • the prophylactic or therapeutic dosage of a specific active ingredient will vary depending on the nature and severity of the disease or condition, and the route by which the active ingredient is administered. The dosage and frequency of administration will vary depending on the age, weight, and response of the individual patient.
  • the method for preventing or treating atopic dermatitis or pruritus of the present invention may further include administering a therapeutically effective amount of an additional active agent helpful in preventing or treating the disease together with the compound according to any one of (1) to (3), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.
  • the additional active agent may exhibit a synergistic or additive effect together with the compound according to any one of (1) to (3), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.
  • the present invention relates to a compound according to any one of (1) to (3), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof, or a pharmaceutical agent comprising the same for preventing or treating atopic dermatitis or pruritus.
  • the present invention provides a use of a composition.
  • the present invention provides a use of a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof, or a pharmaceutical composition comprising the same, for the manufacture of a medicament for preventing or treating atopic dermatitis or pruritus.
  • a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof may be mixed with a pharmaceutically acceptable excipient, a diluent, a carrier, etc., and may be manufactured into a complex preparation together with other active agents to have a synergistic effect.
  • the acute pruritus animal model a standardized pruritus model, was used to confirm the acute pruritus inhibitory effect of compound 1 (N-(2-chloro-6-(4-chlorophenoxy)pyridin-4-yl)-4-(methylsulfonyl)-3,4-dihydro-2H-thieno[3,2-g]chromene-7-carboxamide) (Figs. 1 and 2).
  • the drug was used at 75 mg/kg of compound 1 prepared with excipients (10% DMSO, 20% PEG400, 10% Tween80, 60% 0.1 M NaHCO3 ) .
  • Example 2 Evaluation of the efficacy of the compound of the present invention in an atopic dermatitis animal model The effect of compound 1 on atopic dermatitis was confirmed using the EC (Epicutaneous) OVA sensitization animal model, which is an atopic dermatitis animal model (Fig. 5). Specifically, the drug was used at 75 mg/kg of compound 1 prepared with excipients (10% DMSO, 20% PEG400, 10% Tween80, 60% 0.1 M NaHCO3 ) .
  • each animal was placed in an opaque acrylic cage, a video was recorded for 1 hour, and the number of times the animal scratched using the hind legs was measured to evaluate the itch behavior.
  • the thickness of the epidermis tissue of the group administered 75 mg/kg of compound 1 was reduced by about 12.5% (1st, Figs. 6 and 7) and about 8.5% (2nd, Figs. 8 and 9) compared to the vehicle administration group.
  • the number of scratching behaviors was significantly reduced by about 84.2% (1st, Fig.

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Abstract

The present invention relates to heterocyclic derivatives for use in treating atopic dermatitis and, more specifically, to a pharmaceutical composition for preventing or treating atopic dermatitis or pruritus, comprising, as an active ingredient, a compound having a heterocyclic derivative structure, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.

Description

【발명의 설명】 【발명의 명칭】 아토피성 피부염 치료용 헤테로환형 유도체 【기술분야】 본 발명은 아토피성 피부염 치료용 헤테로환형 유도체에 관한 것으로, 구체적으로 본 발명의 헤테로환형 유도체 구조를 갖는 화합물을 유효성분으로 포함하는 아토피성 피부염 또는 가려움증의 예방 또는 치료용 약학적 조성물에 관한 것이다. 【배경기술】 아토피 피부염은 염증성 피부 습진 질환으로, 심한 가려움증을 동반하며 만성적으로 재발하는 특징을 보인다 (N Engl J Med., 2021, 384, 1136-43). 아토피 피부염의 발병원인으로는 다양한 유전적, 환경적 요인뿐만 아니라 피부장벽의 손상과 피부 미생물 불균형, 면역 조절 이상이 복합적으로 상호작용하는데, 손상된 피부장벽을 통해 침투한 외부 항원에 자극된 상피층의 수지상세포와 선천성 림프구에 의해 Th2 세포가 활성화된다 (Dermatol Sin., 2019, 37, 3-11). 활성화된 T 세포는 IL-4, IL-13, IL-31 등과 같은 염증 및 가려움 유발 사이토카인을 분비하고, 하위 신호 전달자인 JAK/STAT 신호 체계를 활성화시킴으로써 피부 보호 역할을 하는 필라그린 (filaggrin)의 생성을 억제함과 동시에 가려움에 의한 피부 장벽 손상을 유발하여 피부 염증을 악화시킨다 (Allergy, 2018, 73, 1881–1891). 현재 스테로이드 제제가 아토피성 피부염에 가장 효과적인 것으로 알려져 있으나 장기간 사용 시 피부층이 얇아지는 피부 위축증 발병의 문제와 아토피성 피부염에 대한 내성이 생기는 문제가 있어, 새로운 치료제 개발이 시급한 실정이다. 【발명의 내용】 【기술적 과제】 본 발명자들은 아토피성 피부염 및 가려움증에 우수한 효과를 갖는 신규 치료제를 개발하기 위해 예의 노력한 결과, 본 발명의 화합물이 염증 관련 사이토카인 유전자 발현을 감소시켜 염증 조직에서 표피 두께를 감소시키고 우수한 항소양 효능을 가짐을 확인함으로써 본 발명을 완성하였다. 【기술적 해결방법】 본 발명의 하나의 목적은 본 발명의 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물을 유효성분으로 포함하는, 아토피성 피부염 또는 가려움증의 예방 또는 치료용 약학적 조성물을 제공하는 것이다. 본 발명의 다른 목적은 본 발명의 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물을 이를 필요로 하는 개체에 투여하는 단계를 포함하는, 아토피성 피부염 또는 가려움증의 예방 또는 치료 방법을 제공하는 것이다. 본 발명의 또 다른 목적은 아토피성 피부염 또는 가려움증의 예방 또는 치료를 위한 본 발명의 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물의 용도를 제공하는 것이다. 본 발명의 또 다른 목적은 아토피성 피부염 또는 가려움증의 예방 또는 치료용 약제의 제조를 위한 본 발명의 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물의 용도를 제공하는 것이다. 【발명의 효과】 본 발명의 화합물은 염증 관련 사이토카인 유전자 발현을 감소시켜 염증 조직에서 표피 두께를 감소시키고 우수한 항소양 효능을 가지므로, 아토피성 피부염 및 가려움증의 예방 및 치료용 조성물로서 유용하게 사용될 수 있다. 【도면의 간단한 설명】 도 1은 히스타민 유도 급성 가려움증 동물모델에서 본 발명의 화합물의 효과를 확인하기 위한 실험 방법을 개략적으로 나타낸 것이다. 도 2는 IL-31 유도 급성 가려움증 동물모델에서 본 발명의 화합물의 효과를 확인하기 위한 실험 방법을 개략적으로 나타낸 것이다. 도 3은 히스타민 유도 급성 가려움증 동물모델에서 긁는 행동 횟수를 확인한 결과이다. 도 4는 IL-31 유도 급성 가려움증 동물모델에서 긁는 행동 횟수를 확인한 결과이다. 도 5는 아토피성 피부염 동물모델에서 본 발명의 화합물의 효과를 확인하기 위한 실험 방법을 개략적으로 나타낸 것이다. 도 6은 아토피성 피부염 동물모델의 1 차 실험에서 피부조직의 H&E 염색 결과를 나타낸 것이다. 도 7은 아토피성 피부염 동물모델의 1 차 실험에서 진피 조직의 두께를 확인한 결과이다. 도 8은 아토피성 피부염 동물모델의 2 차 실험에서 피부조직의 H&E 염색 결과를 나타낸 것이다. 도 9는 아토피성 피부염 동물모델의 2 차 실험에서 진피 조직의 두께를 확인한 결과이다. 도 10은 아토피성 피부염 동물모델의 1 차 실험에서 긁는 행동 횟수를 확인한 결과이다. 도 11은 아토피성 피부염 동물모델의 2 차 실험에서 긁는 행동 횟수를 확인한 결과이다. 도 12는 아토피성 피부염 동물모델의 1 차 실험에서 염증 및 가려움증에 관한 유전자 발현을 확인한 결과이다. 도 13은 아토피성 피부염 동물모델의 2 차 실험에서 염증 및 가려움증에 관한 유전자 발현을 확인한 결과이다. 【발명의 실시를 위한 최선의 형태】 이를 구체적으로 설명하면 다음과 같다. 한편, 본 발명에서 개시된 각각의 설명 및 실시형태는 각각의 다른 설명 및 실시 형태에도 적용될 수 있다. 즉, 본 발명에서 개시된 다양한 요소들의 모든 조합이 본 발명의 범주에 속한다. 