WO2009035067A1 - Agonistes des récepteurs des glucocorticoïdes constitués de dérivés de la 1,3,3-triméthyle-7-phényle-3,4-dihydro-1h-quinoxaline-2-one - Google Patents

Agonistes des récepteurs des glucocorticoïdes constitués de dérivés de la 1,3,3-triméthyle-7-phényle-3,4-dihydro-1h-quinoxaline-2-one Download PDF

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Publication number
WO2009035067A1
WO2009035067A1 PCT/JP2008/066512 JP2008066512W WO2009035067A1 WO 2009035067 A1 WO2009035067 A1 WO 2009035067A1 JP 2008066512 W JP2008066512 W JP 2008066512W WO 2009035067 A1 WO2009035067 A1 WO 2009035067A1
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WIPO (PCT)
Prior art keywords
quinoxalin
dihydro
phenyl
glucocorticoid receptor
tri
Prior art date
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PCT/JP2008/066512
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English (en)
Japanese (ja)
Inventor
Masatomo Kato
Miwa Takai
Takahiro Matsuyama
Tatsuji Kurose
Yumi Hagiwara
Mamoru Matsuda
Toshiyuki Mori
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Santen Pharmaceutical Co., Ltd.
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Publication of WO2009035067A1 publication Critical patent/WO2009035067A1/fr

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    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/44—Benzopyrazines 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
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
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    • A61P17/00—Drugs for dermatological disorders
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A61P31/06—Antibacterial agents for tuberculosis
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/44—Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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    • 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
    • C07D401/12—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 chain containing hetero atoms as chain links
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    • 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
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    • 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
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    • 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
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Cardiology (AREA)
  • Pain & Pain Management (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Heart & Thoracic Surgery (AREA)
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  • Ophthalmology & Optometry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Transplantation (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La présente invention concerne un agoniste des récepteurs des glucocorticoïdes constitué d'un dérivé de la 1,3,3-triméthyle-7-phényle-3,4-dihydro-1H-quinoxaline-2-one représenté par la formule générale (1) ou l'un de ses sels et de nouveaux effets pharmacologiques de l'agoniste : [Formule chimique 1] (1) (2a) (4a) (3a) (5a) dans laquelle R1 est un groupe représenté par la formule générale (2a), (3a), (4a) ou (5a) ; R2 et R3 peuvent être identiques ou différents l'un de l'autre et ils représentent chacun un atome d'hydrogène, un groupe halogéno, alkyle inférieur, hydroxy, hydroxy estérifié, ou analogues ; R4 représente un groupe alkyle inférieur ; R5, R6, R7 et R8 représentent chacun un groupe halogéno, alkyle inférieur, hydroxy, alcoxy inférieur, ou analogues ; et m, n, p et q valent chacun 0, 1 ou 2.
PCT/JP2008/066512 2007-09-13 2008-09-12 Agonistes des récepteurs des glucocorticoïdes constitués de dérivés de la 1,3,3-triméthyle-7-phényle-3,4-dihydro-1h-quinoxaline-2-one WO2009035067A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2007-237877 2007-09-13
JP2007237877 2007-09-13

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WO2009035067A1 true WO2009035067A1 (fr) 2009-03-19

