CA2903103C - Coumarin derivatives and methods of use in treating cystic fibrosis, chronic obstructive pulmonary disease, and misfolded protein disorders - Google Patents
Coumarin derivatives and methods of use in treating cystic fibrosis, chronic obstructive pulmonary disease, and misfolded protein disorders Download PDFInfo
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- CA2903103C CA2903103C CA2903103A CA2903103A CA2903103C CA 2903103 C CA2903103 C CA 2903103C CA 2903103 A CA2903103 A CA 2903103A CA 2903103 A CA2903103 A CA 2903103A CA 2903103 C CA2903103 C CA 2903103C
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- 201000003883 Cystic fibrosis Diseases 0.000 title claims abstract description 43
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 17
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 16
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title abstract description 83
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 18
- 208000035475 disorder Diseases 0.000 title description 7
- 150000001893 coumarin derivatives Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 291
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 208000007153 proteostasis deficiencies Diseases 0.000 claims abstract description 24
- 150000004820 halides Chemical class 0.000 claims abstract description 21
- 102000011045 Chloride Channels Human genes 0.000 claims abstract description 13
- 108010062745 Chloride Channels Proteins 0.000 claims abstract description 13
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- 238000012545 processing Methods 0.000 claims abstract description 6
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 47
- 102000012605 Cystic Fibrosis Transmembrane Conductance Regulator Human genes 0.000 claims description 43
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 29
- -1 nitro, cyano, azido, thiocyanato Chemical group 0.000 claims description 27
- 230000035772 mutation Effects 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
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- 125000003118 aryl group Chemical group 0.000 claims description 13
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- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- 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
- C07D417/02—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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/12—Mucolytics
-
- 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
- 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
- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- 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)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epidemiology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
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| US201361788353P | 2013-03-15 | 2013-03-15 | |
| US61/788,353 | 2013-03-15 | ||
| PCT/US2014/027079 WO2014152213A2 (en) | 2013-03-15 | 2014-03-14 | Coumarin derivatives and methods of use in treating cystic fibrosis, chronic obstructive pulmonary disease, and misfolded protein disorders |
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| US (1) | US9815825B2 (OSRAM) |
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| CN (1) | CN105121437B (OSRAM) |
| AU (1) | AU2014240026B2 (OSRAM) |
| CA (1) | CA2903103C (OSRAM) |
| MX (1) | MX372775B (OSRAM) |
| WO (1) | WO2014152213A2 (OSRAM) |
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| CA2836463A1 (en) | 2011-05-17 | 2012-11-22 | Discoverybiomed Inc. | Treating protein folding disorders with small molecule cftr correctors |
| AU2013348019A1 (en) | 2012-11-20 | 2015-06-04 | Discoverybiomed, Inc. | Small molecule bicyclic and tricyclic CFTR correctors |
| CA2891962A1 (en) | 2012-11-20 | 2014-05-03 | Discoverybiomed, Inc. | Small molecule cftr correctors |
| AU2014240026B2 (en) | 2013-03-15 | 2018-06-14 | Discoverybiomed, Inc. | Coumarin derivatives and methods of use in treating cystic fibrosis, chronic obstructive pulmonary disease, and misfolded protein disorders |
| MX379292B (es) | 2013-03-15 | 2025-03-11 | Discoverybiomed Inc | Derivados de cumarina y metodos de uso en el tratamiento de enfermedades hiperproliferativas. |
| WO2015196071A1 (en) | 2014-06-19 | 2015-12-23 | Proteostasis Therapeutics, Inc. | Compounds, compositions and methods of increasing cftr activity |
| WO2016057572A1 (en) | 2014-10-06 | 2016-04-14 | Mark Thomas Miller | Modulators of cystic fibrosis transmembrane conductance regulator |
| WO2016105477A1 (en) | 2014-12-23 | 2016-06-30 | Proteostasis Therapeutics, Inc | Derivatives of 5-phenyl- or 5-heteroarylthiazol-2-carboxylic amide useful for the treatment of inter alia cystic fibrosis |
