[go: up one dir, main page]

WO2023068852A1 - Composé dérivé de benzothiophène-1,1-dioxyde utilisé en tant qu'inhibiteur de stat3 et son utilisation - Google Patents

Composé dérivé de benzothiophène-1,1-dioxyde utilisé en tant qu'inhibiteur de stat3 et son utilisation Download PDF

Info

Publication number
WO2023068852A1
WO2023068852A1 PCT/KR2022/016069 KR2022016069W WO2023068852A1 WO 2023068852 A1 WO2023068852 A1 WO 2023068852A1 KR 2022016069 W KR2022016069 W KR 2022016069W WO 2023068852 A1 WO2023068852 A1 WO 2023068852A1
Authority
WO
WIPO (PCT)
Prior art keywords
cancer
dioxidobenzo
thiophen
acetamide
acrylamide
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.)
Ceased
Application number
PCT/KR2022/016069
Other languages
English (en)
Korean (ko)
Inventor
심태진
김지훈
이준호
이민범
박영환
임재성
노준기
최누리
이혜원
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.)
Frombio Co Ltd
Original Assignee
Frombio Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Frombio Co Ltd filed Critical Frombio Co Ltd
Publication of WO2023068852A1 publication Critical patent/WO2023068852A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/64—Oxygen atoms
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • One object of the present invention is to provide a benzothiophene-1,1-dioxide derivative compound exhibiting STAT3 inhibitory activity and a method for preparing the same.
  • A is a 6-membered ring ⁇ wherein at least one H of the 6-membered ring is -H, -C 1-4 alkyl, -C 1-4 cyanoalkyl, -C 1-4 aminoalkyl, -C 1-4 hydroxyalkyl, -C 1-4 haloalkyl, -CN, -NR 1 R 2 , -OR 3 , halo, cycloalkyl, or heterocycloalkyl, or two adjacent substituents are linked together to form 6 can form a fused ring together with the original ring ⁇ ;
  • Y 1 and Y 2 are each independently -H, -C 1-4 alkyl, -NR 1 R 2 , -OR 3 , or halo;
  • Y 1 and Y 2 are each independently -H, -C 1-4 alkyl, or halo;
  • R A and R B are each independently -H or -C 1-4 alkyl
  • R 1 and R 2 are each independently -H or -C 1-4 alkyl
  • R 3 is -H, -C 1-4 alkyl, -C 1-4 haloalkyl, or -phenyl.
  • the compound represented by Formula 1 may be a compound represented by Formula 3 below:
  • Y 1 and Y 2 are each independently -H, -C 1-4 alkyl, -NR 1 R 2 , -OR 3 , or halo;
  • R 1 and R 2 are each independently -H or -C 1-4 alkyl
  • R 3 is -H, -C 1-4 alkyl, -C 1-4 haloalkyl, or -phenyl;
  • the compound represented by Formula 1 may be selected from the group consisting of the following compounds. However, it is not limited thereto.
  • alkyl may mean a straight-chain or branched-chain acyclic, cyclic, or saturated hydrocarbon in which they are bonded, unless otherwise specified.
  • C 1-4 alkyl may mean an alkyl containing 1 to 4 carbon atoms.
  • Non-cyclic alkyl may include, for example, methyl, ethyl, n -propyl, n -butyl, isopropyl, sec -butyl, isobutyl, or tert -butyl, etc. Not limited to this.
  • Cyclic alkyl may be used interchangeably with "cycloalkyl” herein, and may include, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, as examples. It doesn't work.
  • alkoxy can mean -(O-alkyl) as an alkyl ether group, where alkyl is as defined above.
  • C 1-4 alkoxy may mean C 1-4 alkyl-containing alkoxy, that is, -(OC 1-4 alkyl), and as an example, alkoxy is methoxy. ), ethoxy, n -propoxy, isopropoxy , n -butoxy, isobutoxy, sec - butoxy ), or tert -butoxy ( tert -butoxy), etc., but is not limited thereto.
  • halo can be F, Cl, Br, or I.
  • haloalkyl can mean a straight or branched chain alkyl (hydrocarbon) having carbon atoms substituted with one or more halo as defined herein.
  • haloalkyl include, but are not limited to, methyl, ethyl, propyl, isopropyl, isobutyl or n -butyl independently substituted with one or more halogens such as F, Cl, Br, or I .
  • aminoalkyl may mean a straight-chain or branched-chain alkyl (hydrocarbon) having a carbon atom substituted with amino (NR'R").
  • R' and R" are each independently hydrogen , And C 1-4 It may be selected from the group consisting of alkyl, and the selected R' and R" may each independently be substituted or unsubstituted.
  • hydroxyalkyl may mean a straight-chain or branched-chain alkyl (hydrocarbon) having a carbon atom substituted with hydroxy (OH).
  • cyanoalkyl may mean a straight-chain or branched-chain alkyl (hydrocarbon) having a carbon atom substituted with cyano (CN).
  • heterocycloalkyl may mean a ring containing 1 to 5 heteroatoms selected from N, O and S as atoms forming the ring, and may be saturated or partially unsaturated.