또한, 하기 기술된 구체적인 서술에 의하여 본 발명의 범주가 제한된다고 볼 수 없다. 헤테로환형 유도체 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물 본 발명은 하기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물을 제공한다. (1) 하기 화학식 I로 표시되는 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물: [화학식 I] 【Description of the invention】 【Title of the invention】 Heterocyclic derivative for treating atopic dermatitis 【Technical field】 The present invention relates to a heterocyclic derivative for treating atopic dermatitis, and more particularly, to a pharmaceutical composition for preventing or treating atopic dermatitis or pruritus, comprising a compound having the heterocyclic derivative structure of the present invention as an active ingredient. 【Background art】 Atopic dermatitis is an inflammatory skin eczematous disease, which is accompanied by severe itching and is characterized by chronic relapse (N Engl J Med., 2021, 384, 1136-43). The cause of atopic dermatitis is a complex interaction of various genetic and environmental factors as well as damage to the skin barrier, skin microbiota imbalance, and immune dysregulation, in which Th2 cells are activated by dendritic cells and innate lymphocytes of the epithelial layer stimulated by external antigens that penetrate through the damaged skin barrier (Dermatol Sin., 2019, 37, 3-11). Activated T cells secrete inflammatory and pruritic cytokines such as IL-4, IL-13, and IL-31, and activate the JAK/STAT signaling system, a downstream signal transducer, thereby inhibiting the production of filaggrin, which plays a skin protective role, and inducing skin barrier damage due to pruritus, thereby aggravating skin inflammation (Allergy, 2018, 73, 1881–1891). Currently, steroid preparations are known to be the most effective for atopic dermatitis, but there is a problem of skin atrophy in which the skin layer becomes thin when used for a long period of time, and a problem of developing resistance to atopic dermatitis, so that the development of a new treatment agent is urgently needed. 【Contents of the invention】 【Technical problem】 As a result of our diligent efforts to develop a novel treatment agent having excellent effects on atopic dermatitis and pruritus, we have completed the present invention by confirming that the compound of the present invention reduces the expression of inflammation-related cytokine genes, thereby reducing the thickness of the epidermis in inflamed tissues and having excellent anti-itch efficacy. 【Technical solution】 One object of the present invention is to provide a pharmaceutical composition for preventing or treating atopic dermatitis or pruritus, comprising the compound of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient. Another object of the present invention is to provide a method for preventing or treating atopic dermatitis or pruritus, comprising administering to a subject in need thereof a compound of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof. Another object of the present invention is to provide a method for preventing or treating atopic dermatitis or pruritus, comprising administering to a subject in need thereof a compound of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof. The present invention provides a use of the compound of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof for treatment. Another object of the present invention is to provide a use of the compound of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof for the manufacture of a medicament for the prevention or treatment of atopic dermatitis or pruritus. [Effect of the invention] The compound of the present invention reduces the expression of inflammation-related cytokine genes, thereby reducing the epidermal thickness in inflamed tissues and having excellent anti-pruritic efficacy, and therefore can be usefully used as a composition for the prevention and treatment of atopic dermatitis and pruritus. [Brief description of the drawings] Figure 1 schematically shows an experimental method for confirming the effect of the compound of the present invention in a histamine-induced acute pruritus animal model. Figure 2 schematically shows an experimental method for confirming the effect of the compound of the present invention in an IL-31-induced acute pruritus animal model. Figure 3 shows the results of confirming the number of scratching behaviors in a histamine-induced acute itch animal model. Figure 4 shows the results of confirming the number of scratching behaviors in an IL-31-induced acute itch animal model. FIG. 5 schematically illustrates an experimental method for confirming the effect of the compound of the present invention in an atopic dermatitis animal model. FIG. 6 illustrates the results of H&E staining of skin tissue in the first experiment of an atopic dermatitis animal model. FIG. 7 illustrates the results of confirming the thickness of dermal tissue in the first experiment of an atopic dermatitis animal model. FIG. 8 illustrates the results of H&E staining of skin tissue in the second experiment of an atopic dermatitis animal model. FIG. 9 illustrates the results of confirming the thickness of dermal tissue in the second experiment of an atopic dermatitis animal model. FIG. 10 illustrates the results of confirming the number of scratching behaviors in the first experiment of an atopic dermatitis animal model. FIG. 11 illustrates the results of confirming the number of scratching behaviors in the second experiment of an atopic dermatitis animal model. FIG. 12 illustrates the results of confirming the expression of genes related to inflammation and itching in the first experiment of an atopic dermatitis animal model. Fig. 13 is the result of confirming the gene expression related to inflammation and itching in the second experiment of an atopic dermatitis animal model. [Best mode for carrying out the invention] This is described in detail as follows. Meanwhile, each of the invention disclosed The description and embodiments may also be applied to each other description and embodiment. That is, all combinations of various elements disclosed in the present invention fall within the scope of the present invention. In addition, the scope of the present invention should not be considered to be limited by the specific descriptions described below. Heterocyclic derivative compound, stereoisomer thereof, pharmaceutically acceptable salt thereof, hydrate thereof, or solvate thereof The present invention provides a compound according to any one of the following (1) to (3), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof. (1) A compound represented by the following chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof: [Chemical Formula I]

