WO2015050379A1 - Nouveau dérivé de quinolinone et son utilisation - Google Patents

Nouveau dérivé de quinolinone et son utilisation Download PDF

Info

Publication number
WO2015050379A1
WO2015050379A1 PCT/KR2014/009272 KR2014009272W WO2015050379A1 WO 2015050379 A1 WO2015050379 A1 WO 2015050379A1 KR 2014009272 W KR2014009272 W KR 2014009272W WO 2015050379 A1 WO2015050379 A1 WO 2015050379A1
Authority
WO
WIPO (PCT)
Prior art keywords
oxo
carboxamide
dihydroquinoline
ethyl
methyl
Prior art date
Application number
PCT/KR2014/009272
Other languages
English (en)
Korean (ko)
Inventor
김용철
고효진
곽승화
김민정
이소덕
Original Assignee
광주과학기술원
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 광주과학기술원 filed Critical 광주과학기술원
Priority to KR1020167008791A priority Critical patent/KR101731102B1/ko
Publication of WO2015050379A1 publication Critical patent/WO2015050379A1/fr

Links

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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D409/06—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 carbon chain containing only aliphatic carbon atoms

Definitions

  • the present invention relates to novel quinolinone derivatives and their preventive and therapeutic uses for diseases associated with excessive IL-2 activity.
  • Interleukin-2 also called T-cel growth factor, plays an important role in T-cell dependent immune response.
  • IL-2 is ⁇ eojin which the 15kDa in size with four bundled with helical protein is produced and secreted by ⁇ cells: not only involved in the proliferation and activation of ⁇ cell differentiation, and other like ⁇ cells and macrophages It is an important cytokine that also affects the activation of immune cells.
  • IL-2 binds to high-affinity receptors consisting of IL-2R a (CD25), IL-2RP (CD122) and IL-2R ⁇ (CD132) subunits of target cell membranes, of which both IL-2RP and IL-2R Y plays an important role in intracellular signaling, and IL-2R a has a short intracellular domain that is not involved in signaling but increases receptor affinity by 10-100 fold.
  • Gene expression encoding IL ⁇ 2 is regulated by electronic regulators such as NF-AT, AP-1, NF- ⁇ ⁇ and Oct, which are rarely expressed in normal, but rapidly when the immune system is activated. However, expression is induced for a limited time so that the protein is synthesized and secreted.
  • the inventors of the present invention sought extensive research to develop compositions for the prevention or treatment of various' inflammatory diseases and autoimmune diseases by discovering effective antagonists of inflammatory cytokines IL-2, which play an important role in the development of immunomodulatory diseases. As a result, the present invention has been completed by discovering that the novel quinolinone derivatives of the present invention inhibit the activity of IL-2 very effectively.
  • Another object of the present invention to provide a composition for inhibiting the activity of IL-2 (Inter leukin-2).
  • Still another object of the present invention is to provide a composition for preventing or treating an inflammatory disease or an autoimmune disease.
  • the invention is represented by the following formula (1) Quinolinone (qui no 1 inone) provides pharmaceutically acceptable salts thereof:
  • Ri, 3 ⁇ 4 and 3 ⁇ 4 are each independently hydrogen, nitro,
  • m is an integer from 0-2) or CrCs alkyl; Cr? Alkoxy; Unsubstituted or C r C 3 alkoxy, dC 5 alkyl, hydroxy, halogen, nitro, NH 2, formyl, cyano, CrCs alkylthio, phenoxy, phenylthio, phenyl-dC 3 alkyl, or substituted pyrazolo Phenyl; Furan; Thiophene; Blood; C 5 -C 6 cycloalkyl; Dihydroindene unsubstituted or substituted with ( ⁇ ): 5 alkyl, d-Cs alkoxy, halogen, nitro, hydroxy, d-Cs alkylthio or -NH 2 ; or diphenylmethyl; and q are each independently an integer from 0-2); R 5 is hydrogen, d—Cs alkoxy dC 3 alkyl, —NA 4 A 5 (A 4 ′ and A 5 are each
  • the present inventors made diligent research efforts to develop a composition for preventing or treating various inflammatory diseases and autoimmune diseases by discovering an effective antagonist of inflammatory cytokine IL ⁇ 2 which plays an important role in the development of immunomodulatory related diseases.
  • the novel quinolinone derivative represented by Chemical Formula 1 was found to effectively inhibit the activity of IL-2.
  • alkyl refers to a straight or branched saturated hydrocarbon group, and includes, for example, methyl, ethyl propyl, isobutyl or pentyl and the like.
  • CPC 5 alkyl means an alkyl group having an alkyl unit having 1 to 5 carbon atoms, and when dC 5 alkyl is substituted, the carbon number of the substituent is not included.