  • unsaturated it may be referred to as a heterocycloalkene.
  • a heterocycloalkyl can be a single ring or multiple rings such as spiro rings, bridged rings or fused rings.
  • heterocycloalkyl may mean a heterocycloalkyl containing 3 to 12 atoms forming a ring
  • heterocycloalkyl includes pyrrolidine, piperidine, Dazolidine, pyrazolidine, butyrolactam, valerolactam, imidazolidinone, hydantoin, dioxolane, phthalimide, piperidine, pyrimidine-2,4( 1H , 3H )- Dione, 1,4-dioxane, morpholine, thiomorpholine, thiomorpholine- S -oxide, thiomorpholine- S , S -oxide, piperazine, pyran, pyridone, 3-pyrroline, Thiophyran, pyrone, tetrahydrofuran, tetrahydrothiophene, quinuclidine, tropane, 2-azaspiro[3.3]hept
  • arene may mean an aromatic hydrocarbon ring.
  • Arenes can be monocyclic arenes or polycyclic arenes.
  • the number of ring carbon atoms of the arene may be 5 or more and 30 or less, 5 or more and 20 or less, or 5 or more and 15 or less.
  • examples of arenes include benzene, naphthalene, fluorene, anthracene, phenanthrene, terbenzene, quarterbenzene, quincbenzene, sexybenzene, triphenylene, pyrene, benzofluoranthene, chrysene, and the like. Not limited.
  • aryl a residue obtained by removing one hydrogen atom from the above "arene" is referred to as "aryl".
  • heteroene may be an aromatic ring containing one or more of O, N, P, Si, and S as heterogeneous elements.
  • the number of ring carbon atoms of the heteroarene may be 2 or more and 30 or less, or 2 or more and 20 or less.
  • Heteroarenes may be monocyclic heteroarenes or polycyclic heteroarenes.
  • Polycyclic heteroarenes may have, for example, a bicyclic or tricyclic structure.
  • heteroarenes examples include thiophene, purine, pyrrole, pyrazole, imidazole, thiazole, oxazole, isothiazole, oxadiazole, triazole, pyridine, triazine, acridyl, pyridazine, pyrazine, and quinoline.
  • the term "enantiomer” means a compound of the present invention or a salt thereof having the same chemical formula or molecular formula but sterically different. Each of these optical isomers and mixtures thereof are also included in the scope of the present invention.
  • the solid bond (-) connecting an asymmetric carbon atom is a wedge-shaped solid bond representing the absolute configuration of the stereogenic center. or Wedge Dotted Combination can include
  • the compound of Formula 1 of the present invention may exist in the form of a "pharmaceutically acceptable salt".
  • a pharmaceutically acceptable free acid is useful.
  • pharmaceutically acceptable salt is a concentration that has a relatively non-toxic and harmless effective effect on patients, and any of the compounds represented by Formula 1 do not reduce the beneficial effects of the compound represented by Formula 1 by side effects caused by the salt. means any organic acid or inorganic acid addition salt of
  • Acid addition salts are prepared by conventional methods, for example, by dissolving a compound in an excess aqueous acid solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. Equimolar amounts of the compound and acid or alcohol in water may be heated, and then the mixture may be evaporated to dryness, or the precipitated salt may be suction filtered.
  • a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile.
  • organic acids and inorganic acids may be used as the free acid, hydrochloric acid, phosphoric acid, sulfuric acid, or nitric acid may be used as the inorganic acid, and methanesulfonic acid, p -toluenesulfonic acid, acetic acid, trifluoroacetic acid, Maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, glue Conic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, or hydroiodic acid, etc. can be used. However, it is not limited to these.
  • a pharmaceutically acceptable metal salt may be prepared using a base.
  • the alkali metal salt or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate.
  • the metal salt it is particularly suitable for preparing a sodium, potassium, or calcium salt, but is not limited thereto.
  • the corresponding silver salt can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).
  • Pharmaceutically acceptable salts of the present invention include salts of acidic or basic groups that may be present in the compounds of Formula 1 above.
  • pharmaceutically acceptable salts may include sodium, calcium and potassium salts of a hydroxyl group