상기 화학식 I에서, R1은 -S(=O)(=Ra)Rb이고, Ra는 =O 또는 =NH이고, Rb는 H, C1-6알킬, C1-6알콕시-C1-6알킬, C1-6알킬카보닐-C1-6알킬, C2-7알켄일, 아미노, 또는 아미노C1-6알킬이고, Rb의 적어도 하나의 H는 각각 독립적으로 F, Br, Cl 또는 I로 치환될 수 있으며; R2 및 R3는 각각 독립적으로 F, Br, Cl 또는 I이다. (2) 상기 (1)에 있어서, Ra는 =O이고, Rb는 치환되지 않은 C1-3알킬이다. 본 발명에서 "Cm-n" (여기서 m 및 n은 각각 독립적으로 1 이상의 정수)은 탄소의 개수를 의미하며, 예를 들면, 'C1-6알킬'은 탄소 수가 1 내지 6인 알킬을 의미한다. 본 발명에서 "알킬"은 다른 언급이 없으면, CnH2n+1로 표시되는 직쇄형 또는 분지쇄형의 포화탄화수소기를 의미한다. 알킬의 예로서는, 메틸, 에틸, n-프로필, 아이소프로필, n-부틸, sec-부틸, tert-부틸, 아이소부틸, n-펜틸, sec-펜틸, tert- 펜틸, 아이소펜틸, sec-아이소펜틸, neo-펜틸, n-헥실 등을 들 수 있으나, 이에 제한되지 않는다. 본 발명에서 "알켄일"은 다른 언급이 없으면, 상기 알킬에서 적어도 하나의 탄소-탄소 이중결합을 포함하는 불포화탄화수소기를 의미한다. 본 발명에서 "알콕시"는 다른 언급이 없으면, OCnH2n+1로 표시되는 직쇄형 또는 분지쇄형의 포화탄화수소 모이어티로부터 유래하는 1가 기를 의미한다. 알콕시의 예로서는, 메톡시, 에톡시, 프로폭시, 이소프로폭시, n-부톡시, sec- 부톡시, tert-부톡시, 펜톡시, 헥속시 등을 들 수 있으나, 이에 제한되지 않는다. (3) 상기 (1) 또는 (2)에 있어서, 상기 화학식 I로 표시되는 화합물은 하기 화학식 II로 표시되는 화합물일 수 있다. [화학식 II] In the above chemical formula I, R 1 is -S(=O)(=R a )R b , R a is =O or =NH, R b is H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkylcarbonyl-C 1-6 alkyl, C 2-7 alkenyl, amino, or aminoC 1-6 alkyl, and at least one H of R b may be independently substituted with F, Br, Cl, or I; R 2 and R 3 are each independently F, Br, Cl, or I. (2) In the above (1), R a is =O, R b is unsubstituted C 1-3 alkyl. In the present invention, "C mn " (wherein m and n are each independently an integer of 1 or more) means the number of carbons, for example, 'C 1-6 alkyl' means alkyl having 1 to 6 carbons. In the present invention, unless otherwise stated, "alkyl" means a straight-chain or branched-chain saturated hydrocarbon group represented by C n H 2n+1 . Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, isobutyl, n-pentyl, sec-pentyl, tert-pentyl, isopentyl, sec-isopentyl, neo-pentyl, n-hexyl, and the like. In the present invention, unless otherwise stated, "alkenyl" means an unsaturated hydrocarbon group including at least one carbon-carbon double bond in the alkyl. In the present invention, unless otherwise stated, "alkoxy" means a monovalent group derived from a straight-chain or branched-chain saturated hydrocarbon moiety represented by OC n H 2n+1 . Examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, pentoxy, hexoxy, etc. (3) In the above (1) or (2), the compound represented by the chemical formula I may be a compound represented by the following chemical formula II. [Chemical Formula II]

화학식 II로 표시되는 화합물은 본 발명의 화합물 1에 해당하며, N-(2- 클로로-6-(4-클로로페녹시)피리딘-4-일)-4-(메틸설포닐)-3,4-디히드로-2H- 티에노[3,2-g]크로메네-7-카복사미드로도 명명된다. 본 발명에서 용어 "약학적으로 허용 가능한"은 과도한 독성, 자극, 알러지 반응 또는 기타 문제점 또는 합병증 없이 이득/위험 비가 합리적이어서 대상체 (예컨대, 인간)의 조직과 접촉하여 사용하기에 적합하며 건전한 의학적 판단의 범주 이내인 화합물을 의미한다. 본 발명의 약학적으로 허용 가능한 염은 당업계 통상의 기술자에게 공지된 통상적인 방법에 의해 제조될 수 있다. 본 발명에 있어서 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물은 1개 이상의 비대칭 탄소 중심을 가질 수 있으며, 이에 따라 라세믹 혼합물을 포함하는 에난티오머 혼합물, 단일의 에난티오머 (광학 이성질체), 부분입체이성질체 혼합물 및 단일의 부분입체이성질체로서 존재할 수 있다. 이러한 이성질체는 종래기술, 예를 들어 관 크로마토그래피 또는 HPLC 등의 분할에 의해 분리가 가능하다. 또는, 공지된 배열의 광학적으로 순수한 출발물질 및/또는 시약을 사용하여 입체특이적으로 합성할 수 있다. 본 발명에 있어서 "수화물"은 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물 또는 이의 약학적으로 허용 가능한 염과 물이 비공유적 분자간 힘으로 결합되어 있는 것으로, 화학양론적 또는 비화학양론적의 양의 물을 포함하는 것일 수 있다. 본 발명에 있어서 "용매화물"은 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물 또는 이의 약학적으로 허용 가능한 염과, 물이 아닌 용매가 비공유적 분자간 힘으로 결합되어 있는 것으로, 용매를 화학양론적 또는 비화학양론적 양으로 포함할 수 있다. 본 발명의 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 용매화물은 염증 관련 사이토카인 유전자 발현을 감소시켜 염증 조직에서 표피 두께를 감소시키고 우수한 항소양 효능을 가지므로, 아토피성 피부염 및 가려움증의 예방 및 치료용 조성물로서 유용하게 사용될 수 있다. 헤테로환형 유도체 화합물을 포함하는 조성물, 이를 이용한 치료방법 및 이의 용도 본 발명은 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물을 유효성분으로 포함하는 약학적 조성물을 제공한다. 본 발명은 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물을 유효성분으로 포함하는 아토피성 피부염 또는 가려움증의 예방 또는 치료용 약학적 조성물을 제공한다. 본 발명에서 "예방"은 본 발명의 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물; 또는 이를 포함하는 약학적 조성물의 투여에 의해 질환의 발병을 억제시키거나 지연시키는 모든 행위를 의미한다. 본 발명에서 "치료"는 본 발명의 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물; 또는 이를 포함하는 약학적 조성물의 투여에 의해 질환의 의심 및 발병 개체의 증상이 호전되거나 이롭게 변경되는 모든 행위를 의미한다. 본 발명에서 "아토피성 피부염 (atopic dermatitis)"은 피부 가장 바깥에서 보호벽 역할을 하는 각질층에 이상이 생긴 것으로 건조한 기후에서 더욱 심해지는 알러지 질환 중 하나이다. 주요 증상은 심한 가려움증, 피부건조, 발진, 진물, 부스럼딱지, 인비늘 등으로 주로 만성 피부염증이 동반된다. 아토피성 피부염의 원인은 주로 유전적인 요소가 많고 면역 반응과 관련되어 있는 것으로 밝혀져 있으며, 그 밖에 건조한 피부, 정상인에 비해 쉽게 피부 가려움증을 느끼는 특성, 세균, 바이러스 및 곰팡이 등에 의한 감염, 정서적 요인 및 환경적 요인 등이 서로 복합적으로 작용하여 일어나는 것으로 여겨진다. 본 발명에서 "가렴움증 (소양증)"은 피부 질환에서 가장 주요하게 나타나는 증상이며, 생리적인 자기 보호 기능으로 외부의 유해하거나 자극이 되는 물질로부터 피부를 보호하기 위해 나타나는 증상이다. 가려움증은 다양한 원인에 의해 유발되는데, 상처, 발진 등의 이차적인 피부 병변을 유발하며, 가려워서 긁게 되면 가려움증 유발 물질에 염증성 인자가 동시에 분비되어 통증을 동반한 가려움증이 더욱 심해지는 악순환이 발생하게 된다. 관련하여 본 발명의 구체적인 일 실시예에서는, 본 발명의 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물의 항소양 활성 및 아토피성 피부염에 대한 예방 및 치료 활성을 확인하였다. 본 발명의 약학적 조성물은 IL-4, IL-5, IFN-γ, H4R, IL-17 및 IL-31로 이루어진 군에서 선택되는 하나 이상의 사이토카인의 발현을 감소시키는 것을 특징으로 한다. 이와 같이 본 발명의 약학적 조성물은 염증성 사이토카인의 발현을 억제하고 아토피성 피부염이 유도된 피부 표피의 두께를 감소시키며 가려움증을 감소시키므로, 아토피성 피부염 및 가려움증의 예방 또는 치료에 유용하게 사용될 수 있다. 본 발명의 약학적 조성물은 약학적으로 허용 가능한 담체 및 부형제를 이용하여 제제화하여 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 제제는 당업계에서 제제화에 사용되는 통상의 방법 또는 Remington's Pharmaceutical Science(19th ed., 1995)에 개시되어 있는 방법으로 제조될 수 있으며, 각 질환 또는 성분에 따라 다양한 제제로 제제화될 수 있다. 본 발명의 약학적 조성물은 목적하는 방법에 따라 경구 투여 (oral administration) 또는 비경구 투여 (parenteral administration)할 수 있다. 