  • dC 5 alkyl is specifically dC 3 alkyl.
  • halogen refers to a halogen group element and includes, for example, fluoro, chloro, bromo and iodo.
  • alkenyl refers to an unsaturated hydrocarbon group including a double bond, and when C 2 -C 5 alkenyl is substituted, carbon number of the substituent is not included. .
  • alkoxy refers to a radical formed by the removal of hydrogen from an alcohol, where dC 3 alkoxy is substituted, the carbon number of the substituent is It is not included.
  • aryl refers to a substituted or unsubstituted monocyclic or polycyclic carbon ring which is wholly or partially unsaturated and has aromatic (aromat i c i ty).
  • alkylthio means a radical formed by removing hydrogen from thio (thio 1), and when C-C 5 alkylthio is substituted, the carbon number of the substituent is not included.
  • arylalkyl refers to alkyl substituted with an aryl group.
  • Aryl (: 4 ( alkyl) means an alkyl unit having 1 to 4 carbon atoms substituted with an aryl group.
  • phenylthio refers to a radical formed by the removal of hydrogen from thiophenol (thiophenol).
  • the quinolinone derivatives of the present invention may be used in the form of pharmaceutically acceptable salts, and as salts, acid addition salts formed by pharmaceutically acceptable free acids may be used.
  • Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid, aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes.
  • Acid addition salts according to the present invention are conventional methods, for example, a warfare product formed by dissolving a derivative of Formula 1 in an organic solvent, for example methane, ethanol, acetone, methylene chloride, acetonitrile, and adding an organic or inorganic acid.
  • an organic solvent for example methane, ethanol, acetone, methylene chloride, acetonitrile, and adding an organic or inorganic acid.
  • the solvent may be prepared by filtration, drying, or by distillation under reduced pressure of the solvent and excess acid, followed by drying or crystallization under an organic solvent.
  • Bases can also be used to make pharmaceutically acceptable metal salts.
  • Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving the compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare sodium, potassium or calcium salt as the metal salt.
  • Corresponding silver salts are also obtained by reacting an alkali or alkaline earth metal salt with a suitable negative salt (eg silver nitrate).
  • the present invention includes not only the quinolinone derivative represented by Formula 1 and a pharmaceutically acceptable salt thereof, but also possible solvates, hydrates, stereoisomers, and the like that can be prepared therefrom. According to a specific embodiment of the invention, the formula 1 of the present invention.
  • R 2 and 3 ⁇ 4 are each independently hydrogen, nitro, halogen, -N3 ⁇ 4, hydrazino or (Phenyl unsubstituted or substituted with dC 3 alkyl, halogen, C 2 -C 3 alkenyl, nitro, hydroxy, hydroxy dC 3 alkyl, d—C 3 alkoxy or phenyl; naphthalyl; unsubstituted or halogen, DC 3 alkyl substituted with nitro, C 2 _C 3 alkenyl; c 5 -c 6 cycloalkyl; adamantane, unsubstituted or substituted with halogen or methyl; Ci-C 3 alkoxy; CrCs alkylthio; or benzodioxol N is 0-2 Is an integer).
  • R4 of formula 1 of the present invention is hydrogen, dC 3 alkyl, c (A 2 is unsubstituted or halogen, dC 3 alkyl, C ⁇ C 3 alkoxy, nitro, —N3 ⁇ 4, dC 3 Phenyl substituted with alkylthio, phenyl, phenyl (: ⁇ (: 3 alkyl, phenoxy, cyano, hydroxy, hydroxy CrC 3 alkyl, formyl, phenylthio or pyrazole; naphthalyl; cyclopentadiene; blood Furan; thiophene; C 5 -C 6 cycloalkyl; unsubstituted or d—C 3 alkyl, dC 3 alkoxy, halogen, nitro, cyano hydroxy, formyl, C ⁇ C 3 alkylthio or —NH 2 ; Substituted dihydroindene;
  • 3 ⁇ 4 of formula 1 of the present invention is hydrogen, d-Cs alkoxy C ⁇ C 2 alkyl, -NA 4 A 5 (A 4 and A 5 are each independently hydrogen; unsubstituted or phenyl , dihydro-indene, naphthyl talril, dC dC 3 3 alkoxy or alkyl, dC 3 alkyl substituted by alkylthio; unsubstituted or dC 3 alkyl, halogen, hydroxy dC 3 alkyl, C 2 -C 3 alkenyl, sulfonamide, Phenyl substituted with CrC 3 alkoxy, hydroxy or nitro) or [A 6 is dC 3 alkoxy, halogen hydroxy, c ⁇ C 2 alkylthio or —NA 7 A 8 (A 7 and A 8 are each independently hydrogen; unsubstituted or substituted with phenyl, nitro,
  • the present invention is a composition for inhibiting the activity of IL-2 (Int er eukin-2) comprising a quinolinone derivative disclosed in the present invention or a pharmaceutically acceptable salt thereof as an active ingredient To provide.
  • IL-2 Int er eukin-2