| US10344023B2 (en) | 2014-12-23 | 2019-07-09 | Proteostasis Therapeutics, Inc. | Derivatives of 3-heteroarylisoxazol-5-carboxylic amide useful for the treatment of inter alia cystic fibrosis |
| MA41253A (fr) | 2014-12-23 | 2017-10-31 | Proteostasis Therapeutics Inc | Composés, compositions et procédés pour augmenter l'activité du cftr |
| MA42488A (fr) | 2015-07-24 | 2018-05-30 | Proteostasis Therapeutics Inc | Composés, compositions et procédés pour augmenter l'activité du cftr |
| AR108203A1 (es) | 2016-04-07 | 2018-07-25 | Proteostasis Therapeutics Inc | Compuestos, composiciones y métodos para modular cftr (regulador de la conductancia transmembrana de la fibrosis quística) |
| WO2017223188A1 (en) | 2016-06-21 | 2017-12-28 | Proteostasis Therapeutics, Inc. | Compounds, compositions, and methods for increasing cftr activity |
| WO2018081381A1 (en) | 2016-10-26 | 2018-05-03 | Proteostasis Therapeutics, Inc | Pyridazine derivatives, compositions and methods for modulating cftr |
| CA3041675A1 (en) | 2016-10-26 | 2018-05-03 | Proteostasis Therapeutics, Inc. | N-phenyl-2-(3-phenyl-6-oxo-1,6-dihydropyridazin-1-yl)acetamide derivatives for treating cystic fibrosis |
| US20190248779A1 (en) | 2016-10-26 | 2019-08-15 | Proteostasis Therapeutics, Inc. | Compounds, compositions, and methods for increasing cftr activity |
| MA49061A (fr) | 2017-04-28 | 2021-04-21 | Proteostasis Therapeutics Inc | Dérivés 4-sulfonylaminocarbonylquinoline pour augmenter l'activité cftr |
| IL273752B2 (en) | 2017-10-06 | 2023-12-01 | Proteostasis Therapeutics Inc | Ingredients, compounds and methods for increasing CFTR activity |
| WO2019136314A1 (en) | 2018-01-05 | 2019-07-11 | The Curators Of The University Of Missouri | Compounds and methods for treatment of cystic fibrosis |
| EP3846801B1 (en) | 2018-09-09 | 2025-03-12 | Qanatpharma AG | Use of cftr modulators for treating cerebrovascular conditions |
| CN110156761B (zh) * | 2019-06-18 | 2022-08-09 | 郑州大学 | 含香豆素-联苯骨架化合物、制备方法及其应用 |
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| JPS5566580A (en) | 1978-11-11 | 1980-05-20 | Kaken Pharmaceut Co Ltd | Coumarin derivative, its preparation and antiallergic agent containing the same as effective component |
| DE10133665A1 (de) * | 2001-07-11 | 2003-01-30 | Boehringer Ingelheim Pharma | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Herstellung |
| US20030055263A1 (en) | 2001-07-11 | 2003-03-20 | Boehringer Ingelheim Pharma Kg | Carboxylic acid derivatives, medicaments comprising these compounds, their use and processes for their production |
| US6822097B1 (en) * | 2002-02-07 | 2004-11-23 | Amgen, Inc. | Compounds and methods of uses |
| WO2003105842A1 (en) | 2002-06-13 | 2003-12-24 | Novuspharma S.P.A. | Derivatives of chromen-2-one as inhibitors of vegf production in mammalian cells |
| CN101076703A (zh) | 2004-10-13 | 2007-11-21 | Ptc医疗公司 | 用于无义抑制的化合物及其使用方法 |
| KR20070067165A (ko) | 2004-10-13 | 2007-06-27 | 피티씨 테라퓨틱스, 인크. | 넌센스 변이 억제용 화합물, 및 이의 사용 방법 |
| MX2007004488A (es) * | 2004-10-13 | 2007-09-11 | Wyeth Corp | Analogos de anilino-pirimidina n-bencenosulfonilo sustituidos. |
| CN101351208A (zh) | 2005-11-01 | 2009-01-21 | 康乃尔研究基金会有限公司 | 减少细胞胆固醇水平和/或治疗或预防磷脂质病 |
| US20090012148A1 (en) | 2005-11-01 | 2009-01-08 | Maxfield Frederick R | Reducing cellular cholesterol levels and/or treating or preventing phospholipidosis |
| JP2011507811A (ja) | 2007-12-13 | 2011-03-10 | インディアナ・ユニバーシティ・リサーチ・アンド・テクノロジー・コーポレーション | 哺乳動物のｓ−ニトロソグルタチオンレダクターゼを阻害するための材料および方法 |
| WO2010111713A2 (en) * | 2009-03-27 | 2010-09-30 | Zacharon Pharmaceuticals, Inc. | N-linked glycan biosynthesis modulators |
| ITMI20111068A1 (it) * | 2011-06-14 | 2012-12-15 | Azienda Ospedaliera Universitaria I Ntegrata Di Ve | Trimetilangelicina come correttore di cftr in cellule dell'epitelio bronchiale |
| MX379292B (es) * | 2013-03-15 | 2025-03-11 | Discoverybiomed Inc | Derivados de cumarina y metodos de uso en el tratamiento de enfermedades hiperproliferativas. |
| AU2014240026B2 (en) | 2013-03-15 | 2018-06-14 | Discoverybiomed, Inc. | Coumarin derivatives and methods of use in treating cystic fibrosis, chronic obstructive pulmonary disease, and misfolded protein disorders |
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| US9815825B2 (en) | 2017-11-14 |
| EP2970248B1 (en) | 2020-04-22 |
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| AU2014240026A1 (en) | 2015-08-20 |
| MX2015013173A (es) | 2016-04-04 |
| WO2014152213A3 (en) | 2014-11-13 |
| EP2970248A2 (en) | 2016-01-20 |
| CN105121437B (zh) | 2018-12-04 |
| AU2014240026B2 (en) | 2018-06-14 |
| US20160024065A1 (en) | 2016-01-28 |
| HK1218420A1 (en) | 2017-02-17 |
| KR20150131309A (ko) | 2015-11-24 |
| CN105121437A (zh) | 2015-12-02 |
| WO2014152213A2 (en) | 2014-09-25 |
| EP2970248A4 (en) | 2017-01-11 |
| MX372775B (es) | 2020-06-29 |
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