CA2754605C - Pyrazolopyridine compounds and their use as lrrk2 inhibitors - Google Patents

Pyrazolopyridine compounds and their use as lrrk2 inhibitors Download PDF

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Publication number
CA2754605C
CA2754605C CA2754605A CA2754605A CA2754605C CA 2754605 C CA2754605 C CA 2754605C CA 2754605 A CA2754605 A CA 2754605A CA 2754605 A CA2754605 A CA 2754605A CA 2754605 C CA2754605 C CA 2754605C
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CA
Canada
Prior art keywords
alkyl
heterocycloalkyl
aryl
optionally substituted
heteroaryl
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Fee Related
Application number
CA2754605A
Other languages
English (en)
French (fr)
Other versions
CA2754605A1 (en
Inventor
Edward Giles Mciver
Ela Smiljanic
Denise Jamilla Harding
Joanne Hough
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LifeArc
Original Assignee
LifeArc
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
Priority claimed from GB0904746A external-priority patent/GB0904746D0/en
Priority claimed from GB0912238A external-priority patent/GB0912238D0/en
Priority claimed from GBGB1001418.1A external-priority patent/GB201001418D0/en
Application filed by LifeArc filed Critical LifeArc
Publication of CA2754605A1 publication Critical patent/CA2754605A1/en
Application granted granted Critical
Publication of CA2754605C publication Critical patent/CA2754605C/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • 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
    • A61K31/437—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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • C07F9/65611—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system (X = CH2, O, S, NH) optionally with an additional double bond and/or substituents, e.g. penicillins and analogs

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (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)
  • Psychology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CA2754605A 2009-03-19 2010-03-19 Pyrazolopyridine compounds and their use as lrrk2 inhibitors Expired - Fee Related CA2754605C (en)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
GB0904746.5 2009-03-19
GB0904746A GB0904746D0 (en) 2009-03-19 2009-03-19 Compounds
US16202409P 2009-03-20 2009-03-20
US61/162,024 2009-03-20
GB0912238A GB0912238D0 (en) 2009-07-14 2009-07-14 Compounds
GB0912238.3 2009-07-14
GBGB1001418.1A GB201001418D0 (en) 2010-01-28 2010-01-28 Compounds
GB1001418.1 2010-01-28
PCT/GB2010/000498 WO2010106333A1 (en) 2009-03-19 2010-03-19 Compounds

Publications (2)

Publication Number Publication Date
CA2754605A1 CA2754605A1 (en) 2010-09-23
CA2754605C true CA2754605C (en) 2018-04-17

Family

ID=42226628

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2754605A Expired - Fee Related CA2754605C (en) 2009-03-19 2010-03-19 Pyrazolopyridine compounds and their use as lrrk2 inhibitors

Country Status (13)

Country Link
US (2) US20100317646A1 (enExample)
EP (1) EP2408772B1 (enExample)
JP (1) JP5732036B2 (enExample)
KR (1) KR101700229B1 (enExample)
CN (1) CN102428084B (enExample)
AU (1) AU2010224693B2 (enExample)
CA (1) CA2754605C (enExample)
CL (1) CL2011002267A1 (enExample)
IL (1) IL215147A0 (enExample)
MX (1) MX2011009807A (enExample)
PE (1) PE20120506A1 (enExample)
RU (1) RU2011142182A (enExample)
WO (1) WO2010106333A1 (enExample)