본 발명의 약학적 조성물의 약학적 유효량, 유효 투여량은 약학적 조성물의 제제화 방법, 투여 방식, 투여 시간 및/또는 투여 경로 등에 의해 다양해질 수 있으며, 또한 약학적 조성물의 투여로 달성하고자 하는 반응의 종류와 정도, 투여 대상이 되는 개체의 종류, 연령, 체중, 일반적인 건강 상태, 질병의 증세나 정도, 성별, 식이, 배설, 해당 개체에 동시 또는 이시에 함께 사용되는 약물 기타 조성물의 성분 등을 비롯한 여러 인자 및 의약 분야에서 잘 알려진 유사 인자에 따라 다양해질 수 있다. 당해 기술 분야에서 통상의 지식을 가진 자는 목적하는 치료에 효과적인 투여량을 용이하게 결정하고 처방할 수 있다. 즉, 당업자는 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양으로 본 발명의 약학적 조성물을 투여할 수 있으며, 이는 본 발명이 속하는 기술 분야의 통상의 기술자에 의해 용이하게 결정될 수 있다. 본 발명의 약학적 조성물은 단독으로 사용하여도 우수한 효과를 발휘할 수 있으나, 치료 효율을 증가시키기 위하여 추가적으로 호르몬 치료, 약물 치료 등의 다양한 방법들과 병용하여 사용될 수 있다. 본 발명은 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물, 또는 이를 포함하는 약학적 조성물을 이를 필요로 하는 개체에 투여하는 단계를 포함하는 아토피성 피부염 또는 가려움증의 예방 또는 치료 방법을 제공한다. 본 발명에서 "투여"는 적절한 방법으로 개체에게 소정의 물질을 도입하는 것을 의미한다. 본 발명에서 "개체"는 아토피성 피부염 또는 가려움증이 발병하였거나 발병할 수 있는 인간을 포함한 쥐, 생쥐, 가축 등의 모든 동물을 의미하며, 구체적으로 인간을 포함하는 포유동물일 수 있으나, 이에 제한되는 것은 아니다. 본 발명의 아토피성 피부염 또는 가려움증의 예방 또는 치료 방법은 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물을 치료학적으로 유효한 양으로 투여하는 것일 수 있다. 본 발명에서 "치료학적으로 유효한 양"이란 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며 부작용을 일으키지 않을 정도의 양을 의미하며, 이는 환자의 성별, 연령, 체중, 건강상태, 질병의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로, 배출 비율, 치료 기간, 배합 또는 동시에 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 당업자에 의해 결정될 수 있다. 특정 환자에 대한 구체적인 치료학적으로 유효한 양은 달성하고자 하는 반응의 종류와 정도, 경우에 따라 다른 제제가 사용되는지 여부를 비롯한 구체적 조성물, 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료기간, 구체적 조성물과 함께 사용되거나 동시 사용되는 약물을 비롯한 다양한 인자와 의약 분야에 잘 알려진 유사 인자에 따라 다르게 적용하는 것이 바람직하다. 본 발명의 아토피성 피부염 또는 가려움증의 예방 또는 치료 방법은 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물 또는 이를 포함하는 약학적 조성물을 투여함으로써, 징후의 발현 전에 질병 그 자체를 다룰 뿐 아니라, 이의 징후를 저해하거나 피하는 것을 또한 포함한다. 질환의 관리에 있어서, 특정 활성 성분의 예방적 또는 치료학적 용량은 질병 또는 상태의 특성과 심각도, 그리고 활성 성분이 투여되는 경로에 따라 다양할 것이다. 용량 및 투여 빈도는 개별 환자의 연령, 체중 및 반응에 따라 다양할 것이다. 적합한 용량 용법은 이러한 인자를 당연히 고려하는 이 분야의 통상의 지식을 가진 자에 의해 쉽게 선택될 수 있다. 또한, 본 발명의 아토피성 피부염 또는 가려움증의 예방 또는 치료 방법은 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물과 함께 질환의 예방 또는 치료에 도움이 되는 추가적인 활성 제제의 치료학적으로 유효한 양의 투여를 더 포함할 수 있다. 추가적인 활성제제는 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물과 함께 시너지 효과 또는 상가적 효과를 나타낼 수 있다. 본 발명은 아토피성 피부염 또는 가려움증의 예방 또는 치료를 위한 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물, 또는 이를 포함하는 약학적 조성물의 용도를 제공한다. 본 발명은 아토피성 피부염 또는 가려움증의 예방 또는 치료용 약제의 제조를 위한, 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물, 또는 이를 포함하는 약학적 조성물의 용도를 제공한다. 약제의 제조를 위하여 본 발명의 상기 (1) 내지 (3) 중 어느 하나에 따른 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물에 약학적으로 허용 가능한 보조제, 희석제, 담체 등을 혼합할 수 있으며, 기타 활성제제와 함께 복합 제제로 제조되어 상승 작용을 가질 수도 있다. 【발명의 실시를 위한 형태】 이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다. 실시예 1. 본 발명의 화합물의 항소양 효능 평가 표준화된 가려움증 모델인 급성 가려움증 동물모델을 이용하여 화합물 1 (N- (2-클로로-6-(4-클로로페녹시)피리딘-4-일)-4-(메틸설포닐)-3,4-디히드로-2H- 티에노[3,2-g]크로메네-7-카복사미드)의 급성 가려움증 억제효과를 확인하였다 (도 1 및 도 2). 구체적으로, 약물은 화합물 1을 부형제 (10 % DMSO, 20 % PEG400, 10 % 트윈80, 60 % 0.1 M NaHCO3)에 75 mg/kg으로 조제하여 사용하였다. 급성 가려움증 동물모델로서 9 주령의 ICR 암컷 생쥐를 1 주일 순화를 거쳐 안정화시킨 후 실험에 사용하였다. 실험 24 시간 전 흡입마취제로 마취 후 클리퍼를 이용하여 목덜미 부위를 깨끗하게 제모하였다. 그 다음 히스타민과 IL- 31을 각각 피내주사하여 피부 소양증을 유도하였다. 약물은 경구투여하였다. 각 실험 그룹을 하기 표 1 및 표 2에 나타내었다. [표 1] 히스타민 유도 급성 가려움증 동물모델 No 그룹 투여물질 용량 투여 부피 투여 경로 N . (유도제+약물) (mg/kg) (mL/kg) (유도제+약물) (개체수) 1 정상군 (saline) 살린+비히클 - 10 피내+경구 10 대조군 히스타민+비히 2 (vehicle 클 - 10 피내+경구 10 ) 실험군 히스타민+화합 3 (compoun 75 10 피내+경구 10 d 1) 물 1 [표 2] IL-31 유도 급성 가려움증 동물모델 투여 No. 그룹 투여물질 용량 투여 경로 N (유도제+약물) 부피 (mg/kg) (유도제+약물) (개체수) (mL/kg) 1 정상군 PBS (PBS) +비히클 - 10 피내+경구 10 2 대조군 (vehicle) IL-31+ 비히클 - 10 피내+경구 10 실험군 IL-31+ 화합물 3 (compound 1 75 10 피내+경구 10 1) 각 동물을 불투명 아크릴 케이지에 넣고 동영상 촬영 후 반복 재생하여, 뒷다리를 사용하여 긁는 횟수를 측정하여 가려움 행동을 평가하였다. 그 결과, 화합물 1 투여 시 긁는 행동의 횟수는 히스타민 유도 동물모델 및 IL-31 유도 동물모델에서 비히클 투여 대비 각각 74.8 %, 38.4 % 수준으로 감소되었다 (도 3 및 도 4). 실시예 2. 아토피성 피부염 동물모델에서 본 발명의 화합물의 효능 평가 아토피성 피부염 동물모델인 EC (Epicutaneous) OVA 감작 동물모델을 이용하여 화합물 1의 아토피 피부염에 대한 효과를 확인하였다 (도 5). 구체적으로, 약물은 화합물 1을 부형제 (10 % DMSO, 20 % PEG400, 10 % 트윈80, 60 % 0.1 M NaHCO3)에 75 mg/kg으로 조제하여 사용하였다. 아토피성 피부염 동물모델로서 6~7 주령의 balb/c 암컷 생쥐를 1 주일 순화를 거쳐 안정화시킨 후 실험에 사용하였다. 실험 24 시간 전 흡입마취제로 마취 후 클리퍼를 이용하여 등 부위에 있는 털을 깨끗하게 제모하였다. 등 부위를 3M 테이프로 6 회 자극한 후, 1.5 x 1.5 cm 길이의 멸균 거즈에 100㎕살린 내 200 ㎍의 OVA를 도포하고 멸균 투명 필름 (TegadermTM)으로 고정하였다. 3 주 간격으로 주 2 회씩 (Day 0, 3, 21, 24, 42, 45) OVA 자극을 주어 아토피 피부염을 유발하였다. 약물은 OVA 감작기간동안 매일 경구투여하였으며 실험은 2 회 반복 수행하였다. 각 실험 그룹을 하기 표 3 및 표 4에 나타내었다. [표 3] 아토피성 피부염 동물모델 1 차 실험 투여 No. 그룹 투여물질 용량 투여 경로 N (유도제+약물) 부피 (mg/kg) (유도제+약물) (개체수) (mL/kg) 1 정상군 (sham) 살린+비히클 - 10 경피+경구 5 2 대조군 (vehicle) OVA+비히클 - 10 경피+경구 5 실험군 3 (compound OVA+화합물 1 75 10 경피+경구 5 1) [표 4] 아토피성 피부염 동물모델 2 차 실험 No. 그룹 투여물질 투여 용량 투여 경로 N (유도제+약물) 부피 (mg/kg) (유도제+약물) (개체수) (mL/kg) 1 정상군 (sham) 살린+비히클 - 10 경피+경구 4 2 대조군 (vehicle) OVA+비히클 - 10 경피+경구 6 실험군 3 (compound OVA+화합물 1 75 10 경피+경구 4 1) 마우스 피부조직의 조직병리학적 평가를 위해 피부 조직을 분리한 후 파라핀 고정을 실시하고, 헤마톡실린-에오신 (H&E) 염색을 통해 표피의 두께 변화를 확인하였다. 또한, 피부 조직에서 RNA를 분리하여 정량적 실시간 PCR (quantitative real-time PCR)을 통해 염증 관련 사이토카인 유전자 발현을 함께 확인하였다. 또한, 각 동물을 불투명 아크릴 케이지에 넣고 1 시간 동영상 촬영 후 반복재생하여, 뒷다리를 사용하여 긁는 횟수를 측정하여 가려움 행동을 평가하였다. H&E 염색을 통해 등 피부 조직을 분석한 결과, 화합물 1을 75 mg/kg 투여한 군의 진피 (epidermis) 조직의 두께가 비히클 투여군에 비해 약 12.5 % (1 차, 도 6 및 도 7), 약 8.5 % (2 차, 도 8 및 도 9) 수준으로 감소된 것을 확인하였다. 긁는 행동의 횟수는 비히클 투여군에 비해 약 84.2 % (1 차, 도 10), 약 94.3 % (2 차, 도 11)로 현저히 감소하였다. 또한, 피부 조직에서 유전자 발현을 측정한 결과, 화합물 1 투여군에서 염증 및 가려움증에 관한 유전자 발현이 비히클 투여군 대비 감소한 것으로 나타났다 (도 12 및 도 13). 