JP2016503797A - ペリ−カルビノール - Google Patents
ペリ−カルビノール Download PDFInfo
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- JP2016503797A JP2016503797A JP2015549717A JP2015549717A JP2016503797A JP 2016503797 A JP2016503797 A JP 2016503797A JP 2015549717 A JP2015549717 A JP 2015549717A JP 2015549717 A JP2015549717 A JP 2015549717A JP 2016503797 A JP2016503797 A JP 2016503797A
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- Prior art keywords
- compound
- alkyl
- independently
- compound according
- pharmaceutically acceptable
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- 150000001875 compounds Chemical class 0.000 claims abstract description 168
- 238000000034 method Methods 0.000 claims abstract description 39
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- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract description 17
- 230000002207 retinal effect Effects 0.000 claims abstract description 17
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- 230000011506 response to oxidative stress Effects 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims description 80
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- 125000001424 substituent group Chemical group 0.000 claims description 22
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
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- 229910052794 bromium Inorganic materials 0.000 claims description 16
- 125000004429 atom Chemical group 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
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- 125000005270 trialkylamine group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
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- 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
-
- 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
-
- 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
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 nitrogen-containing ring
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (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)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Epidemiology (AREA)
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| BRPI0610308A8 (pt) | 2005-05-26 | 2017-04-25 | Neuron Systems Inc | Composições e métodos para o tratamento de doença retinal |
| WO2011072141A1 (en) | 2009-12-11 | 2011-06-16 | Neuron Systems, Inc. | Compositions and methods for the treatment of macular degeneration |
| GEP201706757B (en) | 2012-12-21 | 2017-10-25 | Alios Biopharma Inc | Substituted nucleosides, nucleotides and analogs thereof |
| EP2948149A4 (en) | 2013-01-23 | 2016-12-14 | Aldeyra Therapeutics Inc | BY TOXIC ALDEHYDIC DISEASES AND TREATMENT |
| SG11201505599YA (en) | 2013-01-25 | 2015-08-28 | Aldeyra Therapeutics Inc | Novel traps in the treatment of macular degeneration |
| KR20180073553A (ko) * | 2015-08-21 | 2018-07-02 | 알데이라 테라퓨틱스, 아이엔씨. | 알데히드 접합체 및 이의 용도 |
| MX2018002155A (es) | 2015-08-21 | 2018-06-08 | Aldeyra Therapeutics Inc | Compuestos deuterados y usos de los mismos. |
| WO2017147617A1 (en) | 2016-02-28 | 2017-08-31 | Aldeyra Therapeutics, Inc. | Treatment of allergic eye conditions with cyclodextrins |
| MX2018013472A (es) | 2016-05-09 | 2019-02-28 | Aldeyra Therapeutics Inc | Tratamiento de combinacion de trastornos y enfermedades inflamatorios oculares. |
| CN109640983A (zh) * | 2016-08-22 | 2019-04-16 | 奥尔德拉医疗公司 | 醛捕获化合物和其用途 |
| CN110431130A (zh) | 2017-03-16 | 2019-11-08 | 奥尔德拉医疗公司 | 多晶型化合物和其用途 |
| AU2018348174A1 (en) | 2017-10-10 | 2020-04-23 | Aldeyra Therapeutics, Inc. | Treatment of inflammatory disorders |