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WO (1) WO2009035067A1 (fr)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010029986A1 (fr) * 2008-09-12 2010-03-18 参天製薬株式会社 Agoniste de récepteur de glucocorticoïde comprenant un nouveau dérivé de 1,2,3,4-tétrahydroquinoxaline contenant un groupe phényle ayant une structure d’ester d’acide sulfonique introduite dans celui-ci en tant que substituant
US8193187B2 (en) 2007-05-29 2012-06-05 Santen Pharmaceutical Co., Ltd. 1,2,3,4-tetrahydroquinoxaline compound with a phenyl group substituent having a sulfonic acid ester structure or a sulfonic acid amide structure introduced therein and having glucocorticoid receptor-binding activity
US8551991B2 (en) 2006-03-14 2013-10-08 Santen Pharmaceutical Co., Ltd. 1,2,3,4-tetrahydroquinoxaline derivative having glucocorticoid receptor binding activity
CN107922356A (zh) * 2015-08-25 2018-04-17 参天制药株式会社 [4‑(1,3,3‑三甲基‑2‑氧代‑3,4‑二氢‑1h‑喹喔啉‑7‑基)苯氧基]乙基氧基化合物或其盐
WO2018230713A1 (fr) 2017-06-16 2018-12-20 学校法人同志社 Composés ayant une activité inhibitrice de caspase, agent pharmaceutique les contenant pour le traitement ou la prévention des symptômes, troubles ou maladies de l'endothélium cornéen, et application dudit agent pharmaceutique
WO2019121606A1 (fr) 2017-12-18 2019-06-27 Grünenthal GmbH Pyrrolidine amides i substitués
WO2019121611A1 (fr) 2017-12-18 2019-06-27 Grünenthal GmbH Pyrrolidine amides ii substitués
WO2020016452A1 (fr) 2018-07-20 2020-01-23 Grünenthal GmbH Nouveaux dérivés de triazolo quinoxaline substitués
WO2020016453A1 (fr) 2018-07-20 2020-01-23 Grünenthal GmbH Dérivés de triazolo-quinoxaline substitués
WO2020144375A1 (fr) 2019-01-11 2020-07-16 Grünenthal GmbH Amides de pyrrolidine iii substitués
WO2020254552A2 (fr) 2019-06-19 2020-12-24 Grünenthal GmbH Amides de pyrrolidine substitués v
WO2020254551A1 (fr) 2019-06-19 2020-12-24 Grünenthal GmbH Amides de pyrrolidine substitués iv
WO2021144440A1 (fr) 2020-01-17 2021-07-22 Grünenthal GmbH Dérivés de quinoxaline en tant que modulateurs du récepteur des glucocorticoïdes
WO2021144439A1 (fr) 2020-01-17 2021-07-22 Grünenthal GmbH Dérivés de quinoxaline
WO2022008705A1 (fr) 2020-07-09 2022-01-13 Grünenthal GmbH Pyrrolidine amines substituées et amides en tant que médiateur du récepteur de glucocortoïde
US11433090B2 (en) 2017-06-16 2022-09-06 The Doshisha mTOR-inhibitor-containing medicine for treating or preventing ophthalmic symptoms, disorders, or diseases, and application thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006015259A2 (fr) * 2004-07-28 2006-02-09 Irm Llc Composes et compositions comme modulateurs de recepteurs steroides
WO2007032556A1 (fr) * 2005-09-14 2007-03-22 Santen Pharmaceutical Co., Ltd. Nouveau dérivé de 1-2-dihydroquinoline présentant une activité de liaison aux récepteurs glucocorticoïdes
WO2007105766A1 (fr) * 2006-03-14 2007-09-20 Santen Pharmaceutical Co., Ltd. Nouveau derive 1,2,3,4-tetrahydroquinoxaline ayant une activite de liaison a un recepteur de glucocorticoide

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006015259A2 (fr) * 2004-07-28 2006-02-09 Irm Llc Composes et compositions comme modulateurs de recepteurs steroides
WO2007032556A1 (fr) * 2005-09-14 2007-03-22 Santen Pharmaceutical Co., Ltd. Nouveau dérivé de 1-2-dihydroquinoline présentant une activité de liaison aux récepteurs glucocorticoïdes
WO2007105766A1 (fr) * 2006-03-14 2007-09-20 Santen Pharmaceutical Co., Ltd. Nouveau derive 1,2,3,4-tetrahydroquinoxaline ayant une activite de liaison a un recepteur de glucocorticoide

