MX349556B - Derivados de aminopirimidina como moduladores de proteina cinasa 2 rica en unidades repetitivas de leucina (lrrk2). - Google Patents

Derivados de aminopirimidina como moduladores de proteina cinasa 2 rica en unidades repetitivas de leucina (lrrk2).

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Publication number
MX349556B
MX349556B MX2014006026A MX2014006026A MX349556B MX 349556 B MX349556 B MX 349556B MX 2014006026 A MX2014006026 A MX 2014006026A MX 2014006026 A MX2014006026 A MX 2014006026A MX 349556 B MX349556 B MX 349556B
Authority
MX
Mexico
Prior art keywords
aminopyrimidine derivatives
compounds
lrrk2 modulators
lrrk2
modulators
Prior art date
Application number
MX2014006026A
Other languages
English (en)
Other versions
MX2014006026A (es
Inventor
Chen Huifen
baker glenn Charles
Chambers Mark
K Chan Bryan
Estrada Anthony
Shore Daniel
Sweeney Zachary
Original Assignee
Genentech Inc
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 Genentech Inc filed Critical Genentech Inc
Publication of MX2014006026A publication Critical patent/MX2014006026A/es
Publication of MX349556B publication Critical patent/MX349556B/es

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    • 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
    • C07D413/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D405/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • 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
    • C07D405/10—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 linked by a carbon chain containing aromatic rings

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Se describen en la presente, los compuestos de la fórmula (I), o las sales farmacéuticamente aceptables de los mismos, en donde m, n. X, R1, R2, R3, R4 y R5 son como se definen en la presente. Se describen también los métodos para la elaboración de los compuestos y el uso de los compuestos para el tratamiento de los trastornos asociados con el receptor de LRRK2, tal como la enfermedad de Parkinson.
MX2014006026A 2011-11-29 2012-11-28 Derivados de aminopirimidina como moduladores de proteina cinasa 2 rica en unidades repetitivas de leucina (lrrk2). MX349556B (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161564753P 2011-11-29 2011-11-29
PCT/EP2012/073761 WO2013079493A1 (en) 2011-11-29 2012-11-28 Aminopyrimidine derivatives as lrrk2 modulators

Publications (2)

Publication Number Publication Date
MX2014006026A MX2014006026A (es) 2014-06-04
MX349556B true MX349556B (es) 2017-08-03

Family

ID=47297198

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MX2014006026A MX349556B (es) 2011-11-29 2012-11-28 Derivados de aminopirimidina como moduladores de proteina cinasa 2 rica en unidades repetitivas de leucina (lrrk2).

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Country Link
US (1) US9145402B2 (es)
EP (1) EP2807152B1 (es)
JP (1) JP6117816B2 (es)
KR (1) KR102002198B1 (es)
CN (1) CN103958482B (es)
BR (1) BR112014011850B1 (es)
CA (1) CA2852609C (es)
ES (1) ES2638595T3 (es)
MX (1) MX349556B (es)
RU (1) RU2634716C2 (es)
WO (1) WO2013079493A1 (es)