  • the present invention provides a prophylactic method for preventing a disease associated with IL-2 overexpression or IL-2 overactivity comprising a quinolinone derivative disclosed herein or a pharmaceutically acceptable salt thereof as an active ingredient. Or a therapeutic composition.
  • the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier.
  • Pharmaceutically acceptable carriers contained in the pharmaceutical composition of the present invention are those commonly used in the preparation, lactose, textose, sucrose, sorbbi, manny, starch, acacia rubber, phosphate, alginate, Gelatin Calcium Silicate, Microcrystalline Cellulose, Polyvinylpyridone, Cellulose, Water, Syrup, Methyl Cellulose, Methylhydroxybenzoate, Propylhydroxybenzoate, Talc, Magnesium Stearate and Mineral Oil One is not limited thereto.
  • the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like, in addition to the above components.
  • a lubricant e.g., talc, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, mannitol, mannitol, mannitol, mannitol, mannitol, mannitol, mannitol, mannitol, mann
  • the pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, or the like.
  • Suitable dosages of the pharmaceutical compositions of the present invention may be prescribed in various ways depending on factors such as the method of formulation, the mode of administration, the age of the patient, body weight, sex, morbidity, food, time of administration, route of excretion and response sensitivity. Can be.
  • the daily dose of the pharmaceutical composition of the present invention is, for example, 0.001-100 mg / kg.
  • the pharmaceutical compositions of the present invention may be prepared in unit dose form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Or may be prepared by incorporation into a multi-dose container.
  • the formulation may be in the form of solutions, suspensions, syrups or emulsions in oil or aqueous media, or may be in the form of axes, powders, powders, granules, tablets or accelerators, and may further comprise dispersants or stabilizers.
  • the disease associated with IL-2 overexpression or IL-2 overactivity treated with the composition of the invention is an inflammatory disease or an autoimmune disease.
  • the inflammatory disease is chronic obstructive pulmonary disease (chroni c obstructive pulmonary disease, airways hyper- responsiveness, septic shock, glomerulonephritis, inflammatory bowel disease, Crohn's disease, ulcerat ive colitis, atherosclerosis And myoblastic leukaemia, diabetes, burns, ischemic heart disease, stroke, meningitis and varicose veins.
  • the autoimmune disease is a disease selected from the group consisting of rheumatoid arthritis, psoriasis, allergic dermatitis, multiple sclerosis, lupus and asthma.
  • the present invention provides a method for treating an inflammatory disease or an autoimmune disease comprising administering to a subject a composition comprising a quinolinone derivative of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient.
  • a composition comprising a quinolinone derivative of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the quinolinone derivative compounds used in the present invention and the inflammatory diseases or autoimmune diseases that can be prevented or treated with the compositions of the present invention have already been described above, and the description thereof is omitted to avoid excessive redundancy.
  • the present invention provides various novel quinolinone derivative compounds and compositions for inhibiting IL-2 activity comprising them as active ingredients.
  • the present invention can be usefully used for the prevention or treatment of various diseases associated with excessive expression or activity of IL-2, namely chronic inflammatory disease, inflammatory pain or autoimmune disease.
  • Quinolinone is a natural product derived from plants and is known to have various biological activities.
  • quinolinone has a chemical structure and shows the possibility of hydrogen bonding to the lactam moiety contained therein. Based on these facts, a large amount of quinolinone compounds was efficiently synthesized to investigate the biological activity of quinolinones.
  • IL-2 ELISA analysis explored the potential as an immunosuppressant in Jurkat T cells and confirmed that certain substances have a high potential as immunosuppressants.
  • IL-2 is produced primarily in T cells but also in killer (NK) cells.
  • T cell NK cells cytokine networks.
  • IL-2 gene knockout mice are known to develop inflammatory bowel disease and hemolytic anemia. It is also known to increase the production of IgGl, IgE, and IL-2 plays an important role in maintaining the balance of T H 1 / T H 2.