| EP3833660A4 (en) | 2018-08-06 | 2022-05-11 | Aldeyra Therapeutics, Inc. | POLYMORPHIC COMPOUNDS AND THEIR USES |
| CN113056353B (zh) | 2018-09-25 | 2022-11-01 | 奥尔德拉医疗公司 | 用于治疗干眼病的调配物 |
| WO2020198064A1 (en) | 2019-03-26 | 2020-10-01 | Aldeyra Therapeutics, Inc. | Ophthalmic formulations and uses thereof |
| WO2020223717A1 (en) | 2019-05-02 | 2020-11-05 | Aldeyra Therapeutics, Inc. | Process for preparation of aldehyde scavenger and intermediates |
| JP2022530967A (ja) | 2019-05-02 | 2022-07-05 | アルデイラ セラピューティクス， インコーポレイテッド | 多形化合物およびその使用 |
| WO2021231792A1 (en) | 2020-05-13 | 2021-11-18 | Aldeyra Therapeutics, Inc. | Pharmaceutical formulations and uses thereof |
| JP2023533855A (ja) | 2020-07-16 | 2023-08-04 | ダーマヴァント サイエンシーズ ゲーエムベーハー | イソキノリン化合物およびそのＡｈＲ不均衡の治療への使用 |
Family Cites Families (46)
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| US2086186A (en) | 1933-10-10 | 1937-07-06 | Us Rubber Co | Treatment of rubber |
| SU509046A1 (ru) | 1975-02-21 | 1984-06-23 | Всесоюзный научно-исследовательский химико-фармацевтический институт им.Серго Орджоникидзе | Производные 2-карбэтокси-3-аминоиндола,про вл ющие противовоспалительную активность, и способ их получени |
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| GB8610981D0 (en) | 1986-05-06 | 1986-06-11 | Ici America Inc | Quinoline amides |
| CA2054339C (en) | 1990-11-02 | 2002-12-24 | Francesco G. Salituro | 3-amidoindolyl derivatives |
| US5668117A (en) | 1991-02-22 | 1997-09-16 | Shapiro; Howard K. | Methods of treating neurological diseases and etiologically related symptomology using carbonyl trapping agents in combination with previously known medicaments |
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| US20050090553A1 (en) | 1992-06-30 | 2005-04-28 | Shapiro Howard K. | Compositions and method for treatment of chronic inflammatory diseases |
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| JP2001508029A (ja) | 1996-08-01 | 2001-06-19 | ダウ・アグロサイエンス・エル・エル・シー | 殺菌・殺カビ活性を有する４―置換キノリン誘導体 |
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| HUP0102612A2 (hu) | 1998-03-12 | 2001-11-28 | Novo Nordisk A/S | Fehérje-tirozinfoszfatázokat moduláló vegyületek és ezeket tartalmazó gyógyászati készítmények |
| US6498154B1 (en) | 1999-05-04 | 2002-12-24 | Wyeth | Cyclic regimens using quinazolinone and benzoxazine derivatives |
| WO2001041757A1 (en) | 1999-12-10 | 2001-06-14 | Senju Pharmaceutical Co., Ltd. | Cyclodextrin-containing pharmaceutical composition |
| FR2827599A1 (fr) | 2001-07-20 | 2003-01-24 | Neuro3D | Composes derives de quinoleine et quinoxaline,preparation et utilisations |
| US20060014786A1 (en) | 2002-05-17 | 2006-01-19 | Rajeev Raut | Opthalmic pharmaceutical compositions and methods for treating ocular inflammation |
| CA2451267A1 (en) | 2002-12-13 | 2004-06-13 | Warner-Lambert Company Llc | Pharmaceutical uses for alpha2delta ligands |
| EP3326623A1 (en) | 2003-03-14 | 2018-05-30 | University of Washington | Retinoid replacements and opsin agonists and methods for the use thereof |
| US20060111318A1 (en) | 2003-04-18 | 2006-05-25 | Advanced Medicine Research Institute | Agent for treating eye diseases |
| EP1621199B8 (en) | 2003-04-18 | 2011-01-19 | Advanced Medicine Research Institute | Remedies for diseases to be applied to eye |
| US7297709B2 (en) | 2003-05-22 | 2007-11-20 | Abbott Laboratories | Indazole, benzisoxazole, and benzisothiazole kinase inhibitors |
| ES2426288T3 (es) | 2003-10-15 | 2013-10-22 | Ube Industries, Ltd. | Novedoso derivado de imidazol |
| CA2546042A1 (en) | 2003-11-20 | 2005-06-09 | Othera Pharmaceuticals, Inc. | Amelioration of macular degeneration and other ophthalmic diseases |
