RU2692775C2 - Производные нафтиридина в качестве антагонистов альфа v бета 6 интегрина для лечения, в частности, фиброзных заболеваний - Google Patents
Производные нафтиридина в качестве антагонистов альфа v бета 6 интегрина для лечения, в частности, фиброзных заболеваний Download PDFInfo
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- RU2692775C2 RU2692775C2 RU2017114355A RU2017114355A RU2692775C2 RU 2692775 C2 RU2692775 C2 RU 2692775C2 RU 2017114355 A RU2017114355 A RU 2017114355A RU 2017114355 A RU2017114355 A RU 2017114355A RU 2692775 C2 RU2692775 C2 RU 2692775C2
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- Prior art keywords
- methyl
- pyrazol
- pharmaceutically acceptable
- acceptable salt
- mmol
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- 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
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- 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
-
- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1417094.8A GB201417094D0 (en) | 2014-09-26 | 2014-09-26 | Novel compounds |
| GB1417094.8 | 2014-09-26 | ||
| PCT/EP2015/071782 WO2016046230A1 (en) | 2014-09-26 | 2015-09-22 | Naphthyridine derivatives as alpha v beta 6 integrin antagonists for the treatment of e.g. fibrotic diseases |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2017114355A RU2017114355A (ru) | 2018-10-29 |
| RU2017114355A3 RU2017114355A3 (enExample) | 2019-01-14 |
| RU2692775C2 true RU2692775C2 (ru) | 2019-06-27 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2017114355A RU2692775C2 (ru) | 2014-09-26 | 2015-09-22 | Производные нафтиридина в качестве антагонистов альфа v бета 6 интегрина для лечения, в частности, фиброзных заболеваний |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US10144733B2 (enExample) |
| EP (1) | EP3197894B1 (enExample) |
| JP (1) | JP6657196B2 (enExample) |
| KR (1) | KR20170053638A (enExample) |
| CN (1) | CN107074851B (enExample) |
| AU (1) | AU2015320863B2 (enExample) |
| BR (1) | BR112017006242A2 (enExample) |
| CA (1) | CA2962321A1 (enExample) |
| ES (1) | ES2811119T3 (enExample) |
| GB (1) | GB201417094D0 (enExample) |
| RU (1) | RU2692775C2 (enExample) |
| WO (1) | WO2016046230A1 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201305668D0 (en) | 2013-03-28 | 2013-05-15 | Glaxosmithkline Ip Dev Ltd | Avs6 Integrin Antagonists |
| GB201417011D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417018D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417002D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| GB201417094D0 (en) * | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| US20190144547A1 (en) * | 2015-11-23 | 2019-05-16 | Merck Patent Gmbh | Anti-alpha-v integrin antibody for the treatment of fibrosis and/or fibrotic disorders |
| WO2017157735A1 (de) | 2016-03-15 | 2017-09-21 | Bayer Cropscience Aktiengesellschaft | Substituierte sulfonylamide zur bekämpfung tierischer schädlinge |
| GB201604680D0 (en) | 2016-03-21 | 2016-05-04 | Glaxosmithkline Ip Dev Ltd | Chemical Compounds |
| CA3042710A1 (en) * | 2016-11-08 | 2018-05-17 | Bristol-Myers Squibb Company | Cyclobutane- and azetidine-containing mono and spirocyclic compounds as .alpha.v integrin inhibitors |
| BR112019009245A2 (pt) | 2016-11-08 | 2019-07-16 | Bristol-Myers Squibb Company | azol amidas e aminas como inibidores de alfav integrina |
| WO2018089353A1 (en) | 2016-11-08 | 2018-05-17 | Bristol-Myers Squibb Company | 3-substituted propionic acids as alpha v integrin inhibitors |
| EA201991123A1 (ru) | 2016-11-08 | 2019-11-29 | ИНДАЗОЛОВЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ АНТАГОНИСТОВ ИНТЕГРИНА αV | |
| PL3538528T3 (pl) * | 2016-11-08 | 2021-05-31 | Bristol-Myers Squibb Company | Amidy pirolu jako inhibitory integryny alfa v |