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8975256B2 (en) 2006-03-14 2015-03-10 Santen Pharmaceutical Co., Ltd. 1,2,3,4-tetrahydroquinoxaline compounds having glucocorticoid receptor binding activity
US8551991B2 (en) 2006-03-14 2013-10-08 Santen Pharmaceutical Co., Ltd. 1,2,3,4-tetrahydroquinoxaline derivative having glucocorticoid receptor binding activity
US8193187B2 (en) 2007-05-29 2012-06-05 Santen Pharmaceutical Co., Ltd. 1,2,3,4-tetrahydroquinoxaline compound with a phenyl group substituent having a sulfonic acid ester structure or a sulfonic acid amide structure introduced therein and having glucocorticoid receptor-binding activity
US8569493B2 (en) 2007-05-29 2013-10-29 Santen Pharmaceutical Co., Ltd. Method for treating a homeostasis-related disease or glaucoma by administering a 1,2,3,4-tetrahyroquinoxaline compound
EA018420B1 (ru) * 2008-09-12 2013-07-30 Сантен Фармасьютикал Ко., Лтд. Агонист глюкокортикоидного рецептора, содержащий новые производные 1,2,3,4-тетрагидрохиноксалина с фенильной группой, имеющей структуру эфира сульфоновой кислоты, введенной в нее в качестве заместителя
US8664221B2 (en) 2008-09-12 2014-03-04 Santen Pharmaceutical Co., Ltd. Method for treating an inflammatory disease by administering a 1,2,3,4- tetrahydroquinoxaline compound containing a phenyl group having a sulfonic acid ester structure introduced therein as a substituent
WO2010029986A1 (fr) * 2008-09-12 2010-03-18 参天製薬株式会社 Agoniste de récepteur de glucocorticoïde comprenant un nouveau dérivé de 1,2,3,4-tétrahydroquinoxaline contenant un groupe phényle ayant une structure d’ester d’acide sulfonique introduite dans celui-ci en tant que substituant
CN107922356A (zh) * 2015-08-25 2018-04-17 参天制药株式会社 [4‑(1,3,3‑三甲基‑2‑氧代‑3,4‑二氢‑1h‑喹喔啉‑7‑基)苯氧基]乙基氧基化合物或其盐
WO2018230713A1 (fr) 2017-06-16 2018-12-20 学校法人同志社 Composés ayant une activité inhibitrice de caspase, agent pharmaceutique les contenant pour le traitement ou la prévention des symptômes, troubles ou maladies de l'endothélium cornéen, et application dudit agent pharmaceutique
US11433090B2 (en) 2017-06-16 2022-09-06 The Doshisha mTOR-inhibitor-containing medicine for treating or preventing ophthalmic symptoms, disorders, or diseases, and application thereof
US10626106B2 (en) 2017-12-18 2020-04-21 Gruenenthal Gmbh Substituted pyrrolidine amides I
WO2019121606A1 (fr) 2017-12-18 2019-06-27 Grünenthal GmbH Pyrrolidine amides i substitués
WO2019121611A1 (fr) 2017-12-18 2019-06-27 Grünenthal GmbH Pyrrolidine amides ii substitués
WO2020016453A1 (fr) 2018-07-20 2020-01-23 Grünenthal GmbH Dérivés de triazolo-quinoxaline substitués
CN112673009A (zh) * 2018-07-20 2021-04-16 格吕伦塔尔有限公司 被取代的三唑并喹喔啉衍生物
US10981918B2 (en) 2018-07-20 2021-04-20 Grünenthal GmbH Further substituted triazolo quinoxaline derivatives
WO2020016452A1 (fr) 2018-07-20 2020-01-23 Grünenthal GmbH Nouveaux dérivés de triazolo quinoxaline substitués
CN112673009B (zh) * 2018-07-20 2023-09-19 格吕伦塔尔有限公司 被取代的三唑并喹喔啉衍生物
US11981677B2 (en) 2018-07-20 2024-05-14 Grünenthal GmbH Further substituted triazolo quinoxaline derivatives
WO2020144375A1 (fr) 2019-01-11 2020-07-16 Grünenthal GmbH Amides de pyrrolidine iii substitués
WO2020254552A2 (fr) 2019-06-19 2020-12-24 Grünenthal GmbH Amides de pyrrolidine substitués v
WO2020254551A1 (fr) 2019-06-19 2020-12-24 Grünenthal GmbH Amides de pyrrolidine substitués iv
WO2021144440A1 (fr) 2020-01-17 2021-07-22 Grünenthal GmbH Dérivés de quinoxaline en tant que modulateurs du récepteur des glucocorticoïdes
WO2021144439A1 (fr) 2020-01-17 2021-07-22 Grünenthal GmbH Dérivés de quinoxaline
WO2022008705A1 (fr) 2020-07-09 2022-01-13 Grünenthal GmbH Pyrrolidine amines substituées et amides en tant que médiateur du récepteur de glucocortoïde

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