| US20050197292A1 (en) | 2004-01-30 | 2005-09-08 | Glennda Smithson | Compositions and methods for treating T-cell mediated pathological conditions |
| AU2005215778B2 (en) | 2004-02-17 | 2009-03-12 | President And Fellows Of Harvard College | Management of ophthalmologic disorders, including macular degeneration |
| US20050234018A1 (en) | 2004-04-15 | 2005-10-20 | Allergan, Inc. | Drug delivery to the back of the eye |
| WO2006002473A1 (en) | 2004-07-02 | 2006-01-12 | Adelaide Research & Innovation Pty Ltd | Method of controlling damage mediated by alpha, beta-unsaturated aldehydes |
| AU2005302608A1 (en) * | 2004-10-28 | 2006-05-11 | Merck & Co., Inc. | Pyrimidine and quinoline potentiators of metabotropic glutamate receptors |
| TW200640443A (en) | 2005-02-23 | 2006-12-01 | Alcon Inc | Methods for treating ocular angiogenesis, retinal edema, retinal ischemia, and diabetic retinopathy using selective RTK inhibitors |
| BRPI0610308A8 (pt) | 2005-05-26 | 2017-04-25 | Neuron Systems Inc | Composições e métodos para o tratamento de doença retinal |
| WO2007118276A1 (en) * | 2006-04-14 | 2007-10-25 | Prana Biotechnology Ltd | Method of treatment of age-related macular degeneration(amd) |
| RU2009106461A (ru) * | 2006-07-25 | 2010-08-27 | Энвиво Фармасьютикалз, Инк. (Us) | Хинолиновые производные |
| SG185276A1 (en) | 2007-10-05 | 2012-11-29 | Acucela Inc | Alkoxy compounds for disease treatment |
| AU2009282076A1 (en) | 2008-08-12 | 2010-02-18 | Sirtris Pharmaceuticals, Inc. | Benzoxazoles, benzthiazoles and related analogs as sirtuin modulators |
| WO2010133672A1 (en) | 2009-05-20 | 2010-11-25 | Clanotech Ab | Derivatives of quinoline-3-carboxylic acid and their medical use |
| WO2011008202A1 (en) | 2009-07-15 | 2011-01-20 | Vanderbilt University | Isoketal scavengers and mitigation of disorders involving oxidative injury |
| WO2011071995A2 (en) | 2009-12-08 | 2011-06-16 | Case Western Reserve University | Compounds and methods of treating ocular disorders |
| WO2011072141A1 (en) | 2009-12-11 | 2011-06-16 | Neuron Systems, Inc. | Compositions and methods for the treatment of macular degeneration |
| WO2012097173A2 (en) | 2011-01-12 | 2012-07-19 | Ventirx Pharmaceuticals, Inc. | Substituted benzoazepines as toll-like receptor modulators |
| WO2012105887A1 (en) | 2011-01-31 | 2012-08-09 | Tim Bowden | Active principle for mitigating undesired medical conditions |
| WO2015187942A1 (en) | 2014-06-04 | 2015-12-10 | Case Western Reserve University | Compositions and methods of treating diabetic retinopathy |
| EP2948149A4 (en) | 2013-01-23 | 2016-12-14 | Aldeyra Therapeutics Inc | BY TOXIC ALDEHYDIC DISEASES AND TREATMENT |
| SG11201505599YA (en) | 2013-01-25 | 2015-08-28 | Aldeyra Therapeutics Inc | Novel traps in the treatment of macular degeneration |
| US10363231B2 (en) | 2014-11-24 | 2019-07-30 | Case Western Reserve University | Compounds and methods of treating ocular disorders |
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- 2013-12-19 WO PCT/US2013/076592 patent/WO2014100425A1/en not_active Ceased
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| MX2015007916A (es) | 2016-04-07 |
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| EP2935220A4 (en) | 2016-04-27 |
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| SG11201504859YA (en) | 2015-07-30 |
| AU2013361314A1 (en) | 2015-07-02 |
| US9604997B2 (en) | 2017-03-28 |
| IL239178A0 (en) | 2015-07-30 |
| RU2015120478A (ru) | 2017-01-25 |
| EP2935220A1 (en) | 2015-10-28 |
| WO2014100425A1 (en) | 2014-06-26 |
| HK1217325A1 (zh) | 2017-01-06 |
| CL2015001754A1 (es) | 2015-11-06 |
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