| EP3558303A4 (en) | 2016-12-23 | 2020-07-29 | Pliant Therapeutics, Inc. | AMINO ACID COMPOUNDS AND PROCESSES FOR USE |
| IL316954A (en) | 2017-02-28 | 2025-01-01 | Morphic Therapeutic Inc | (Alpha-V)(beta-6)integrin inhibitors |
| EP3760202A1 (en) | 2017-02-28 | 2021-01-06 | Morphic Therapeutic, Inc. | Inhibitors of (alpha-v)(beta-6) integrin |
| BR112020008893A2 (pt) | 2017-11-07 | 2020-10-13 | Bristol-Myers Squibb Company | derivados de pirrolopirazina como inibidores de alfa v integrina |
| UY38352A (es) | 2018-08-29 | 2020-03-31 | Morphic Therapeutic Inc | Inhibidores de integrina alfavbeta6 |
| UY38353A (es) | 2018-08-29 | 2020-03-31 | Morphic Therapeutic Inc | Inhibición de integrina alfavbeta6 |
| WO2020047208A1 (en) | 2018-08-29 | 2020-03-05 | Morphic Therapeutic, Inc. | Inhibitors of (alpha-v)(beta-6) integrin |
| GB202010626D0 (en) | 2020-07-10 | 2020-08-26 | Univ Nottingham | Compound |
| AU2023232562A1 (en) | 2022-03-08 | 2024-09-05 | Equashield Medical Ltd | Fluid transfer station in a robotic pharmaceutical preparation system |
| WO2024129931A1 (en) | 2022-12-14 | 2024-06-20 | Alnylam Pharmaceuticals, Inc. | ALPHA-V BETA-6(ανβ6) INTEGRIN LIGANDS FOR EXTRAHEPATIC DELIVERY |
| WO2025259747A2 (en) | 2024-06-12 | 2025-12-18 | Alnylam Pharmaceuticals, Inc. | Dystrophy myotonic protein kinase (dmpk) irna compositions and methods of use thereof |
| WO2025259743A1 (en) | 2024-06-12 | 2025-12-18 | Alnylam Pharmaceuticals, Inc. | Dual conjugate compounds for extrahepatic delivery |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001024797A1 (en) * | 1999-10-04 | 2001-04-12 | Merck & Co., Inc. | Integrin receptor antagonists |
| WO2005082889A1 (en) * | 2004-02-18 | 2005-09-09 | Janssen Pharmaceutica N.V. | Piperidinyl targeting compounds that selectively bind integrins |
| RU2296764C2 (ru) * | 2001-11-05 | 2007-04-10 | Новартис Аг | Производные нафтиридина, способ их получения и применение |
| RU2481347C2 (ru) * | 2007-08-01 | 2013-05-10 | Валеант Фармасьютикалс Интернэшнл | Производные нафтиридина в качестве модуляторов калиевых каналов |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1047425A4 (en) | 1997-12-17 | 2009-04-22 | Merck & Co Inc | INTEGRIN RECEPTOR ANTAGONISTS |
| BR9813769A (pt) | 1997-12-17 | 2000-10-10 | Merck & Co Inc | Composto, composição farmacêutica, e, processos para fabricar a mesma, para evocar um efeito antagonizante do receptor da integrina em um mamìfero em necessidade deste, para tratar ou prevenir uma condição mediada pelo antagonismo de um receptor da integrina em um mamìfero em necessidade deste, para inibir a reabsorção óssea em um mamìfero em necessidade deste, e para tratar o desenvolvimento tumoral em um mamìfero em necessidade deste. |
| DZ3263A1 (fr) | 1999-06-02 | 2000-12-07 | Merck & Co Inc | Antagonistes du recepteur de l'alpha v integrine |
| AU748949B2 (en) | 1999-06-23 | 2002-06-13 | Merck & Co., Inc. | Integrin receptor antagonists |
| CN1414966A (zh) | 1999-11-08 | 2003-04-30 | 麦克公司 | 用于制备咪唑烷酮αu蛋白拮抗剂的方法和中间体 |
| US7119098B2 (en) | 2000-06-15 | 2006-10-10 | Pharmacia Corporation | Heteroarylakanoic acids as intergrin receptor antagonists |
| US7056909B2 (en) | 2000-07-26 | 2006-06-06 | Merck & Co., Inc. | Alpha v integrin receptor antagonists |
| WO2002022616A2 (en) | 2000-09-14 | 2002-03-21 | Merck & Co., Inc. | Alpha v integrin receptor antagonists |
| EP1349548A4 (en) | 2001-01-03 | 2004-06-02 | Merck & Co Inc | METHOD AND COMPOSITIONS FOR TREATING PERIODONTOSIS |
| DE10112771A1 (de) | 2001-03-16 | 2002-09-26 | Merck Patent Gmbh | Inhibitoren des Integrins alpha¶v¶beta¶6¶ |
| BR0317600A (pt) | 2002-12-20 | 2005-11-29 | Pharmacia Corp | ácidos heteroarilalcanóicos como derivados de antagonistas de receptor de integrina |