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HUE029196T2 (en) * 2010-06-04 2017-02-28 Hoffmann La Roche Aminoprimidine derivatives as LRRK2 modulators
SG189043A1 (en) * 2010-11-10 2013-05-31 Hoffmann La Roche Pyrazole aminopyrimidine derivatives as lrrk2 modulators
US8791130B2 (en) * 2011-11-29 2014-07-29 Genentech, Inc. Aminopyrimidine derivatives as LRRK2 modulators
AR089182A1 (es) * 2011-11-29 2014-08-06 Hoffmann La Roche Derivados de aminopirimidina como moduladores de lrrk2
CA2850594C (en) * 2011-11-29 2020-03-10 F. Hoffmann-La Roche Ag Aminopyrimidine derivatives as lrrk2 modulators
EP2844658B1 (en) * 2012-05-03 2019-03-20 Genentech, Inc. Pyrazole aminopyrimidine derivatives as lrrk2 modulators for use in the treatment of parkinson's disease
WO2017156493A1 (en) 2016-03-11 2017-09-14 Denali Therapeutics Inc. Compounds, compositions, and methods
WO2014134772A1 (en) * 2013-03-04 2014-09-12 Merck Sharp & Dohme Corp. Compounds inhibiting leucine-rich repeat kinase enzyme activity
US10004751B2 (en) 2014-07-10 2018-06-26 The J. David Gladstone Institutes Compositions and methods for treating Dengue virus infection
WO2016100452A2 (en) * 2014-12-17 2016-06-23 Celgene Avilomics Research, Inc. Heteroaryl compounds and uses thereof
WO2016130920A2 (en) * 2015-02-13 2016-08-18 Dana-Farber Cancer Institute, Inc. Lrrk2 inhibitors and methods of making and using the same
US11214565B2 (en) 2015-11-20 2022-01-04 Denali Therapeutics Inc. Compound, compositions, and methods
SI3472153T1 (sl) 2016-06-16 2022-01-31 Denali Therapeutics Inc. Pirimidin-2-ilamino-1H-pirazoli kot zaviralci LRRK2 za uporabo pri zdravljenju nevrodegenerativnih motenj
AR109179A1 (es) 2016-08-19 2018-11-07 Pfizer Inhibidores de diacilglicerol aciltransferasa 2
PE20210157A1 (es) 2017-11-21 2021-01-26 Denali Therapeutics Inc Polimorfos y formas solidas de un compuesto de pirimidinilamino-pirazol y metodos de produccion
US11834438B2 (en) 2017-12-20 2023-12-05 Denali Therapeutics Inc. Process for the preparation of pyrimidinyl-4-aminopyrazole compounds
AU2020274011B2 (en) 2019-05-10 2024-02-15 Deciphera Pharmaceuticals, Llc Heteroarylaminopyrimidine amide autophagy inhibitors and methods of use thereof
RS65019B1 (sr) 2019-05-10 2024-01-31 Deciphera Pharmaceuticals Llc Fenilaminopirimidin amidni inhibitori autofagije i postupci njihove primene
BR112021024194A2 (pt) * 2019-05-31 2022-01-11 Denali Therapeutics Inc Formulação de liberação modificada de um composto de pirimidinilamino-pirazol e métodos de tratamento
CN119241444A (zh) 2019-06-17 2025-01-03 德西费拉制药有限责任公司 氨基嘧啶酰胺自噬抑制剂及其使用方法
CN110128354A (zh) * 2019-06-20 2019-08-16 大连大学 一种5-氟-2-甲磺酰基-4-氨基嘧啶的制备方法
CN111646978B (zh) * 2020-06-11 2021-12-21 浙江大学 N2-取代烷氧芳环-2-氨基嘧啶类衍生物及应用
WO2022084210A1 (en) 2020-10-20 2022-04-28 F. Hoffmann-La Roche Ag Combination therapy of pd-1 axis binding antagonists and lrrk2 inhitibors
CN116528869A (zh) * 2020-11-27 2023-08-01 安锐生物医药科技(广州)有限公司 氨基杂芳基激酶抑制剂
WO2022216098A1 (ko) * 2021-04-08 2022-10-13 주식회사 스탠다임 신규한 lrrk2 억제제
CN113831321B (zh) * 2021-09-18 2023-01-31 安润医药科技（苏州）有限公司 富亮氨酸重复激酶2的小分子抑制剂及其应用
WO2024097394A1 (en) 2022-11-03 2024-05-10 Denali Therapeutics Inc. Solid and co-crystal forms of a pyrimidine triazole compound
WO2024112746A1 (en) 2022-11-22 2024-05-30 Denali Therapeutics Inc. Processes and intermediates for the preparation of a pyrimidine aminopyrazole compound

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WO2011153553A2 (en) * 2010-06-04 2011-12-08 The Regents Of The University Of California Methods and compositions for kinase inhibition
SG189043A1 (en) 2010-11-10 2013-05-31 Hoffmann La Roche Pyrazole aminopyrimidine derivatives as lrrk2 modulators

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Publication number Publication date
KR102002198B1 (ko) 2019-07-19
KR20140097476A (ko) 2014-08-06
BR112014011850A2 (pt) 2017-05-02
JP6117816B2 (ja) 2017-04-19
US9145402B2 (en) 2015-09-29
MX2014006026A (es) 2014-06-04
WO2013079493A1 (en) 2013-06-06
CN103958482B (zh) 2017-06-09
CN103958482A (zh) 2014-07-30
CA2852609C (en) 2020-03-10
BR112014011850A8 (pt) 2017-07-11
ES2638595T3 (es) 2017-10-23
RU2014124953A (ru) 2016-01-27
JP2015500215A (ja) 2015-01-05
CA2852609A1 (en) 2013-06-26
EP2807152B1 (en) 2017-07-19
BR112014011850B1 (pt) 2022-01-11
EP2807152A1 (en) 2014-12-03
RU2634716C2 (ru) 2017-11-03
US20130158032A1 (en) 2013-06-20

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