Abstract

La présente invention concerne: divers nouveaux composés de dérivés de quinolinone; et une composition pour l'inhibition de l'activité d'IL-2, contenant lesdits composés en tant que principe actif. La présente invention peut être utile pour la prévention ou le traitement de diverses maladies associées à l'expression/l'activité excessive d'IL-2, c'est -à-dire, des maladies inflammatoires ou des maladies auto-immunes chroniques.
PCT/KR2014/009272 2013-10-01 2014-10-01 Nouveau dérivé de quinolinone et son utilisation WO2015050379A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1020167008791A KR101731102B1 (ko) 2013-10-01 2014-10-01 신규한 퀴놀리논 유도체 및 이의 용도

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2013-0117515 2013-10-01
KR20130117515 2013-10-01

Publications (1)

Publication Number Publication Date
WO2015050379A1 true WO2015050379A1 (fr) 2015-04-09

Family

ID=52778922

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2014/009272 WO2015050379A1 (fr) 2013-10-01 2014-10-01 Nouveau dérivé de quinolinone et son utilisation

Country Status (2)

Country Link
KR (1) KR101731102B1 (fr)
WO (1) WO2015050379A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106146464A (zh) * 2015-04-10 2016-11-23 复旦大学 喹啉酮类化合物及其制备方法和用途
WO2018033455A1 (fr) 2016-08-15 2018-02-22 Bayer Cropscience Aktiengesellschaft Dérivés hétérocycliques bicycliques condensés utilisés comme pesticides
WO2018174288A1 (fr) 2017-03-24 2018-09-27 大正製薬株式会社 Dérivé de 2(1h)-quinolinone
CN109535305A (zh) * 2018-11-26 2019-03-29 贵州省化工研究院 一种大黄酸吸附材料的制备方法
CN111187169A (zh) * 2019-08-27 2020-05-22 福建永晶科技股份有限公司 氟苯衍生物和苯甲酸次氟盐衍生物的制备工艺
RU2732297C2 (ru) * 2018-11-14 2020-09-15 Общество с ограниченной ответственностью "Гурус БиоФарм" Производные нестероидных противовоспалительных средств
AU2016317968B2 (en) * 2015-09-04 2021-03-25 Shin Poong Pharmaceutical Co., Ltd. Compound having effect of inhibiting platelet aggregation and salt thereof, and composition for preventing or treating thrombotic diseases, containing same
US20230159493A1 (en) * 2021-09-13 2023-05-25 Eli Lilly And Company Ahr agonists

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991007401A1 (fr) * 1989-11-13 1991-05-30 Schering Corporation 1-(aryle ou arylalkyle)-2(1h)-quinolones 3-substituees
US20050222194A1 (en) * 2001-12-14 2005-10-06 Daniel Dube Quinolinones as prostaglandin receptor ligands
US20120184548A1 (en) * 2011-01-19 2012-07-19 Romyr Dominique Carboxylic acid aryl amides

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991007401A1 (fr) * 1989-11-13 1991-05-30 Schering Corporation 1-(aryle ou arylalkyle)-2(1h)-quinolones 3-substituees
US20050222194A1 (en) * 2001-12-14 2005-10-06 Daniel Dube Quinolinones as prostaglandin receptor ligands
US20120184548A1 (en) * 2011-01-19 2012-07-19 Romyr Dominique Carboxylic acid aryl amides