| US6932865B2 (en) | 2003-04-11 | 2005-08-23 | Lockheed Martin Corporation | System and method of making single-crystal structures through free-form fabrication techniques |
| US7705018B2 (en) | 2007-03-23 | 2010-04-27 | Amgen Inc. | Substituted quinolines and their uses in treatment of inflammatory and related conditions |
| EP2211615A4 (en) | 2007-10-22 | 2010-10-13 | Glaxosmithkline Llc | PYRIDOSULFONAMIDE DERIVATIVES AS PI3 KINASE INHIBITORS |
| WO2011111880A1 (ko) | 2010-03-08 | 2011-09-15 | 주식회사 메디젠텍 | 세포핵에서 세포질로의 gsk3의 이동을 억제하는 화합물을 함유하는 세포핵에서 세포질로의 gsk3 이동에 의해 발생되는 질환의 치료 또는 예방용 약학적 조성물 |
| GB201305668D0 (en) * | 2013-03-28 | 2013-05-15 | Glaxosmithkline Ip Dev Ltd | Avs6 Integrin Antagonists |
| WO2015048819A1 (en) | 2013-09-30 | 2015-04-02 | The Regents Of The University Of California | Anti-alphavbeta1 integrin compounds and methods |
| GB201417011D0 (en) * | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417018D0 (en) * | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417094D0 (en) * | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417002D0 (en) * | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| EP3925959A1 (en) | 2015-02-19 | 2021-12-22 | OcuTerra Therapeutics, Inc. | Fluorinated derivatives of 3-(2-oxo-3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)imidazolidin-1-yl)propanoic acid and uses thereof |
| CA2981371A1 (en) | 2015-03-10 | 2016-09-15 | The Regents Of The University Of California | Anti-alphavbeta1 integrin inhibitors and methods of use |
| GB201604589D0 (en) | 2016-03-18 | 2016-05-04 | Glaxosmithkline Ip Dev Ltd | Chemical compound |
| GB201604680D0 (en) | 2016-03-21 | 2016-05-04 | Glaxosmithkline Ip Dev Ltd | Chemical Compounds |
| GB201604681D0 (en) | 2016-03-21 | 2016-05-04 | Glaxosmithkline Ip Dev Ltd | Chemical Compounds |
-
2014
- 2014-09-26 GB GBGB1417094.8A patent/GB201417094D0/en not_active Ceased
-
2015
- 2015-09-22 RU RU2017114355A patent/RU2692775C2/ru not_active IP Right Cessation
- 2015-09-22 WO PCT/EP2015/071782 patent/WO2016046230A1/en not_active Ceased
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- 2015-09-22 US US15/514,416 patent/US10144733B2/en not_active Expired - Fee Related
- 2015-09-22 BR BR112017006242A patent/BR112017006242A2/pt not_active Application Discontinuation
- 2015-09-22 CN CN201580052204.2A patent/CN107074851B/zh not_active Expired - Fee Related
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-
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001024797A1 (en) * | 1999-10-04 | 2001-04-12 | Merck & Co., Inc. | Integrin receptor antagonists |
| RU2296764C2 (ru) * | 2001-11-05 | 2007-04-10 | Новартис Аг | Производные нафтиридина, способ их получения и применение |
| WO2005082889A1 (en) * | 2004-02-18 | 2005-09-09 | Janssen Pharmaceutica N.V. | Piperidinyl targeting compounds that selectively bind integrins |
| RU2481347C2 (ru) * | 2007-08-01 | 2013-05-10 | Валеант Фармасьютикалс Интернэшнл | Производные нафтиридина в качестве модуляторов калиевых каналов |
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| EP3197894A1 (en) | 2017-08-02 |
| US20170291899A1 (en) | 2017-10-12 |
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| KR20170053638A (ko) | 2017-05-16 |
| CN107074851B (zh) | 2020-01-10 |
| AU2015320863B2 (en) | 2018-09-06 |
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| US20190048005A1 (en) | 2019-02-14 |
| CA2962321A1 (en) | 2016-03-31 |
| BR112017006242A2 (pt) | 2017-12-12 |
| GB201417094D0 (en) | 2014-11-12 |
| EP3197894B1 (en) | 2020-06-03 |
| RU2017114355A (ru) | 2018-10-29 |
| US10513517B2 (en) | 2019-12-24 |
| CN107074851A (zh) | 2017-08-18 |
| RU2017114355A3 (enExample) | 2019-01-14 |
| JP6657196B2 (ja) | 2020-03-04 |
| WO2016046230A1 (en) | 2016-03-31 |
| US10144733B2 (en) | 2018-12-04 |
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