  • other pharmaceutically acceptable salts of an amino group include hydrobromides, sulfates, hydrogen sulfates, phosphates, hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate), and p -toluenesulfonate (tosylate) salts; It can be prepared through a method for preparing a salt known to.
  • the present invention provides a use of a compound represented by Formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.
  • the compound represented by Formula 1 of the present invention exhibits inhibitory activity against STAT3, treatment of STAT3-related diseases, particularly cancer, fibrotic diseases, or autoimmune diseases Or it can be useful for prevention.
  • STAT3 is known to be involved in cancer, fibrotic disease, or autoimmune disease by acting as a transcription factor and regulating the expression of various genes, inhibiting STAT3 activity prevents cancer, fibrotic disease, inflammatory disease, or autoimmune disease or can be treated.
  • the cancer includes all "cancers” that can exhibit therapeutic or preventive effects due to inhibition of STAT3 activity, and may be solid cancers or hematological cancers.
  • cancers may be solid cancers or hematological cancers.
  • pseudomyxoma intrahepatic cholangiocarcinoma, hepatoblastoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, lip cancer, mycosis fungoides, acute myelogenous leukemia, acute lymphocytic leukemia, basal cell carcinoma, ovarian Epithelial cancer, ovarian germ cell cancer, male breast cancer, brain cancer, pituitary adenoma, multiple myeloma, gallbladder cancer, biliary tract cancer, colorectal cancer, head and neck cancer, chronic myelogenous leukemia, chronic lymphocytic leukemia, retinoblastoma, choroidal
  • the fibrotic disease refers to any disease caused by fibrosis or inflammation and damage caused by an inducing substance, and liver fibrosis (eg, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH)) ), pulmonary fibrosis, diabetic fibrosis, cardiac fibrosis, renal fibrosis, scleroderma, skeletal muscle fibrosis, intestinal fibrosis, pancreatic fibrosis, articular fibrosis, myelofibrosis, myocardial fibrosis, dermal fibrosis, elastic fibrosis, retroperitoneal fibrosis, cystic fibrosis, uterine fibrosis , And may be one or more selected from the group consisting of cellular fibrosis, but is not limited thereto.
  • liver fibrosis eg, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH)
  • the inflammatory disease or autoimmune disease refers to any disease caused by direct or indirect causes of an immune response to a diseased subject's own antigen, and includes psoriasis, atopic dermatitis, pneumonia, lymphadenitis, rheumatoid arthritis, and immune thrombocytopenia.
  • the pharmaceutical composition of the present invention may further contain at least one active ingredient in addition to the compound represented by Formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.
  • the step of administering a therapeutically effective amount of the compound represented by Formula 1, its optical isomer, or its pharmaceutically acceptable salt to a subject in need thereof It provides a method for treating or preventing a STAT3-related disease, particularly cancer, fibrotic disease, or autoimmune disease, including.
  • the subject may be a mammal including a human.
  • therapeutically effective amount used in the present invention refers to an amount of the compound represented by Formula 1 effective for the treatment or prevention of STAT3-related diseases.
  • therapeutically effective amount means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type and severity of the subject, age, sex, type of disease, It may be determined according to the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of excretion, the duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field.
  • the pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, or may be administered sequentially or simultaneously with a commercially available therapeutic agent. And it can be single or multiple administrations. It is important to administer the amount that can obtain the maximum effect with the minimum amount without side effects in consideration of all the above factors, and can be easily determined by those skilled in the art.
  • the dosage of the pharmaceutical composition of the present invention may be determined by an expert according to various factors such as the patient's condition, age, sex, and complications. Since the active ingredient of the pharmaceutical composition of the present invention is excellent in safety, it can be used even at a dose determined or higher.