이상으로 본 발명의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시예일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다. The compound represented by chemical formula II corresponds to compound 1 of the present invention, and is also named N-(2-chloro-6-(4-chlorophenoxy)pyridin-4-yl)-4-(methylsulfonyl)-3,4-dihydro-2H-thieno[3,2-g]chromene-7-carboxamide. The term "pharmaceutically acceptable" as used herein means a compound which is suitable for use in contact with the tissues of a subject (e.g., a human) without excessive toxicity, irritation, allergic response or other problems or complications and having a reasonable benefit/risk ratio and which is within the scope of sound medical judgment. The pharmaceutically acceptable salts of the present invention can be prepared by conventional methods known to those skilled in the art. In the present invention, the compound according to any one of (1) to (3) above may have one or more asymmetric carbon centers, and thus may exist as an enantiomer mixture including a racemic mixture, a single enantiomer (optical isomer), a diastereomeric mixture, and a single diastereoisomer. Such isomers are known in the art, For example, separation is possible by resolution such as column chromatography or HPLC. Alternatively, it can be stereospecifically synthesized using optically pure starting materials and/or reagents of a known arrangement. In the present invention, the "hydrate" is a compound according to any one of (1) to (3) above, or a pharmaceutically acceptable salt thereof, and water are bound by noncovalent intermolecular forces, and may contain a stoichiometric or nonstoichiometric amount of water. In the present invention, the "solvate" is a compound according to any one of (1) to (3) above, or a pharmaceutically acceptable salt thereof, and a solvent other than water are bound by noncovalent intermolecular forces, and may contain a stoichiometric or nonstoichiometric amount of the solvent. The compound according to any one of the above (1) to (3) of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate or a solvate thereof, reduces the expression of inflammation-related cytokine genes, thereby reducing the epidermal thickness in inflamed tissues and has excellent anti-pruritic efficacy, and therefore can be usefully used as a composition for preventing and treating atopic dermatitis and pruritus. Composition comprising a heterocyclic derivative compound, a treatment method using the same, and use thereof The present invention relates to a compound according to any one of the above (1) to (3), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate or a solvate thereof, A pharmaceutical composition comprising the compound as an active ingredient is provided. The present invention provides a pharmaceutical composition for preventing or treating atopic dermatitis or pruritus, comprising a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient. In the present invention, "prevention" means any act of inhibiting or delaying the onset of a disease by administering a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof; or a pharmaceutical composition comprising the same. In the present invention, "treatment" means any act of improving or beneficially changing the symptoms of a subject suspected of having a disease or having an onset of a disease by administering a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof; or a pharmaceutical composition comprising the same. In the present invention, "atopic dermatitis" is an allergic disease that is worse in dry climates due to an abnormality in the stratum corneum, which acts as a protective barrier on the outermost part of the skin. The main symptoms are severe itching, dry skin, rash, oozing, scabs, and scales, and are mainly accompanied by chronic skin inflammation. The cause of atopic dermatitis is mainly genetic and has been found to be related to immune responses, and in addition, it is thought to be caused by a complex interaction of dry skin, a characteristic of easily feeling itchy skin compared to normal people, infection by bacteria, viruses, and fungi, emotional factors, and environmental factors. In the present invention, "pruritus (itching)" is the most important symptom in skin diseases, and is a symptom that appears to protect the skin from external harmful or irritating substances as a physiological self-protection function. Itching is caused by various causes, and causes secondary skin lesions such as wounds and rashes, and when itching is scratched, inflammatory factors are secreted simultaneously with the itching-causing substances, resulting in a vicious cycle in which the itching accompanied by pain becomes more severe. In relation to this, in a specific embodiment of the present invention, the antipruritic activity and the preventive and therapeutic activity for atopic dermatitis of a compound according to any one of (1) to (3) of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof were confirmed. The pharmaceutical composition of the present invention is characterized by reducing the expression of one or more cytokines selected from the group consisting of IL-4, IL-5, IFN-γ, H4R, IL-17, and IL-31. As such, the pharmaceutical composition of the present invention suppresses the expression of inflammatory cytokines, reduces the thickness of the skin epidermis induced by atopic dermatitis, and reduces itching, so it can be usefully used for the prevention or treatment of atopic dermatitis and itching. The pharmaceutical composition of the present invention can be manufactured in a unit dose form or by being placed in a multi-dose container by formulating it using a pharmaceutically acceptable carrier and excipient. The formulation can be prepared by a conventional method used in formulation in the art or by a method disclosed in Remington's Pharmaceutical Science ( 19th ed., 1995). It can be manufactured and can be formulated into various preparations according to each disease or component. The pharmaceutical composition of the present invention can be administered orally or parenterally depending on the intended method. The pharmaceutically effective amount and effective dosage of the pharmaceutical composition of the present invention can vary depending on the method of formulating the pharmaceutical composition, the administration method, the administration time, and/or the administration route, and also can vary depending on various factors including the type and degree of the response to be achieved by the administration of the pharmaceutical