Families Citing this family (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE602007013573D1 (de) * 2006-08-16 2011-05-12 Hoffmann La Roche Nicht-nukleosidische reverse-transkriptase-hemmer
GB201008134D0 (en) * 2010-05-14 2010-06-30 Medical Res Council Technology Compounds
GB201015949D0 (en) 2010-09-22 2010-11-03 Medical Res Council Technology Compounds
EP2632260A4 (en) * 2010-10-29 2015-06-17 Merck Sharp & Dohme LEUCINREICH REPEAT KINASE ENZYME ACTIVITY
US20130338106A1 (en) * 2011-02-28 2013-12-19 John A. McCauley Compounds inhibiting leucine-rich repeat kinase enzyme activity
WO2012135631A1 (en) * 2011-03-30 2012-10-04 Arrien Pharmaeuticals Llc Substituted 5-(pyrazin-2-yl)-1h-pyrazolo [3, 4-b] pyridine and pyrazolo [3, 4-b] pyridine derivatives as protein kinase inhibitors
TWI557121B (zh) * 2011-04-21 2016-11-11 原真股份有限公司 新穎激酶抑制劑
WO2012162254A1 (en) 2011-05-23 2012-11-29 Elan Pharmaceuticals, Inc. Inhibitors of lrrk2 kinase activity
CN102558174B (zh) * 2011-08-23 2014-03-19 天津市斯芬克司药物研发有限公司 一种全新吡唑并[4,3-c]吡啶化合物的发明及其合成方法
PT2760453T (pt) * 2011-09-30 2016-08-02 Ipsen Pharma Sas Inibidores macrocíclicos da cinase lrrk2
GB201204985D0 (en) 2012-03-21 2012-05-02 Genentech Inc Compounds
WO2013182612A1 (en) 2012-06-07 2013-12-12 Bayer Pharma Aktiengesellschaft Glucose transport inhibitors
EA025186B1 (ru) 2012-06-29 2016-11-30 Пфайзер Инк. НОВЫЕ 4-(ЗАМЕЩЕННЫЙ АМИНО)-7Н-ПИРРОЛО[2,3-d]ПИРИМИДИНЫ В КАЧЕСТВЕ ИНГИБИТОРОВ LRRK2
WO2014026330A1 (en) * 2012-08-15 2014-02-20 Merck Sharp & Dohme Corp. 3-AMINOCYCLOALKYL COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
WO2014060113A1 (en) 2012-10-19 2014-04-24 Origenis Gmbh Novel kinase inhibitors
CN104812755B (zh) * 2012-10-31 2017-08-08 拉夸里亚创药株式会社 作为ttx‑s阻断剂的吡唑并吡啶衍生物
CA2889572C (en) * 2012-11-08 2019-03-05 Pfizer Inc. Heteroaromatic compounds as dopamine d1 ligands
US9045477B2 (en) * 2013-03-15 2015-06-02 Epizyme, Inc. Substituted 6,5-fused bicyclic heteroaryl compounds
US20160024071A1 (en) * 2013-03-15 2016-01-28 Elan Pharmaceuticals, Llc Inhibitors of lrrk2 kinase activity
TW201533043A (zh) * 2013-04-18 2015-09-01 Lundbeck & Co As H 作爲ｌｒｒｋ２抑制劑的芳基吡咯并吡啶衍生化合物
AR096654A1 (es) 2013-06-20 2016-01-27 Ab Science Derivados de benzimidazol como inhibidores selectivos de proteína quinasa
WO2015026683A1 (en) * 2013-08-22 2015-02-26 Merck Sharp & Dohme Corp. Compounds inhibiting leucine-rich repeat kinase enzyme activity
EP3083618B1 (en) 2013-12-17 2018-02-21 Pfizer Inc Novel 3,4-disubstituted-1h-pyrrolo[2,3-b]pyridines and 4,5-disubstituted-7h-pyrrolo[2,3-c]pyridazines as lrrk2 inhibitors
WO2015162518A1 (en) 2014-04-25 2015-10-29 Pfizer Inc. Heteroaromatic compounds and their use as dopamine d1 ligands
PE20161475A1 (es) * 2014-05-14 2017-01-08 Pfizer Pirazolopiridinas y pirazolopirimidinas
US10954240B2 (en) 2014-09-03 2021-03-23 Merck Sharp & Dohme Corp. Compounds inhibiting leucine-rich repeat kinase enzyme activity
RU2722149C1 (ru) 2015-09-14 2020-05-27 Пфайзер Инк. Новые производные имидазо[4,5-c] хинолинов и имидазо[4,5-c][1,5] нафтиридинов в качестве ингибиторов LRRK2
WO2017215600A1 (en) 2016-06-15 2017-12-21 Suzhou Yabao Pharmaceutical R&D Co., Ltd. Substituted tricyclic herteocyclic compounds and use thereof
SG11201908234WA (en) 2017-02-24 2019-10-30 Daegu Gyeongbuk Medical Innovation Found Pharmaceutical composition comprising compound capable of penetrating blood-brain barrier as effective ingredient for preventing or treating brain cancer
EP3737680A1 (en) 2018-01-08 2020-11-18 F. Hoffmann-La Roche AG Octahydropyrido[1,2-alpha]pyrazines as magl inhibitors
KR101990738B1 (ko) * 2018-07-24 2019-06-19 재단법인 대구경북첨단의료산업진흥재단 혈액 뇌관문을 통과할 수 있는 화합물을 유효성분으로 함유하는 뇌암의 예방 또는 치료용 약학적 조성물
CN114072405A (zh) 2019-07-03 2022-02-18 豪夫迈·罗氏有限公司 杂环单酰基甘油脂肪酶(magl)抑制剂
KR20220034104A (ko) 2019-07-09 2022-03-17 에프. 호프만-라 로슈 아게 신규 헤테로고리 화합물
EP4069212A4 (en) * 2019-12-04 2024-03-06 Arcus Biosciences, Inc. INHIBITORS OF HIF-2ALPHA
UA130412C2 (uk) 2020-06-22 2026-02-11 Ф. Хоффманн-Ля Рош Аг Похідні сульфону
PE20231372A1 (es) 2020-09-03 2023-09-07 Hoffmann La Roche Compuestos heterociclicos
TWI846353B (zh) * 2022-02-25 2024-06-21 大陸商蘇州亞寶藥物研發有限公司 取代的稠環化合物及其藥物組合物、製備方法和用途