  • the present invention is a compound represented by Formula 1, an optical isomer thereof, or a pharmaceutical thereof for use in the preparation of a medicament for use in the treatment or prevention of STAT3-related diseases
  • Uses of the generally acceptable salts are provided.
  • the compound represented by Formula 1 for the preparation of a drug may be mixed with an acceptable adjuvant, diluent, carrier, etc., and may be prepared as a combined preparation with other active agents to have a synergistic action of the active ingredients.
  • Embodiments of the present invention may be modified in various other forms, and the scope of the present invention is not limited to the embodiments described below.
  • embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.
  • "include” a certain component throughout the specification means that other components may be further included without excluding other components unless otherwise stated.
  • novel benzothiophene-1,1-dioxide derivative compounds of the present invention bind to the SH2 domain of STAT3 and show excellent STAT3-selective inhibitory activity, they can be very useful for preventing or treating STAT3-related diseases.
  • Figure 1 shows the effect of inhibiting the transcriptional activity of STAT3 induced by IL-6 of Example compounds.
  • Step 1a Preparation of Compound S1
  • step 1 The reaction of step 1 was carried out according to Scheme 1 and recrystallized from CH 2 Cl 2 / n -hexane (1:20) to obtain the title compound as a pale yellow solid (173.0 mg, 87%).
  • Example 22 N-(1,1-dioxidobenzo[ b ]thiophen-6-yl)-2-(4-fluorophenyl)acrylamide ⁇ N-(1,1-Dioxidobenzo[ b Preparation of ]thiophen-6-yl)-2-(4-fluorophenyl)acrylamide ⁇
  • Example 28 2-(2,4-dichlorophenyl)-N-(1,1-dioxidobenzo[ b ]thiophen-6-yl)acrylamide ⁇ 2-(2,4-dichlorophenyl)-N-(1,1-dioxidobenzo[ b Preparation of ]thiophen-6-yl)acrylamide ⁇
  • Example 33 N-(1,1-dioxidobenzo[ b ]thiophen-6-yl)-2-(3,4,5-trimethoxyphenyl)acrylamide ⁇ N-(1,1-dioxidobenzo[ b Preparation of ]thiophen-6-yl)-2-(3,4,5-trimethoxyphenyl)acetamide ⁇
  • Example 37 2-(3,5-difluorophenyl)-N-(1,1-dioxidobenzo[ b ]thiophen-6-yl)acetamide ⁇ 2-(3,5-difluorophenyl)-N-(1,1-dioxidobenzo[ b Preparation of ]thiophen-6-yl)acetamide ⁇
  • step 1 The reaction of step 1 was carried out according to Scheme 1 and purified by recrystallization with EtOAc and n -hexane to obtain the title compound as a yellow solid (359.6 mg, 97%).
  • Example 38 N-(1,1-dioxidobenzo[ b ]thiophen-6-yl)-2-(2-fluorophenyl)acetamide ⁇ N-(1,1-dioxidobenzo[ b Preparation of ]thiophen-6-yl)-2-(2-fluorophenyl)acetamide ⁇
  • Example 39 2-(2,3-dihydrobenzo[ b ][1,4]dioxin-6-yl)-N-(1,1-dioxidobenzo[ b ]thiophene-6-yl)acetamide ⁇ 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-(1,1-dioxidobenzo[ b Preparation of ]thiophen-6-yl)acetamide ⁇
  • step 1 The reaction of step 1 was carried out according to Scheme 1 and purified by recrystallization with MeOH to obtain the title compound as a pale yellow solid (113.4 mg, 29%).
  • Example 40 2-(3,4-dimethylphenyl)-N-(1,1-dioxidobenzo[ b ]thiophen-6-yl)acetamide ⁇ 2-(3,4-dimethylphenyl)-N-(1,1-dioxidobenzo[ b Preparation of ]thiophen-6-yl)acetamide ⁇
  • Example 41 2-(3,5-difluorophenyl)-N-(1,1-dioxidobenzo[ b ]thiophen-6-yl)acrylamide ⁇ 2-(3,5-difluorophenyl)-N-(1,1-dioxidobenzo[ b Preparation of ]thiophen-6-yl)acrylamide ⁇
  • Example 42 N-(1,1-dioxidobenzo[ b ]thiophen-6-yl)-2-(2-fluorophenyl)acrylamide ⁇ N-(1,1-dioxidobenzo[ b Preparation of ]thiophen-6-yl)-2-(2-fluorophenyl)acrylamide ⁇
  • Stat3 Luciferase Reporter HEK293 Stable Cell Line (Cat# SL-0071-NP) containing the STAT3 reporter gene was purchased from Signosis and 10% FBS (Thermo fisher scientific, Cat# 26140-079), It was cultured in DMEM High Glucose (Thermo fisher scientific, Cat# 11995-073) medium supplemented with 1% penicillin/streptomycin (Thermo fisher scientific, Cat# 15140-122), and hygromycin was added at 100 ⁇ g/ml By treatment with a concentration of luciferase (luciferase) to obtain a stable expression clone (clone).
  • FBS Thermo fisher scientific, Cat# 26140-079
  • DMEM High Glucose Thermo fisher scientific, Cat# 11995-073
  • penicillin/streptomycin Thermo fisher scientific, Cat# 15140-122
  • hygromycin was added at 100