composition, the type, age, weight, general health condition, symptoms or degree of the disease, sex, diet, excretion, drugs used simultaneously or simultaneously in the subject, other components of the composition, and similar factors well known in the medical field. A person having ordinary knowledge in the relevant technical field can easily determine and prescribe an effective dosage for the intended treatment. That is, a person skilled in the art can administer the pharmaceutical composition of the present invention in an amount that can obtain the maximum effect with the minimum amount without side effects by taking all of the above factors into consideration, and this can be easily determined by a person skilled in the art to which the present invention belongs. The pharmaceutical composition of the present invention can exhibit excellent effects even when used alone, but can be additionally used in combination with various methods such as hormone therapy and drug therapy in order to increase therapeutic efficiency. The present invention relates to a compound according to any one of (1) to (3), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof, Or, the present invention provides a method for preventing or treating atopic dermatitis or pruritus, comprising a step of administering a pharmaceutical composition comprising the same to a subject in need thereof. In the present invention, "administration" means introducing a predetermined substance into a subject by an appropriate method. In the present invention, the "subject" means all animals, such as rats, mice, and livestock, including humans, which have developed or may develop atopic dermatitis or pruritus, and may specifically be mammals including humans, but is not limited thereto. The method for preventing or treating atopic dermatitis or pruritus of the present invention may be a method for administering a therapeutically effective amount of a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof. The term "therapeutically effective amount" in the present invention means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and not causing side effects, which can be determined by those skilled in the art based on factors including the patient's sex, age, weight, health status, type and severity of the disease, activity of the drug, sensitivity to the drug, administration method, administration time, administration route, excretion rate, treatment period, drugs used in combination or simultaneously, and other factors well known in the medical field. A specific therapeutically effective amount for a specific patient will depend on various factors including the type and degree of response to be achieved, the specific composition including whether other agents are used depending on the case, the patient's age, weight, general health status, sex and diet, administration time, administration route and excretion rate of the composition, treatment period, drugs used together or simultaneously with the specific composition, and various other factors. It is preferable to apply differently according to factors and similar factors well known in the pharmaceutical field. The method for preventing or treating atopic dermatitis or pruritus of the present invention includes not only treating the disease itself before the onset of symptoms, but also inhibiting or avoiding the symptoms thereof by administering a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof, or a pharmaceutical composition comprising the same. In the management of a disease, the prophylactic or therapeutic dosage of a specific active ingredient will vary depending on the nature and severity of the disease or condition, and the route by which the active ingredient is administered. The dosage and frequency of administration will vary depending on the age, weight, and response of the individual patient. An appropriate dosage regimen can be readily selected by a person skilled in the art who naturally takes these factors into account. In addition, the method for preventing or treating atopic dermatitis or pruritus of the present invention may further include administering a therapeutically effective amount of an additional active agent helpful in preventing or treating the disease together with the compound according to any one of (1) to (3), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof. The additional active agent may exhibit a synergistic or additive effect together with the compound according to any one of (1) to (3), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof. The present invention relates to a compound according to any one of (1) to (3), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof, or a pharmaceutical agent comprising the same for preventing or treating atopic dermatitis or pruritus. The present invention provides a use of a composition. The present invention provides a use of a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof, or a pharmaceutical composition comprising the same, for the manufacture of a medicament for preventing or treating atopic dermatitis or pruritus. For the manufacture of a medicament, a compound according to any one of (1) to (3) above, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof may be mixed with a pharmaceutically acceptable excipient, a diluent, a carrier, etc., and may be manufactured into a complex preparation together with other active agents to have a synergistic effect. [Form for carrying out the invention] Hereinafter, the present invention will be described in more detail through examples. These examples are only intended to explain the present invention more specifically, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. Example 1. Evaluation of antipruritic efficacy of the compound of the present invention The acute pruritus animal model, a standardized pruritus model, was used to confirm the acute pruritus inhibitory effect of compound 1 (N-(2-chloro-6-(4-chlorophenoxy)pyridin-4-yl)-4-(methylsulfonyl)-3,4-dihydro-2H-thieno[3,2-g]chromene-7-carboxamide) (Figs. 