PE20230612A1 - Nuevos inhibidores macrociclicos de la quinasa de lrrk2 - Google Patents

Nuevos inhibidores macrociclicos de la quinasa de lrrk2

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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
Application number
PE2022002552A
Other languages
English (en)
Inventor
Petra Marcella Blom
Christopher Gaetan Housseman
Alain Daugan
Audrey Dumoulin
Maxime Laugeois
Alexis Denis
Nicolas Faucher
Iuliana Botez
Tiran Arnaud Le
Kenneth Christensen
Yann Lamotte
Original Assignee
Servier Lab
Oncodesign Prec Medicine Opm
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Servier Lab, Oncodesign Prec Medicine Opm filed Critical Servier Lab
Publication of PE20230612A1 publication Critical patent/PE20230612A1/es

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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
    • 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.
PE2022002552A 2020-05-06 2021-05-05 Nuevos inhibidores macrociclicos de la quinasa de lrrk2 PE20230612A1 (es)

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 (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3213388A1 (en) * 2021-03-18 2022-09-22 Les Laboratoires Servier Macrocyclic lrrk2 kinase inhibitors
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
WO2023240140A1 (en) * 2022-06-08 2023-12-14 Blossomhill Therapeutics, Inc. Indazole macrocycles and their use

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUE029728T2 (en) * 2011-09-30 2017-03-28 Ipsen Pharma Sas Macrocyclic LRRK2 kinase inhibitors
US9718818B2 (en) * 2013-08-22 2017-08-01 Merck Sharp & Dohme Corp. Compounds inhibiting leucine-rich repeat kinase enzyme activity
PL3194405T4 (pl) 2014-09-17 2019-07-31 Oncodesign S.A. Makrocykliczne inhibitory kinazy lrrk2
US10608658B2 (en) 2016-07-04 2020-03-31 Telefonaktiebolaget Lm Ericsson (Publ) Pipelined analog-to-digital converter
BR112019015314A2 (pt) 2017-01-25 2020-05-19 Glaxosmithkline Ip Dev Ltd compostos para inibir a atividade da quinase lrrk2
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
BR112019018688A2 (pt) 2017-03-10 2020-04-07 Pfizer derivados de imidazo[4,5-c] quinolina como inibidores de lrrk2
WO2018217946A1 (en) 2017-05-24 2018-11-29 Denali Therapeutics Inc. Compounds, compositions and methods
BR112020000772A2 (pt) 2017-07-14 2020-07-21 Glaxosmithkline Intellectual Property Development Limited inibidores de cinase 2 de repetição rica em leucina
US11161854B2 (en) 2017-10-11 2021-11-02 Merck Sharp & Dohme Corp. Indazolyl-spiro[2.2]pentane-carbonitrile derivatives as LRRK2 inhibitors, pharmaceutical compositions, and uses thereof
US11370796B2 (en) 2017-12-05 2022-06-28 Oscotec Inc. Substituted pyrazoles as LRRK2 inhibitors
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

Also Published As

Publication number Publication date
WO2021224320A1 (en) 2021-11-11
IL297867A (en) 2023-01-01
UY39199A (es) 2021-11-30
CN115996932A (zh) 2023-04-21
CA3182162A1 (en) 2021-11-11
EP4146658A1 (en) 2023-03-15
US20230357269A1 (en) 2023-11-09
BR112022022511A2 (pt) 2022-12-13
CO2022015871A2 (es) 2022-12-30
DOP2022000242A (es) 2023-07-31
JP2023523863A (ja) 2023-06-07
CL2022003070A1 (es) 2023-07-07
MX2022013861A (es) 2023-02-22
AU2021267691A1 (en) 2022-12-08
CR20220561A (es) 2023-02-17
KR20230006560A (ko) 2023-01-10
TW202208379A (zh) 2022-03-01

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