CO2021006837A2 - Derivados de 7-fenoxi-n-(3-azabiciclo[3.2.1]octan-8-il)-6,7-dihidro-5h-pirrolo[1,2-b][1,2,4]triazol-2-amina y compuestos relacionados como moduladores de gamma-secretasa para el tratamiento de la enfermedad de alzheimer - Google Patents
Derivados de 7-fenoxi-n-(3-azabiciclo[3.2.1]octan-8-il)-6,7-dihidro-5h-pirrolo[1,2-b][1,2,4]triazol-2-amina y compuestos relacionados como moduladores de gamma-secretasa para el tratamiento de la enfermedad de alzheimerInfo
- Publication number
- CO2021006837A2 CO2021006837A2 CONC2021/0006837A CO2021006837A CO2021006837A2 CO 2021006837 A2 CO2021006837 A2 CO 2021006837A2 CO 2021006837 A CO2021006837 A CO 2021006837A CO 2021006837 A2 CO2021006837 A2 CO 2021006837A2
- Authority
- CO
- Colombia
- Prior art keywords
- compounds
- octan
- azabicyclo
- pyrrolo
- triazol
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title abstract 7
- VHNYOQKVZQVBLC-RTCGXNAVSA-N (4r,7e,9as)-7-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]-4-(3,4,5-trifluorophenyl)-1,3,4,8,9,9a-hexahydropyrido[2,1-c][1,4]oxazin-6-one Chemical compound C1([C@@H]2COC[C@@H]3CC\C(C(N32)=O)=C/C=2C=C(C(=CC=2)N2C=C(C)N=C2)OC)=CC(F)=C(F)C(F)=C1 VHNYOQKVZQVBLC-RTCGXNAVSA-N 0.000 title abstract 2
- 208000024827 Alzheimer disease Diseases 0.000 title abstract 2
- 229940124648 γ-Secretase Modulator Drugs 0.000 title abstract 2
- -1 3-azabicyclo [3.2.1] octan-8-yl Chemical group 0.000 abstract 2
- 238000000034 method Methods 0.000 abstract 2
- 208000024667 ABeta amyloidosis, Dutch type Diseases 0.000 abstract 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 abstract 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 abstract 1
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 abstract 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 abstract 1
- 206010011878 Deafness Diseases 0.000 abstract 1
- 206010012289 Dementia Diseases 0.000 abstract 1
- 201000010374 Down Syndrome Diseases 0.000 abstract 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 abstract 1
- 201000004810 Vascular dementia Diseases 0.000 abstract 1
- 206010002022 amyloidosis Diseases 0.000 abstract 1
- 210000004556 brain Anatomy 0.000 abstract 1
- 238000013329 compounding Methods 0.000 abstract 1
- 230000008021 deposition Effects 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 208000036536 dutch type ABeta amyloidosis Diseases 0.000 abstract 1
- 230000010370 hearing loss Effects 0.000 abstract 1
- 231100000888 hearing loss Toxicity 0.000 abstract 1
- 208000016354 hearing loss disease Diseases 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- 208000012005 synaptopathy Diseases 0.000 abstract 1
- BDJWKDVEYUXIRO-UHFFFAOYSA-N triazol-2-amine Chemical compound NN1N=CC=N1 BDJWKDVEYUXIRO-UHFFFAOYSA-N 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—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
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P27/16—Otologicals
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