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un composé dérivé de benzothiophène-1,1-dioxyde ayant une activité inhibitrice de STAT3 et son utilisation. Les composés dérivés de benzothiophène-1,1-dioxyde selon la présente invention se lient à des domaines SH2 de STAT3 et présentent d'excellentes activités inhibitrices sélectives de STAT3, et peuvent ainsi être très utiles pour prévenir ou traiter des maladies liées à STAT3.
PCT/KR2022/016069 2021-10-20 2022-10-20 Composé dérivé de benzothiophène-1,1-dioxyde utilisé en tant qu'inhibiteur de stat3 et son utilisation Ceased WO2023068852A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR20210140286 2021-10-20
KR10-2021-0140286 2021-10-20

Publications (1)

Publication Number Publication Date
WO2023068852A1 true WO2023068852A1 (fr) 2023-04-27

Family

ID=86059542

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2022/016069 Ceased WO2023068852A1 (fr) 2021-10-20 2022-10-20 Composé dérivé de benzothiophène-1,1-dioxyde utilisé en tant qu'inhibiteur de stat3 et son utilisation

Country Status (2)

Country Link
KR (1) KR20230056618A (fr)
WO (1) WO2023068852A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150361031A1 (en) * 2013-01-15 2015-12-17 Board Of Regents, The University Of Texas System Stat3 inhibitor

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150361031A1 (en) * 2013-01-15 2015-12-17 Board Of Regents, The University Of Texas System Stat3 inhibitor

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEN HAIJUN, YANG ZHENGDUO, DING CHUNYONG, CHU LILI, ZHANG YUSONG, TERRY KRISTIN, LIU HUILING, SHEN QIANG, ZHOU JIA: "Fragment-based drug design and identification of HJC0123 , a novel orally bioavailable STAT3 inhibitor for cancer therapy", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 62, 1 April 2013 (2013-04-01), AMSTERDAM, NL , pages 498 - 507, XP093059891, ISSN: 0223-5234, DOI: 10.1016/j.ejmech.2013.01.023 *
DATABASE Registry CAS; 17 July 2013 (2013-07-17), ANONYMOUS : "Benzeneacetamide, N-(1, 1-dioxidobenzo[b]th ien-6-yl)-2,5-difluoro - ", XP093059884, Database accession no. 1445121-08-3 *
HUANG QIUYAO, ZHONG YAN, LI BINGBING, OUYANG SHUMIN, DENG LIN, MO JIANSHAN, SHI SHUO, LV NAN, WU RUIBO, LIU PEIQING, HU WENHAO, ZH: "Structure-based discovery of potent and selective small-molecule inhibitors targeting signal transducer and activator of transcription 3 (STAT3)", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 221, 1 October 2021 (2021-10-01), AMSTERDAM, NL , pages 113525, XP093059886, ISSN: 0223-5234, DOI: 10.1016/j.ejmech.2021.113525 *
LI WEN‐ZHEN, XI HUI‐ZHI, WANG YI‐JIE, MA HONG‐BO, CHENG ZHI‐QIANG, YANG YU, WU MENG‐LING, LIU TING‐MEI, YANG WEN, WANG QIN, LIAO M: "Design, synthesis, and biological evaluation of benzo[b]thiophene 1,1‐dioxide derivatives as potent STAT3 inhibitors", CHEMICAL BIOLOGY & DRUG DESIGN, vol. 98, no. 5, 1 November 2021 (2021-11-01), Hoboken, USA, pages 835 - 849, XP093059888, ISSN: 1747-0277, DOI: 10.1111/cbdd.13939 *