1 and 2). Specifically, the drug was used at 75 mg/kg of compound 1 prepared with excipients (10% DMSO, 20% PEG400, 10% Tween80, 60% 0.1 M NaHCO3 ) . As an animal model of acute pruritus, 9-week-old ICR female mice were used in the experiment after acclimatization for 1 week and stabilization. After anesthesia with an inhalation anesthetic 24 hours before the experiment, the nape area was cleanly shaven using clippers. Then, histamine and IL-31 were each injected intradermally to induce skin pruritus. The drugs were administered orally. Each experimental group is shown in Tables 1 and 2 below. [Table 1] Histamine-induced acute pruritus animal model No Group Administered substance Dose Administration volume Administration route N . (Inducer + drug) (mg/kg) (mL/kg) (Inducer + drug) (Number of individuals) 1 Normal group ( saline) Saline + vehicle - 10 Intradermal + oral 10 Control group Histamine + vehicle 2 (vehicle c - 10 Intradermal + oral 10 ) Experimental group Histamine + compound 3 (compoun 75 10 Intradermal + oral 10 d 1) Water 1 [Table 2] IL-31-induced acute pruritus animal model Administration N o. Group Administered substance Dose Administration route N ( Inducer + drug) Volume (mg/kg) (Inducer + drug) (Number of individuals) (mL/kg) 1 Normal group PBS ( PBS) + vehicle - 10 Intradermal + oral 10 2 Control group ( vehicle) IL-31+ vehicle - 10 intradermal + oral 10 Experimental group IL-31+ compound 3 (compound 1 75 10 intradermal + oral 10 1) Each animal was placed in an opaque acrylic cage, a video was recorded and played repeatedly, and the number of times the animal scratched using the hind legs was measured to evaluate the itch behavior. As a result, when compound 1 was administered, the number of scratching behaviors was reduced to 74.8% and 38.4% in the histamine-induced animal model and the IL-31-induced animal model, respectively, compared to the vehicle administration (Figs. 3 and 4). Example 2. Evaluation of the efficacy of the compound of the present invention in an atopic dermatitis animal model The effect of compound 1 on atopic dermatitis was confirmed using the EC (Epicutaneous) OVA sensitization animal model, which is an atopic dermatitis animal model (Fig. 5). Specifically, the drug was used at 75 mg/kg of compound 1 prepared with excipients (10% DMSO, 20% PEG400, 10% Tween80, 60% 0.1 M NaHCO3 ) . As an animal model of atopic dermatitis, 6-7 week old balb/c female mice were used in the experiment after acclimatization for 1 week and stabilization. After anesthesia with an inhalation anesthetic 24 hours before the experiment, the hair on the back was cleanly removed using clippers. After stimulating the back area 6 times with 3M tape, 200 μg of OVA in 100 μl of salin was applied to a sterile gauze 1.5 x 1.5 cm long and fixed with a sterile transparent film (Tegaderm TM ). Atopic dermatitis was induced by administering OVA stimulation twice a week (Day 0, 3, 21, 24, 42, 45) at 3-week intervals. The drug was administered orally daily during the OVA sensitization period, and the experiment was repeated twice. Each experimental group is shown in Tables 3 and 4 below. [Table 3] Atopic dermatitis animal model 1st experiment Administration N o. Group Administered substance Dose Administration route N ( Inducer + drug) Volume (mg/kg) (Inducer + drug) (Number of individuals) (mL/kg) 1 Normal group ( sham) Salin + vehicle - 10 Transdermal + oral 5 2 Control group ( vehicle) OVA + vehicle - 10 Transdermal + oral 5 Experimental group 3 (compound OVA + compound 1 75 10 Transdermal + oral 5 1) [Table 4] Atopic dermatitis animal model 2nd experiment N o. Group Administration Substance Administration Dose Administration Route N ( Inducer + Drug) Volume (mg/kg) (Inducer + Drug) (Number of Individuals) (mL/kg) 1 Normal group ( sham) Salin + Vehicle - 10 Percutaneous + Oral 4 2 Control group ( vehicle) OVA + Vehicle - 10 Percutaneous + Oral 6 Experimental group 3 (compound OVA + Compound 1 75 10 Percutaneous + Oral 4 1) For histopathological evaluation of mouse skin tissue, skin tissue was separated, fixed in paraffin, and changes in epidermal thickness were evaluated through hematoxylin-eosin (H&E) staining. was confirmed. In addition, RNA was isolated from skin tissue and the expression of cytokine genes related to inflammation was confirmed together through quantitative real-time PCR. In addition, each animal was placed in an opaque acrylic cage, a video was recorded for 1 hour, and the number of times the animal scratched using the hind legs was measured to evaluate the itch behavior. As a result of analyzing the back skin tissue through H&E staining, it was confirmed that the thickness of the epidermis tissue of the group administered 75 mg/kg of compound 1 was reduced by about 12.5% (1st, Figs. 6 and 7) and about 8.5% (2nd, Figs. 8 and 9) compared to the vehicle administration group. The number of scratching behaviors was significantly reduced by about 84.2% (1st, Fig. 10) and about 94.3% (2nd, Fig. 11) compared to the vehicle administration group. In addition, as a result of measuring gene expression in skin tissue, it was shown that the gene expression related to inflammation and itching was reduced in the compound 1 administration group compared to the vehicle administration group (Figs. 12 and 13). While specific parts of the present invention have been described in detail above, it will be obvious to those skilled in the art that such specific descriptions are only preferred embodiments and that the scope of the present invention is not limited thereby. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims

【청구의 범위】 【청구항 1】 하기 화학식 I로 표시되는 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물을 유효성분으로 포함하는, 아토피성 피부염 또는 가려움증의 예방 또는 치료용 약학적 조성물: [화학식 I]
Figure imgf000021_0001
