PL2308877T3 - Pochodne imidazopirydyn-2-onu - Google Patents

Pochodne imidazopirydyn-2-onu

Info

Publication number
PL2308877T3
PL2308877T3 PL09804973T PL09804973T PL2308877T3 PL 2308877 T3 PL2308877 T3 PL 2308877T3 PL 09804973 T PL09804973 T PL 09804973T PL 09804973 T PL09804973 T PL 09804973T PL 2308877 T3 PL2308877 T3 PL 2308877T3
Authority
PL
Poland
Prior art keywords
imidazopyridin
derivatives
Prior art date
Application number
PL09804973T
Other languages
English (en)
Inventor
Masami Ohtsuka
Noriyasu Haginoya
Masanori Ichikawa
Hironori Matsunaga
Hironao Saito
Yoshihiro Shibata
Tomoyuki Tsunemi
Original Assignee
Daiichi Sankyo Co Ltd
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 Daiichi Sankyo Co Ltd filed Critical Daiichi Sankyo Co Ltd
Publication of PL2308877T3 publication Critical patent/PL2308877T3/pl

Links

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
    • A61K31/4353—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
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines 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
    • A61K31/435—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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • 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

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
PL09804973T 2008-08-05 2009-08-04 Pochodne imidazopirydyn-2-onu PL2308877T3 (pl)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2008201670 2008-08-05
JP2009078540 2009-03-27
PCT/JP2009/063807 WO2010016490A1 (ja) 2008-08-05 2009-08-04 イミダゾピリジン－２－オン誘導体
EP09804973.7A EP2308877B1 (en) 2008-08-05 2009-08-04 Imidazopyridin-2-one derivatives

Publications (1)

Publication Number Publication Date
PL2308877T3 true PL2308877T3 (pl) 2014-07-31

Family

ID=41663708

Family Applications (1)

Application Number Title Priority Date Filing Date
PL09804973T PL2308877T3 (pl) 2008-08-05 2009-08-04 Pochodne imidazopirydyn-2-onu

Country Status (21)

Country Link
US (2) US8436012B2 (pl)
EP (1) EP2308877B1 (pl)
JP (1) JP5630867B2 (pl)
KR (1) KR20110039307A (pl)
CN (1) CN102171210B (pl)
AU (1) AU2009278442B2 (pl)
BR (1) BRPI0917540A2 (pl)
CA (1) CA2732950C (pl)
CO (1) CO6300866A2 (pl)
DK (1) DK2308877T3 (pl)
ES (1) ES2459047T3 (pl)
IL (1) IL211042A (pl)
MX (1) MX2011001019A (pl)
MY (1) MY153606A (pl)
NZ (1) NZ590688A (pl)
PL (1) PL2308877T3 (pl)
PT (1) PT2308877E (pl)
RU (1) RU2478636C2 (pl)
TW (1) TWI436998B (pl)
WO (1) WO2010016490A1 (pl)
ZA (1) ZA201100799B (pl)