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
IWAMURA, H. ET AL.: "In Vitro and in Vivo Pharmacological Characterization of JTE-907, a Novel Selective Ligand for Cannabinoid CB2 Receptor", THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 296, no. 2, 2001, pages 420 - 425 *
MEHTA, M. ET AL.: "Influence of Novel KGFR Tyrosine Kinase Inhibitors on KGF-mediated Proliferation of Breast Cancer.", ANTICANCER RESEARCH., vol. 30, 2010, pages 4883 - 4890 *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106146464A (zh) * 2015-04-10 2016-11-23 复旦大学 喹啉酮类化合物及其制备方法和用途
AU2016317968B2 (en) * 2015-09-04 2021-03-25 Shin Poong Pharmaceutical Co., Ltd. Compound having effect of inhibiting platelet aggregation and salt thereof, and composition for preventing or treating thrombotic diseases, containing same
WO2018033455A1 (fr) 2016-08-15 2018-02-22 Bayer Cropscience Aktiengesellschaft Dérivés hétérocycliques bicycliques condensés utilisés comme pesticides
WO2018174288A1 (fr) 2017-03-24 2018-09-27 大正製薬株式会社 Dérivé de 2(1h)-quinolinone
KR20190133667A (ko) 2017-03-24 2019-12-03 다이쇼 세이야꾸 가부시끼가이샤 2(1h)-퀴놀리논 유도체
RU2732297C2 (ru) * 2018-11-14 2020-09-15 Общество с ограниченной ответственностью "Гурус БиоФарм" Производные нестероидных противовоспалительных средств
CN109535305A (zh) * 2018-11-26 2019-03-29 贵州省化工研究院 一种大黄酸吸附材料的制备方法
CN109535305B (zh) * 2018-11-26 2021-12-03 贵州省化工研究院 一种大黄酸吸附材料的制备方法
CN111187169A (zh) * 2019-08-27 2020-05-22 福建永晶科技股份有限公司 氟苯衍生物和苯甲酸次氟盐衍生物的制备工艺
CN111187169B (zh) * 2019-08-27 2023-05-09 福建永晶科技股份有限公司 氟苯衍生物和苯甲酸次氟盐衍生物的制备工艺
US20230159493A1 (en) * 2021-09-13 2023-05-25 Eli Lilly And Company Ahr agonists

Also Published As

Publication number Publication date
KR20160055181A (ko) 2016-05-17
KR101731102B1 (ko) 2017-04-27

Similar Documents

Publication Publication Date Title
WO2015050379A1 (fr) Nouveau dérivé de quinolinone et son utilisation
US20060247439A1 (en) Mchir antagonists
US9540360B2 (en) Sulfonamide compounds having TRPM8 antagonistic activity
KR20050065624A (ko) 염증성 및 알레르기 질환의 치료에 유용한 신규한트리사이클릭 화합물, 이의 제조 방법 및 이를 함유하는약제 조성물
CZ20033368A3 (en) Thiophene derivatives as antiviral agents for flavivirus infection
WO2011055270A1 (fr) Antagonistes des récepteurs crth2 à base d'indole
SK10102003A3 (sk) Acylované indanylamíny, farmaceutická kompozícia s ich obsahom, spôsob syntézy a ich použitie ako liečivá
JP2009529496A (ja) 誘導型一酸化窒素シンターゼ抑制剤として有用なキノロン類
KR20060121818A (ko) Ｎ-치환된 벤즈이미다졸릴 ｃ-ｋｉｔ 억제제
JPH0625134B2 (ja) 新規な複素環化合物
KR20070086865A (ko) Ｎ-치환된 벤즈이미다졸일 ｃ-ｋｉｔ 억제제 및 조합적인벤즈이미다졸 라이브러리
KR20000010905A (ko) 도파민 d3 수용체의 조절제로서의 테트라히드로이소퀴놀린유도체
JP2010507664A (ja) ベンズイミダゾール化合物
KR100745307B1 (ko) 아미노퀴놀린 유도체 및 아데노신 ａ３ 리간드로서의 이의 용도
EP0459561B1 (fr) Dérivés de dioxo-tétrahydroquinoline
AU2002304358A1 (en) Aminoquinoline and aminopyridine derivatives and their use as adenosine A3 ligands
JP2000026430A (ja) ２、５、６−置換ベンズイミダゾール化合物誘導体
AU2011295408B2 (en) Substituted 2-oxo- and 2-thioxo-dihydroquinoline-3-carboxamides as KCNQ2/3 modulators
WO2014042238A1 (fr) Composé de sulfonamide
US20090048295A1 (en) Substituted 5,6,7,8-tetrahydroquinoline derivatives, compositions, and methods of use thereof
KR20070034136A (ko) 이미다조퀴놀린 유도체
JP5323059B2 (ja) （（フェニル）イミダゾリル）メチルヘテロアリール化合物
JP2000226373A (ja) アミン誘導体、その製造法および剤
JP2001508402A (ja) 置換ベンズアミド誘導体およびそれらの抗痙攣薬としての使用
WO2011161615A1 (fr) Inhibiteurs de la 5-lipoxygénase

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: 14850339

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 20167008791

Country of ref document: KR

Kind code of ref document: A

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 1205N DATED 07.06.2016)

122 Ep: pct application non-entry in european phase

Ref document number: 14850339

Country of ref document: EP

Kind code of ref document: A1