La invención proporciona derivados de 7-fenoxi-N-(3-azabiciclo[3.2.1]octan-8-il)-6,7-dihidro-5H-pirrolo[1,2-b][1,2,4]triazol-2-amina y compuestos relacionados de la fórmula general (I) en donde R1, Ar, n y m son como se describen en la presente, composiciones que incluyen los compuestos, procesos de elaboración de los compuestos y los compuestos para su uso en los métodos de tratamiento médico. Los presentes compuestos son como moduladores de gamma-secretasa para el tratamiento de enfermedades asociadas al depósito de β-amiloide en el cerebro, tales como enfermedad de Alzheimer, angiopatía amiloide cerebral, sinaptopatía coclear, hipoacusia, hemorragia cerebral hereditaria con amiloidosis de tipo holandés (HCHWA-D), demencia multiinfarto, demencia pugilística y síndrome de Down. La presente descripción divulga la preparación de compuestos de ejemplo así como los datos farmacológicos de estos (por ejemplo, las páginas 54 a 74; los ejemplos 1 a 64; tabla). Un compuesto de ejemplo es, por ejemplo, (R)-7-(3,5-difluorofenoxi)-N-((1R,5S,8s)-3-(6-metoxipiridazin-4-il)-3-azabiciclo[3.2.1]octan-8-il)-6,7-dihidro-5H-pirrolo[1,2-b][1,2,4]triazol-2-amina (ejemplo 1).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP18212199 | 2018-12-13 | ||
| PCT/EP2019/084538 WO2020120521A1 (en) | 2018-12-13 | 2019-12-11 | 7-phenoxy-n-(3-azabicyclo[3.2.1]octan-8-yl)-6,7-dihydro-5h-pyrrolo[1,2-b][1,2,4]triazol-2-amine derivatives and related compounds as gamma-secretase modulators for the treatment of alzheimer's disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CO2021006837A2 true CO2021006837A2 (es) | 2021-06-10 |
Family
ID=64665266
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CONC2021/0006837A CO2021006837A2 (es) | 2018-12-13 | 2021-05-24 | Derivados de 7-fenoxi-n-(3-azabiciclo[3.2.1]octan-8-il)-6,7-dihidro-5h-pirrolo[1,2-b][1,2,4]triazol-2-amina y compuestos relacionados como moduladores de gamma-secretasa para el tratamiento de la enfermedad de alzheimer |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US20220056036A1 (es) |
| EP (2) | EP3894411B1 (es) |
| JP (1) | JP7566745B2 (es) |
| KR (1) | KR20210102900A (es) |
| CN (2) | CN113179641B (es) |
| AR (1) | AR116906A1 (es) |
| AU (1) | AU2019395774A1 (es) |
| BR (1) | BR112021009443A2 (es) |
| CA (1) | CA3117870A1 (es) |
| CL (1) | CL2021001547A1 (es) |
| CO (1) | CO2021006837A2 (es) |
| CR (1) | CR20210305A (es) |
| DK (1) | DK3894411T3 (es) |
| FI (1) | FI3894411T3 (es) |
| IL (2) | IL283823B2 (es) |
| LT (1) | LT3894411T (es) |
| MA (1) | MA54447A (es) |
| MX (1) | MX2021006761A (es) |
| PE (1) | PE20211776A1 (es) |
| PL (1) | PL3894411T3 (es) |
| PT (1) | PT3894411T (es) |
| RS (1) | RS65821B1 (es) |
| SG (1) | SG11202103340PA (es) |
| TW (1) | TWI831892B (es) |
| WO (1) | WO2020120521A1 (es) |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8703763B2 (en) * | 2011-03-02 | 2014-04-22 | Hoffmann-La Roche Inc. | Bridged piperidine derivatives |
| WO2017042114A1 (en) | 2015-09-09 | 2017-03-16 | F. Hoffmann-La Roche Ag | Bridged piperidine derivatives |
| CN108137579B (zh) * | 2015-12-10 | 2022-01-07 | 豪夫迈·罗氏有限公司 | 桥连哌啶衍生物 |
| WO2018001918A1 (en) * | 2016-06-27 | 2018-01-04 | F. Hoffmann-La Roche Ag | Triazolopyridines as gamma-secretase modulators |
| WO2018083050A1 (en) * | 2016-11-01 | 2018-05-11 | F. Hoffmann-La Roche Ag | Bicyclic heteroaryl derivatives |