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3835144A (en) * 1972-06-16 1974-09-10 Squibb & Sons Inc Amino derivatives of (4,3-c pyrazolopyridine cabroxylic acids and esters
NZ207394A (en) 1983-03-08 1987-03-06 Commw Serum Lab Commission Detecting or determining sequence of amino acids
US5478830A (en) * 1992-05-29 1995-12-26 The Du Pont Merck Pharmaceutical Company Fused-ring heterocycles for the treatment of atherosclerosis
US5300478A (en) * 1993-01-28 1994-04-05 Zeneca Limited Substituted fused pyrazolo compounds
CN1656079A (zh) * 2002-05-31 2005-08-17 卫材株式会社 吡唑化合物和含有该化合物的药物组合物
US7186716B2 (en) * 2002-08-12 2007-03-06 Sugen, Inc. 3-Pyrrol-pyridopyrazoles and 3-pyrrolyl-indazoles as novel kinase inhibitors
US7348338B2 (en) * 2003-07-17 2008-03-25 Plexxikon, Inc. PPAR active compounds
WO2005016875A2 (en) * 2003-08-06 2005-02-24 Sugen, Inc. Geometrically restricted 3-cyclopentylidene-1,3-dihydroindol-2-ones as potent protein kinase inhibitors
WO2005121094A1 (en) * 2004-06-09 2005-12-22 Pfizer Limited Piperazine and piperidine derivatives as anti-hiv-agents
EP1772454A4 (en) * 2004-07-23 2009-02-25 Mitsubishi Tanabe Pharma Corp NITROGENIC CONDENSED BICYCLIC COMPOUND
PE20061119A1 (es) * 2005-01-19 2006-11-27 Aventis Pharma Sa PIRAZOLO PIRIDINAS SUSTITUIDAS COMO INHIBIDORES DE CINASAS FAK, KDR Y Tie
JP2009525046A (ja) * 2006-01-31 2009-07-09 エラン ファーマシューティカルズ，インコーポレイテッド アルファ−シヌクレインキナーゼ
US20100273776A1 (en) * 2006-03-29 2010-10-28 FOLDRx PHARMACEUTICALS, INC Inhibition of alpha-synuclein toxicity
PE20110854A1 (es) * 2008-09-26 2011-12-23 Boehringer Ingelheim Int DERIVADOS DE 1-FENIL-1H-PIRAZOLO[3,4-c]PIRIDINA-4-CARBONILAMINA COMO ANTAGONISTAS DE LOS RECEPTORES CCR1
GB201015949D0 (en) * 2010-09-22 2010-11-03 Medical Res Council Technology Compounds

Also Published As

Publication number Publication date
AU2010224693A1 (en) 2011-09-15
CN102428084A (zh) 2012-04-25
RU2011142182A (ru) 2013-04-27
US20100317646A1 (en) 2010-12-16
US20170320870A1 (en) 2017-11-09
EP2408772A1 (en) 2012-01-25
PE20120506A1 (es) 2012-05-14
KR20110128925A (ko) 2011-11-30
AU2010224693B2 (en) 2016-07-28
EP2408772B1 (en) 2015-07-01
IL215147A0 (en) 2011-12-29
CN102428084B (zh) 2016-05-18
KR101700229B1 (ko) 2017-01-26
CA2754605A1 (en) 2010-09-23
WO2010106333A1 (en) 2010-09-23
MX2011009807A (es) 2011-09-29
CL2011002267A1 (es) 2012-05-11
JP2012520861A (ja) 2012-09-10
JP5732036B2 (ja) 2015-06-10

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