Also Published As

Publication number Publication date
KR20230056618A (ko) 2023-04-27

Similar Documents

Publication Publication Date Title
WO2016200101A2 (fr) Composé dérivé tricyclique, son procédé de préparation, et composition pharmaceutique le contenant
WO2019112344A1 (fr) Nouveau dérivé de pyrimidine ayant pour effet d'inhiber la croissance de cellules cancéreuses, et composition pharmaceutique contenant celui-ci
WO2017142325A1 (fr) Nouveau composé thiophène substitué en 2,3,5 utilisé en tant qu'inhibiteur de la protéine kinase
WO2021107656A2 (fr) Nouveau dérivé d'oxydo-réduction de la quercétine et son utilisation en tant qu'inhibiteur de bet
WO2015160192A1 (fr) Composition pharmaceutique permettant de traiter et de prévenir la leucémie, contenant un dérivé de thiénopyrimidine ou un sel pharmaceutiquement acceptable de celui-ci
WO2018004258A1 (fr) Nouveau dérivé hétérocyclique et son utilisation
WO2021029632A1 (fr) Composés hétéroaryle à cycles condensés utilisés en tant qu'inhibiteurs de ripk1
WO2016032209A2 (fr) N-(pyrrolidin-3-yl)-7h-pyrrolo[2,3-d]pyrimidine-4-amine substituée utilisée en tant qu'inhibiteur de la janus kinase
WO2011049274A1 (fr) Dérivés d'imidazole et compositions pour le traitement d'un mélanome
WO2023038481A1 (fr) Composé de dérivé hétéroarylique en tant qu'inhibiteur de stat3 et utilisation associée
WO2023068852A1 (fr) Composé dérivé de benzothiophène-1,1-dioxyde utilisé en tant qu'inhibiteur de stat3 et son utilisation
WO2023239165A1 (fr) Dérivés de phénylsulfonamide, leur procédé de préparation et composition pharmaceutique pour la prévention ou le traitement du cancer les contenant en tant que principe actif
WO2024005516A1 (fr) Composé dérivé d'hétéroaryle et son utilisation
WO2017115914A1 (fr) Inhibiteur de la phosphorylation de ppary et composition pharmaceutique le comprenant
WO2022103149A1 (fr) Nouveau dérivé de carbazole et composition pharmaceutique pour la prévention ou le traitement du cancer le comprenant en tant que principe actif
WO2017164705A1 (fr) Nouveau dérivé de pyridine, son procédé de préparation, et composition pharmaceutique pour prévenir ou traiter une maladie liée à fgfr contenant ledit dérivé comme principe actif
WO2021235813A1 (fr) Composition pharmaceutique pour la prévention ou le traitement du cancer du pancréas associé à une mutation ron et méthode l'utilisant
WO2021040422A1 (fr) Nouveau dérivé de pyrimido[4,5-d]pyrimidine-2-one ayant une activité inhibitrice de protéine kinase
AU2020211253A1 (en) A fused ring heteroaryl compound as an ALK4/5 inhibitor
WO2020190073A1 (fr) Composition pharmaceutique comprenant un nouveau composé hétérocyclique azolopyrimidine en tant que principe actif
WO2019235894A1 (fr) Composition pour la prévention ou le traitement du cancer solide comprenant un composé inhibant la liaison de aimp2-dx2 et de k-ras et nouveau composé inhibant la liaison de aimp2-dx2 et k-ras
WO2025080100A1 (fr) Nouveau composé di-amide, son procédé de préparation et composition pharmaceutique pour la prévention ou le traitement du cancer ou de maladies auto-immunes le comprenant en tant que principe actif
WO2025034034A1 (fr) Nouveau composé et composition pharmaceutique pour prévenir ou traiter le cancer ou des tumeurs le comprenant
WO2018004290A1 (fr) Nouveau dérivé de pyrazole en tant qu'inhibiteur d'alk5 et ses utilisations
WO2025063725A1 (fr) Nouveau dérivé squelettique efficace pour la mutation de her2 et composition pharmaceutique le comprenant

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22884074

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 05/08/2024)

122 Ep: pct application non-entry in european phase

Ref document number: 22884074

Country of ref document: EP

Kind code of ref document: A1