상기 화학식 I에서, R1은 -S(=O)(=Ra)Rb이고, Ra는 =O 또는 =NH이고, Rb는 H, C1-6알킬, C1-6알콕시-C1-6알킬, C1-6알킬카보닐-C1-6알킬, C2-7알켄일, 아미노, 또는 아미노C1-6알킬이고, Rb의 적어도 하나의 H는 각각 독립적으로 F, Br, Cl 또는 I로 치환될 수 있으며; R2 및 R3는 각각 독립적으로 F, Br, Cl 또는 I이다. 【청구항 2】 제1항에 있어서, Ra는 =O이고, Rb는 치환되지 않은 C1-3알킬인, 아토피성 피부염 또는 가려움증의 예방 또는 치료용 약학적 조성물. 【청구항 3】 제1항에 있어서, 상기 화학식 I로 표시되는 화합물은 하기 화학식 II로 표시되는 것인, 아토피성 피부염 또는 가려움증의 예방 또는 치료용 약학적 조성물: [화학식 II] 【Scope of claims】 【Claim 1】 A pharmaceutical composition for preventing or treating atopic dermatitis or pruritus, comprising a compound represented by the following chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient: [Chemical formula I]
Figure imgf000021_0001
In the above chemical formula I, R 1 is -S(=O)(=R a )R b , R a is =O or =NH, R b is H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkylcarbonyl-C 1-6 alkyl, C 2-7 alkenyl, amino, or aminoC 1-6 alkyl, At least one H of R b may be independently substituted with F, Br, Cl or I; and R 2 and R 3 are each independently F, Br, Cl or I. 【Claim 2】 A pharmaceutical composition for preventing or treating atopic dermatitis or pruritus in claim 1, wherein R a is =O and R b is unsubstituted C 1-3 alkyl. 【Claim 3】 A pharmaceutical composition for preventing or treating atopic dermatitis or pruritus in claim 1, wherein the compound represented by the chemical formula I is represented by the following chemical formula II: [Chemical Formula II] . 【청구항 4】 제1항에 있어서, 상기 약학적 조성물은 IL-4, IL-5, IFN-γ, H4R, IL-17 및 IL-31로 이루어진 군에서 선택되는 하나 이상의 사이토카인의 발현을 감소시키는 것인, 아토피성 피부염 또는 가려움증의 예방 또는 치료용 약학적 조성물. 【청구항 5】 제1항에 있어서, 상기 약학적 조성물은 경구로 투여되는 것인, 아토피성 피부염 또는 가려움증의 예방 또는 치료용 약학적 조성물. 【청구항 6】 하기 화학식 I로 표시되는 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물을 이를 필요로 하는 개체에 투여하는 단계를 포함하는, 아토피성 피부염 또는 가려움증의 예방 또는 치료 방법: [화학식 I]
Figure imgf000024_0001
상기 화학식 I에서, R1은 -S(=O)(=Ra)Rb이고, Ra는 =O 또는 =NH이고, Rb는 H, C1-6알킬, C1-6알콕시-C1-6알킬, C1-6알킬카보닐-C1-6알킬, C2-7알켄일, 아미노, 또는 아미노C1-6알킬이고, Rb의 적어도 하나의 H는 각각 독립적으로 F, Br, Cl 또는 I로 치환될 수 있으며; R2 및 R3는 각각 독립적으로 F, Br, Cl 또는 I이다. 【청구항 7】 아토피성 피부염 또는 가려움증의 예방 또는 치료를 위한 하기 화학식 I로 표시되는 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물의 용도: [화학식 I]
Figure imgf000025_0001
상기 화학식 I에서, R1은 -S(=O)(=Ra)Rb이고, Ra는 =O 또는 =NH이고, Rb는 H, C1-6알킬, C1-6알콕시-C1-6알킬, C1-6알킬카보닐-C1-6알킬, C2-7알켄일, 아미노, 또는 아미노C1-6알킬이고, Rb의 적어도 하나의 H는 각각 독립적으로 F, Br, Cl 또는 I로 치환될 수 있으며; R2 및 R3는 각각 독립적으로 F, Br, Cl 또는 I이다. 【청구항 8】 아토피성 피부염 또는 가려움증의 예방 또는 치료용 약제의 제조를 위한 하기 화학식 I로 표시되는 화합물, 이의 입체 이성질체, 이의 약학적으로 허용 가능한 염, 이의 수화물 또는 이의 용매화물의 용도: [화학식 I]
Figure imgf000026_0001
상기 화학식 I에서, R1은 -S(=O)(=Ra)Rb이고, Ra는 =O 또는 =NH이고, Rb는 H, C1-6알킬, C1-6알콕시-C1-6알킬, C1-6알킬카보닐-C1-6알킬, C2-7알켄일, 아미노, 또는 아미노C1-6알킬이고, Rb의 적어도 하나의 H는 각각 독립적으로 F, Br, Cl 또는 I로 치환될 수 있으며; R2 및 R3는 각각 독립적으로 F, Br, Cl 또는 I이다. . 【Claim 4】 A pharmaceutical composition for preventing or treating atopic dermatitis or pruritus, wherein the pharmaceutical composition reduces the expression of one or more cytokines selected from the group consisting of IL-4, IL-5, IFN-γ, H4R, IL-17, and IL-31. 【Claim 5】 A pharmaceutical composition for preventing or treating atopic dermatitis or pruritus, wherein the pharmaceutical composition is administered orally. 【Claim 6】 A compound represented by the following chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof, to a subject in need thereof. Method for preventing or treating atopic dermatitis or pruritus, comprising the step of administering: [Chemical Formula I]
Figure imgf000024_0001
In the above chemical formula I, R 1 is -S(=O)(=R a )R b , R a is =O or =NH, R b is H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkylcarbonyl-C 1-6 alkyl, C 2-7 alkenyl, amino, or aminoC 1-6 alkyl, and at least one H of R b may be independently substituted with F, Br, Cl, or I; R 2 and R 3 are each independently F, Br, Cl, or I. 【Claim 7】 Use of a compound represented by the following chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof for the prevention or treatment of atopic dermatitis or pruritus: [Chemical formula I]
Figure imgf000025_0001
In the above chemical formula I, R 1 is -S(=O)(=R a )R b , R a is =O or =NH, R b is H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkylcarbonyl-C 1-6 alkyl, C 2-7 alkenyl, amino, or aminoC 1-6 alkyl, and at least one H of R b can be independently substituted with F, Br, Cl, or I; R 2 and R 3 are each independently F, Br, Cl or I. [Claim 8] Use of a compound represented by the following chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof for the manufacture of a drug for preventing or treating atopic dermatitis or pruritus: [Chemical formula I]
Figure imgf000026_0001
In the above chemical formula I, R 1 is -S(=O)(=R a )R b , R a is =O or =NH, and R b is H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkylcarbonyl-C 1-6 alkyl, C 2-7 alkenyl, Amino, or aminoC 1-6 alkyl, and at least one H of R b may be independently substituted with F, Br, Cl or I; R 2 and R 3 are each independently F, Br, Cl or I.
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014196793A1 (en) * 2013-06-05 2014-12-11 C&C Research Laboratories Heterocyclic derivatives and use thereof
US9556139B2 (en) * 2008-06-25 2017-01-31 Array Biopharma Inc. 6-substituted phenoxychroman carboxylic acid derivatives
KR20170081708A (en) * 2014-12-02 2017-07-12 주식회사 씨앤드씨신약연구소 Heterocyclic derivatives and use thereof
KR20230038125A (en) * 2021-09-10 2023-03-17 주식회사 프롬바이오 Heteroaryl derivatives as STAT3 inhibitor, and uses thereof
KR20230104086A (en) * 2021-10-27 2023-07-07 주식회사 휴켐바이오 Tricyclic derivative compounds and use thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9556139B2 (en) * 2008-06-25 2017-01-31 Array Biopharma Inc. 6-substituted phenoxychroman carboxylic acid derivatives
WO2014196793A1 (en) * 2013-06-05 2014-12-11 C&C Research Laboratories Heterocyclic derivatives and use thereof
KR20170081708A (en) * 2014-12-02 2017-07-12 주식회사 씨앤드씨신약연구소 Heterocyclic derivatives and use thereof
KR20230038125A (en) * 2021-09-10 2023-03-17 주식회사 프롬바이오 Heteroaryl derivatives as STAT3 inhibitor, and uses thereof
KR20230104086A (en) * 2021-10-27 2023-07-07 주식회사 휴켐바이오 Tricyclic derivative compounds and use thereof

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