PE20230612A1 - Nuevos inhibidores macrociclicos de la quinasa de lrrk2 - Google Patents
Nuevos inhibidores macrociclicos de la quinasa de lrrk2Info
- Publication number
- PE20230612A1 PE20230612A1 PE2022002552A PE2022002552A PE20230612A1 PE 20230612 A1 PE20230612 A1 PE 20230612A1 PE 2022002552 A PE2022002552 A PE 2022002552A PE 2022002552 A PE2022002552 A PE 2022002552A PE 20230612 A1 PE20230612 A1 PE 20230612A1
- Authority
- PE
- Peru
- Prior art keywords
- group
- atom
- disease
- halogen
- nitrogen atom
- Prior art date
Links
Classifications
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- 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
- C07D498/12—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 three hetero rings
- C07D498/18—Bridged 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
- C07D498/12—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 three hetero rings
- C07D498/16—Peri-condensed systems
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
-
- 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
- C07D498/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/18—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Compuesto macrociclico de formula (I), en donde: R es un atomo de hidrogeno, un atomo de halogeno o un grupo alquilo; Z1, Z2 y Z3 son un atomo de carbono o de nitrogeno, entendiendose que el ciclo de 6 miembros que contiene Z1, Z2 y Z3 puede tener 0, 1 o 2 atomos de nitrogeno; X1 esta ausente o es -O-, -S-, o -N(R'a)-, en donde R'a representa un atomo de hidrogeno o un grupo alquilo; X2 es un grupo alcanodiilo sustituido opcionalmente con halogeno, grupo polihalogenoalquilo, grupo alcoxi, grupo hidroxi, grupo amino, entre otros; X3 es un grupo alcanodiilo sustituido opcionalmente con halogeno, grupo polihalogenoalquilo, grupo alcoxi, grupo hidroxi, grupo amino, entre otros; Ra es hidrogeno o un grupo alquilo; A es un grupo ciclico aromatico o parcialmente hidrogenado de la formula (a) o (b), donde A1 y A4 son un atomo de carbono o un atomo de nitrogeno; A2, A3 y A5 son un atomo de carbono, un atomo de oxigeno, un atomo de azufre o un atomo de nitrogeno; A'1, A'2, A'3 y A'4 son un atomo de carbono o un atomo de nitrogeno; significa que el enlace esta unido a X3, estando el grupo ciclico aromatico o parcialmente hidrogenado A sustituido opcionalmente con halogeno, grupo alquilo, grupo alcoxi, grupo hidroxi, grupo oxo, grupo alcoxialquilo, grupo alcoxialcoxi, entre otros. Son compuestos preferidos: 8,14?dioxa?4,10,19,20?tetraazatetraciclo[13.5.2.12,6.018,21]tricosa? 1(20),2,4,6(23),15,17, 21?heptaen?9?ona; - 10?metil?8,14?dioxa?4,10,19,20?tetraazatetraciclo[13.5.2.12,6.018,21]tricosa? 1(20),2,4, 6(23),15,17,21?heptaen?9?ona; entre otros. Dichos compuestos son inhibidores de quinasas, en particular, inhibidores de LRRK2 (Quinasa con Repeticiones Ricas en Leucina 2) y son utiles en el tratamiento y/o diagnostico de enfermedades afectadas o moduladas por la actividad de la quinasa LRRK2 tales como trastornos neurologicos incluyendo la enfermedad de Parkinson y la enfermedad de Alzheimer, enfermedades cardiacas o trastornos inflamatorios tales como la enfermedad de Crohn.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP20315236 | 2020-05-06 | ||
| EP21305112 | 2021-01-28 | ||
| PCT/EP2021/061827 WO2021224320A1 (en) | 2020-05-06 | 2021-05-05 | New macrocyclic lrrk2 kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20230612A1 true PE20230612A1 (es) | 2023-04-13 |
Family
ID=75746649
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2022002552A PE20230612A1 (es) | 2020-05-06 | 2021-05-05 | Nuevos inhibidores macrociclicos de la quinasa de lrrk2 |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US20230357269A1 (es) |
| EP (1) | EP4146658A1 (es) |
| JP (1) | JP2023523863A (es) |
| KR (1) | KR20230006560A (es) |
| CN (1) | CN115996932A (es) |
| AU (1) | AU2021267691A1 (es) |
| BR (1) | BR112022022511A2 (es) |
| CA (1) | CA3182162A1 (es) |
| CL (1) | CL2022003070A1 (es) |
| CO (1) | CO2022015871A2 (es) |
| CR (1) | CR20220561A (es) |
| DO (1) | DOP2022000242A (es) |
| IL (1) | IL297867A (es) |
| MX (1) | MX2022013861A (es) |
| PE (1) | PE20230612A1 (es) |
| TW (1) | TW202208379A (es) |
| UY (1) | UY39199A (es) |
| WO (1) | WO2021224320A1 (es) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7519463B2 (ja) | 2020-05-05 | 2024-07-19 | ヌバレント， インク． | ヘテロ芳香族大環状エーテル化学療法剤 |