| CN109790149B (zh) | 2016-11-08 | 2022-05-17 | 豪夫迈·罗氏有限公司 | 苯氧基三唑类化合物 |
| RU2757276C2 (ru) | 2016-12-16 | 2021-10-12 | Пайплайн Терапьютикс, Инк. | Способы лечения кохлеарной синаптопатии |
| US11370802B2 (en) | 2018-01-22 | 2022-06-28 | Hoffmann-La Roche, Inc. | Triazolo-azepine derivatives |
-
2019
- 2019-12-11 KR KR1020217017774A patent/KR20210102900A/ko unknown
- 2019-12-11 JP JP2021533563A patent/JP7566745B2/ja active Active
- 2019-12-11 AU AU2019395774A patent/AU2019395774A1/en active Pending
- 2019-12-11 MX MX2021006761A patent/MX2021006761A/es unknown
- 2019-12-11 SG SG11202103340PA patent/SG11202103340PA/en unknown
- 2019-12-11 PE PE2021000726A patent/PE20211776A1/es unknown
- 2019-12-11 PL PL19824250.5T patent/PL3894411T3/pl unknown
- 2019-12-11 EP EP19824250.5A patent/EP3894411B1/en active Active
- 2019-12-11 PT PT198242505T patent/PT3894411T/pt unknown
- 2019-12-11 DK DK19824250.5T patent/DK3894411T3/da active
- 2019-12-11 CN CN201980076253.8A patent/CN113179641B/zh active Active
- 2019-12-11 CN CN202311792520.6A patent/CN117946116A/zh active Pending
- 2019-12-11 US US17/413,413 patent/US20220056036A1/en active Pending
- 2019-12-11 CA CA3117870A patent/CA3117870A1/en active Pending
- 2019-12-11 IL IL283823A patent/IL283823B2/en unknown
- 2019-12-11 EP EP24177200.3A patent/EP4424370A2/en active Pending
- 2019-12-11 CR CR20210305A patent/CR20210305A/es unknown
- 2019-12-11 LT LTEPPCT/EP2019/084538T patent/LT3894411T/lt unknown
- 2019-12-11 MA MA054447A patent/MA54447A/fr unknown
- 2019-12-11 RS RS20240883A patent/RS65821B1/sr unknown
- 2019-12-11 WO PCT/EP2019/084538 patent/WO2020120521A1/en active Application Filing
- 2019-12-11 FI FIEP19824250.5T patent/FI3894411T3/fi active
- 2019-12-11 IL IL310081A patent/IL310081A/en unknown
- 2019-12-11 BR BR112021009443-1A patent/BR112021009443A2/pt unknown
- 2019-12-12 AR ARP190103631A patent/AR116906A1/es unknown
- 2019-12-12 TW TW108145480A patent/TWI831892B/zh active
-
2021
- 2021-05-24 CO CONC2021/0006837A patent/CO2021006837A2/es unknown
- 2021-06-11 CL CL2021001547A patent/CL2021001547A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL283823B2 (en) | 2024-07-01 |
| EP4424370A2 (en) | 2024-09-04 |
| CL2021001547A1 (es) | 2021-12-24 |
| BR112021009443A2 (pt) | 2021-08-17 |
| IL310081A (en) | 2024-03-01 |
| EP3894411A1 (en) | 2021-10-20 |
| TW202039499A (zh) | 2020-11-01 |
| TWI831892B (zh) | 2024-02-11 |
| RS65821B1 (sr) | 2024-09-30 |
| PT3894411T (pt) | 2024-08-08 |
| IL283823A (en) | 2021-07-29 |
| SG11202103340PA (en) | 2021-04-29 |
| MA54447A (fr) | 2022-03-23 |
| IL283823B1 (en) | 2024-03-01 |
| CN113179641A (zh) | 2021-07-27 |
| FI3894411T3 (fi) | 2024-08-15 |
| CA3117870A1 (en) | 2020-06-18 |
| LT3894411T (lt) | 2024-08-26 |
| US20220056036A1 (en) | 2022-02-24 |
| CN117946116A (zh) | 2024-04-30 |
| JP2022513466A (ja) | 2022-02-08 |
| MX2021006761A (es) | 2021-07-15 |
| CR20210305A (es) | 2021-07-20 |
| DK3894411T3 (da) | 2024-08-19 |
| EP3894411B1 (en) | 2024-06-19 |
| JP7566745B2 (ja) | 2024-10-15 |
| PE20211776A1 (es) | 2021-09-08 |
| CN113179641B (zh) | 2024-01-02 |
| PL3894411T3 (pl) | 2024-10-07 |