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102264743B (zh) 2008-11-25 2015-02-11 罗彻斯特大学 Mlk抑制剂及其使用方法
WO2011021678A1 (ja) * 2009-08-21 2011-02-24 武田薬品工業株式会社 縮合複素環化合物
NZ603644A (en) 2010-05-24 2014-10-31 Univ Rochester Bicyclic heteroaryl kinase inhibitors and methods of use
WO2012003576A1 (en) * 2010-07-06 2012-01-12 Université de Montréal Imidazopyridine, imidazopyrimidine and imidazopyrazine derivatives as melanocortin-4 receptor modulators
CA2825098C (en) 2011-01-27 2020-03-10 Universite De Montreal Pyrazolopyridine and pyrazolopyrimidine derivatives as melanocortin-4 receptor modulators
KR101274986B1 (ko) * 2011-07-27 2013-06-17 한국과학기술원 이미다조피리딘 유도체, 이를 포함하는 ＰＩ3Ｋ 및/또는 ｍＴＯＲ 저해제용 약학 조성물 및 ＰＩ3Ｋ 및/또는 ｍＴＯＲ과 연관된 질환 치료용 약학 조성물
CN102702196B (zh) * 2012-06-13 2015-01-14 南京药石药物研发有限公司 3-甲基-7-氮杂吲哚的合成方法
CA2884766A1 (en) * 2012-10-16 2014-04-24 Daniel Jon Burdick Serine/threonine kinase inhibitors
EP2925319B1 (en) 2012-11-30 2019-01-09 University Of Rochester Mixed lineage kinase inhibitors for hiv/aids therapies
CA2902858A1 (en) * 2013-02-28 2014-09-04 Signal Pharmaceuticals, Llc Treatment of cancer with tor kinase inhibitors
CA2938626A1 (en) 2013-07-26 2015-01-29 John Rothman Compositions to improve the therapeutic benefit of bisantrene
JP6522502B2 (ja) 2013-07-29 2019-05-29 協和発酵キリン株式会社 Ｗｎｔシグナル阻害剤
PT3180329T (pt) 2014-08-15 2020-06-08 Janssen Pharmaceuticals Inc Triazóis como inibidores do recetor nr2b
HUE049278T2 (hu) 2014-08-15 2020-09-28 Janssen Pharmaceuticals Inc Pirazolok
LT3319963T (lt) 2015-07-09 2020-03-25 Janssen Pharmaceutica Nv Pakeistieji 4-azaindolai ir jų, kaip glun2b receptoriaus moduliatorių, panaudojimas
CA3014314A1 (en) 2016-02-10 2017-08-17 Janssen Pharmaceutica Nv Substituted 1,2,3-triazoles as nr2b-selective nmda modulators
EA039529B1 (ru) 2016-04-28 2022-02-07 Такеда Фармасьютикал Компани Лимитед Конденсированные гетероциклические соединения
CN106187899B (zh) * 2016-06-28 2019-07-16 绍兴文理学院 一种氟代氮杂芳烃的合成方法
TW201819376A (zh) 2016-10-06 2018-06-01 比利時商健生藥品公司 經取代之１Ｈ－咪唑並［４，５－ｂ］吡啶－２（３Ｈ）－酮及其作為ＧＬＵＮ２Ｂ受體調節劑之用途
US11447503B2 (en) 2019-06-14 2022-09-20 Janssen Pharmaceutica Nv Pyridine carbamates and their use as GLUN2B receptor modulators
CN107118084B (zh) * 2017-06-27 2021-06-08 江苏合泰新材料科技有限公司 一种两步法合成1,3-双取代基-2-丙醇的方法
CN107550905B (zh) * 2017-09-11 2020-07-17 浙江永宁药业股份有限公司 多取代吡咯并吡啶类化合物的药物用途及其制备方法
WO2019193516A2 (en) 2018-04-04 2019-10-10 Janssen Pharmaceutica Nv Substituted pyridine and pyrimidines and their use as glun2b receptor modulators
WO2019236884A1 (en) 2018-06-07 2019-12-12 Disarm Therapeutics, Inc. Inhibitors of sarm1
TWI837231B (zh) 2018-11-29 2024-04-01 日商第一三共股份有限公司 含有ｅｚｈ１／２雙重抑制劑之醫藥組合及其用途
CA3123215C (en) 2018-12-19 2024-04-02 Disarm Therapeutics, Inc. Inhibitors of sarm1 in combination with neuroprotective agents
PH12021552839A1 (en) 2019-06-14 2022-10-03 Janssen Pharmaceutica Nv Substituted pyrazolo-pyridine amides and their use as glun2b receptor modulators
US11459336B2 (en) 2019-06-14 2022-10-04 Janssen Pharmaceutica Nv Pyrazine carbamates and their use as GluN2B receptor modulators
KR20220024403A (ko) 2019-06-14 2022-03-03 얀센 파마슈티카 엔.브이. 치환된 피라졸로-피라진 및 이들의 glun2b 수용체 조절제로서의 용도
BR112021025141A2 (pt) 2019-06-14 2022-01-25 Janssen Pharmaceutica Nv Pirazolo-piridinas heteroaromáticas substituídas e seu uso como moduladores do receptor glun2b
CN113993583A (zh) 2019-06-14 2022-01-28 詹森药业有限公司 取代的吡唑并[4,3-b]吡啶及其作为GLUN2B受体调节剂的用途
EP3983075A1 (en) 2019-06-14 2022-04-20 Janssen Pharmaceutica NV Substituted pyrazolo-pyridine amides and their use as glun2b receptor modulators
WO2022166920A1 (zh) * 2021-02-08 2022-08-11 杭州中美华东制药有限公司 一种吡咯并哒嗪类化合物及其制备方法和用途
EP4074712A1 (en) 2021-04-13 2022-10-19 Siegfried AG Process for the synthesis of 1,3-dihydro-imidazo[4,5-b]pyridin-2-one and/or derivatives thereof
EP4602043A1 (en) 2022-10-14 2025-08-20 Genesis Therapeutics, Inc. 4h-pyrido[1,2-a]pyrimidin-4-one derivatives for treating cancer