| KR20230152654A (ko) | 2020-12-30 | 2023-11-03 | 타이라 바이오사이언시스, 인크. | 키나아제 억제제로서의 인다졸 화합물 |
| MX2023010910A (es) * | 2021-03-18 | 2023-09-27 | Servier Lab | Nuevos inhibidores macrociclicos de la quinasa de lrrk2. |
| CA3231813A1 (en) | 2021-10-01 | 2023-04-06 | Sibao CHEN | Solid forms, pharmaceutical compositions and preparation of heteroaromatic macrocyclic ether compounds |
| CN117425660A (zh) * | 2022-05-18 | 2024-01-19 | 上海翊石医药科技有限公司 | 一种芳杂环类化合物及其中间体、药物组合物和用途 |
| TW202413377A (zh) * | 2022-06-08 | 2024-04-01 | 美商榮山醫藥股份有限公司 | 吲唑巨環化合物及其用途 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX342177B (es) * | 2011-09-30 | 2016-09-20 | Ipsen Pharma Sas | Inhibidores de cinasa 2 de repeticion rica en leucina (lrrk2) macrociclica. |
| US9718818B2 (en) * | 2013-08-22 | 2017-08-01 | Merck Sharp & Dohme Corp. | Compounds inhibiting leucine-rich repeat kinase enzyme activity |
| WO2016042089A1 (en) | 2014-09-17 | 2016-03-24 | Oncodesign S.A. | Macrocyclic lrrk2 kinase inhibitors |
| US10608658B2 (en) | 2016-07-04 | 2020-03-31 | Telefonaktiebolaget Lm Ericsson (Publ) | Pipelined analog-to-digital converter |
| CA3049820A1 (en) | 2017-01-25 | 2018-08-02 | Glaxosmithkline Intellectual Property Development Limited | Compounds for inhibiting lrrk2 kinase activity |
| EP3587422A4 (en) | 2017-02-22 | 2020-05-06 | Daegu-Gyeongbuk Medical Innovation Foundation | PYRROLO-PYRIMIDINE DERIVATIVE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION COMPRISING SAME AS ACTIVE INGREDIENT FOR THE PREVENTION OR TREATMENT OF A PROTEIN KINASE-RELATED DISEASE |
| AU2018230236B2 (en) | 2017-03-10 | 2022-05-19 | Pfizer Inc. | Novel imidazo[4,5-c]quinoline derivatives as LRRK2 inhibitors |
| WO2018217946A1 (en) | 2017-05-24 | 2018-11-29 | Denali Therapeutics Inc. | Compounds, compositions and methods |
| EP3652179A1 (en) | 2017-07-14 | 2020-05-20 | GlaxoSmithKline Intellectual Property Development Ltd | Inhibitors of leucine rich repeat kinase 2 |
| WO2019074809A1 (en) | 2017-10-11 | 2019-04-18 | Merck Sharp & Dohme Corp. | INDAZOLYL-SPIRO [2.2] PENTANE-CARBONITRILE DERIVATIVES AS LRRK2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF |
| KR20200085779A (ko) | 2017-12-05 | 2020-07-15 | 주식회사 오스코텍 | Lrrk2 억제제로서의 피롤로(피라졸로)피리미딘 유도체 |
| WO2019222173A1 (en) | 2018-05-15 | 2019-11-21 | E-Scape Bio, Inc. | Fused tetrazoles as lrrk2 inhibitors |
| WO2019241540A1 (en) * | 2018-06-15 | 2019-12-19 | Samumed, Llc | Indazole containing macrocycles and therapeutic uses thereof |
| TWI833770B (zh) | 2018-06-27 | 2024-03-01 | 美商Ionis製藥公司 | 用於減少 lrrk2 表現之化合物及方法 |
-
2021
- 2021-05-05 BR BR112022022511A patent/BR112022022511A2/pt unknown
- 2021-05-05 CA CA3182162A patent/CA3182162A1/en active Pending
- 2021-05-05 WO PCT/EP2021/061827 patent/WO2021224320A1/en active Application Filing
- 2021-05-05 PE PE2022002552A patent/PE20230612A1/es unknown
- 2021-05-05 CR CR20220561A patent/CR20220561A/es unknown
- 2021-05-05 MX MX2022013861A patent/MX2022013861A/es unknown
- 2021-05-05 IL IL297867A patent/IL297867A/en unknown
- 2021-05-05 US US17/923,002 patent/US20230357269A1/en active Pending
- 2021-05-05 AU AU2021267691A patent/AU2021267691A1/en active Pending
- 2021-05-05 TW TW110116241A patent/TW202208379A/zh unknown
- 2021-05-05 KR KR1020227042327A patent/KR20230006560A/ko active Search and Examination
- 2021-05-05 EP EP21722503.6A patent/EP4146658A1/en active Pending
- 2021-05-05 CN CN202180044443.9A patent/CN115996932A/zh active Pending
- 2021-05-05 JP JP2022567124A patent/JP2023523863A/ja active Pending
- 2021-05-06 UY UY0001039199A patent/UY39199A/es unknown
-
2022
- 2022-11-02 DO DO2022000242A patent/DOP2022000242A/es unknown
- 2022-11-03 CO CONC2022/0015871A patent/CO2022015871A2/es unknown
- 2022-11-04 CL CL2022003070A patent/CL2022003070A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20230006560A (ko) | 2023-01-10 |
| UY39199A (es) | 2021-11-30 |
| CA3182162A1 (en) | 2021-11-11 |
| JP2023523863A (ja) | 2023-06-07 |
| MX2022013861A (es) | 2023-02-22 |
| CR20220561A (es) | 2023-02-17 |
| CN115996932A (zh) | 2023-04-21 |
| BR112022022511A2 (pt) | 2022-12-13 |
| AU2021267691A1 (en) | 2022-12-08 |
| CL2022003070A1 (es) | 2023-07-07 |
| TW202208379A (zh) | 2022-03-01 |
| US20230357269A1 (en) | 2023-11-09 |
| WO2021224320A1 (en) | 2021-11-11 |
| CO2022015871A2 (es) | 2022-12-30 |
| DOP2022000242A (es) | 2023-07-31 |
| EP4146658A1 (en) | 2023-03-15 |
| IL297867A (en) | 2023-01-01 |
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