| AR116906A1 (es) | 2021-06-23 |
| KR20210102900A (ko) | 2021-08-20 |
| AU2019395774A1 (en) | 2021-04-08 |
| WO2020120521A1 (en) | 2020-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ECSP14013221A (es) | Fenil-3-aza-biciclo [3.1.0] hex-3-il-metanonas y su uso como medicamento. | |
| ES2939260T3 (es) | Derivado de gamma-aminoácido tricíclico condensado, método de preparación del mismo y uso médico del mismo | |
| AR096371A1 (es) | 2-fenilimidazo[1,2-a]pirimidinas | |
| AR107928A1 (es) | Moduladores alostéricos de receptores de acetilcolina nicotínicos | |
| NI201600166A (es) | Compuestos de imidazo[4, 5-c]quinolin-2-ona y su uso para tratar cáncer | |
| AR100713A1 (es) | Derivados de amida de compuestos de 1-oxa-4,9-diazaespiro undeceno que tienen actividad multimodal contra el dolor | |
| PH12015501878A1 (en) | Tetrahydroimidazo[1,5-d][1,4]oxazepine derivative | |
| ECSP13012891A (es) | Derivados de heteroarilo como moduladores de nachr alfa 7 | |
| DOP2012000067A (es) | Compuestos de dióxido de iminotiadiazina como inhibidores de enzima de disociacion de app de sitio beta ( bace), composiciones, y su uso | |
| BR112017022568A2 (pt) | compostos e seus usos como inibidores de bace1 | |
| BR112022005674A2 (pt) | Derivado de anel fundido aromático substituído e composição compreendendo o mesmo, e uso do mesmo | |
| SI2875011T1 (en) | 5-HT3 receptor antagonists | |
| AR087915A1 (es) | N-(3-(2-amino-6,6-difluor-4,4a,5,6,7,7a-hexahidro-ciclopenta-[e][1,3]oxazin-4-il)-fenil)-amidas como inhibidores de la bace1 | |
| AR100715A1 (es) | Derivados de alquilo de compuestos 1-oxa-4,9-diazaespiro undeceno que tienen actividad multimodal contra el dolor | |
| AR081154A1 (es) | Compuestos de amino-oxazinas y amino-dihidrotiazina como moduladores de beta-secretasa y metodos de uso | |
| BR112013025128A2 (pt) | derivados de pirrol como moduladores de receptor de acetilcolina nicotínico para uso no tratamento de distúrbios neurodegenenerativos tal como doença de alzheimer e doença de parkinson | |
| AR086036A1 (es) | DERIVADOS DE ETINILO COMO MODULADORES ALOSTERICOS POSITIVOS DE (mGluR5) | |
| CL2022001741A1 (es) | Compuestos cíclicos y métodos de uso de estos | |
| CO2021014223A2 (es) | Nuevos compuestos y composiciones farmacéuticas de los mismos para el tratamiento de trastornos inflamatorios | |
| AR096119A1 (es) | Derivados 2-fenil- o 2- hetaril-imidazol[1,2-a]piridina | |
| AR115065A1 (es) | Moduladores alostéricos de espiropiperidina de receptores nicotínicos de acetilcolina | |
| AR064739A1 (es) | Compuesto de [1,2,3] -benzotriazinona-3- sustituido para mejorar las respuestas sinapticas glutamatergicas | |
| PE20212113A1 (es) | Inhibidores de moleculas pequenas de la familia de quinasas jak | |
| CL2013003646A1 (es) | Compuestos derivados de trans-1-(3s.1r)-6-cloro-3-fenilindan-1-il)-1,2,2-trimetilpiperazina deuterados, con actividad en los receptores 5ht2, d1 y d2; proceso de preparacion; compuesto intermediario; composicion y combinacion farmaceutica; y su uso para el tratamiento de la psicosis, entre otros. | |
| CO6341621A2 (es) | Piperidinas arilamino y heteroarilamino sustituidas como inhibidores de glyt-1 |