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4294837A (en) 1980-03-28 1981-10-13 Sterling Drug Inc. 1,3-Dihydro-6-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones and -imidazo[4,5-b]pyridine-2-thiones and their cardiotonic use
US4532337A (en) 1984-02-28 1985-07-30 Basf Aktiengesellschaft Preparation of 3-formyl-5,6-dihydro-2H-pyran
JPH0678327B2 (ja) 1989-07-20 1994-10-05 ファイザー製薬株式会社 ４，５，６，７，―四置換ベンゾオキサゾロン類
IN188411B (pl) 1997-03-27 2002-09-21 Yuhan Corp
WO1999057103A1 (en) * 1998-04-30 1999-11-11 Nippon Chemiphar Co., Ltd. Condensed imidazole derivative and therapeutic agent for liver disease
WO2001019831A1 (en) 1999-09-10 2001-03-22 Novo Nordisk A/S MODULATORS OF PROTEIN TYROSINE PHOSPHATASES (PTPases)
US7511144B2 (en) 2001-09-07 2009-03-31 Kaken Pharmaceutical Co., Ltd. Reverse hydroxamic acid derivatives
WO2003028724A1 (en) 2001-10-04 2003-04-10 Smithkline Beecham Corporation Chk1 kinase inhibitors
JP2003221386A (ja) 2001-11-26 2003-08-05 Takeda Chem Ind Ltd 二環性誘導体、その製造法およびその用途
DE10228103A1 (de) 2002-06-24 2004-01-15 Bayer Cropscience Ag Fungizide Wirkstoffkombinationen
AU2003294249A1 (en) 2002-11-08 2004-06-03 Trimeris, Inc. Hetero-substituted benzimidazole compounds and antiviral uses thereof
BR0316991A (pt) * 2002-12-04 2005-10-25 Eisai Co Ltd Compostos de anel de 1,3-diidro-imidazol fundido
US7612086B2 (en) 2003-05-16 2009-11-03 Eisai R & D Management Co. Ltd. JNK inhibitors
US7563748B2 (en) 2003-06-23 2009-07-21 Cognis Ip Management Gmbh Alcohol alkoxylate carriers for pesticide active ingredients
AU2004268950A1 (en) * 2003-08-21 2005-03-10 Osi Pharmaceuticals, Inc. N3-substituted imidazopyridine-derivatives as c-kit inhibitors
ES2241496B1 (es) 2004-04-15 2006-12-01 Almirall Prodesfarma, S.A. Nuevos derivados de piridina.
RU2346996C2 (ru) 2004-06-29 2009-02-20 ЮРОПИЭН НИКЕЛЬ ПиЭлСи Усовершенствованное выщелачивание основных металлов
US7361763B2 (en) 2004-07-27 2008-04-22 Sgx Pharmaceuticals, Inc. Pyrrolo-pyridine kinase modulators
GB0420719D0 (en) 2004-09-17 2004-10-20 Addex Pharmaceuticals Sa Novel allosteric modulators
US7745470B2 (en) 2005-03-10 2010-06-29 Bristol-Myers Squibb Company Isophthalates as beta-secretase inhibitors
US7994325B2 (en) * 2005-03-14 2011-08-09 Merck Sharp & Dohme Corp. CGRP receptor antagonists
WO2006126081A2 (en) 2005-05-24 2006-11-30 Pharmacia & Upjohn Company Llc Pyridino [2 , 3-b] pyrazinones as pde-5 inhibitors
KR101280096B1 (ko) 2005-06-29 2013-06-28 컴퓨메딕스 리미티드 전도성 브리지를 포함하는 센서 어셈블리
GB0513840D0 (en) 2005-07-07 2005-08-10 Medivir Ab Cysteine protease inhibitors
TWI411607B (zh) 2005-11-14 2013-10-11 Vitae Pharmaceuticals Inc 天門冬胺酸蛋白酶抑制劑
US8097617B2 (en) 2006-03-31 2012-01-17 Novartis Ag Organic compounds
EP2029593A1 (en) 2006-05-22 2009-03-04 AstraZeneca AB Indole derivatives
TW200801513A (en) 2006-06-29 2008-01-01 Fermiscan Australia Pty Ltd Improved process
WO2008011557A2 (en) 2006-07-20 2008-01-24 Borchardt Allen J Heteroaryl inhibitors of rho kinase
AU2007287430B2 (en) 2006-08-23 2011-07-21 Kudos Pharmaceuticals Limited 2-methylmorpholine pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mTOR inhibitors
JP4388997B2 (ja) 2006-09-05 2009-12-24 協和発酵キリン株式会社 イミダゾール誘導体
NZ576278A (en) * 2006-10-19 2011-12-22 Signal Pharm Llc Heteroaryl compounds, compositions thereof, and their use as protein kinase inhibitors
MX2009004019A (es) * 2006-10-19 2009-06-19 Signal Pharm Llc Compuestos heteroarilo, composiciones de los mismos, y uso de los mismos como inhibidores de proteina cinasa.
TW200901998A (en) 2007-03-06 2009-01-16 Astrazeneca Ab Novel 2-heteroaryl substituted benzothiophenes and benzofuranes
CN101815712A (zh) 2007-08-01 2010-08-25 辉瑞有限公司 吡唑化合物及其作为raf抑制剂的用途
EP2311842A3 (en) 2008-06-24 2011-07-13 Takeda Pharmaceutical Company Limited PI3K/M TOR inhibitors
WO2010000020A1 (en) 2008-06-30 2010-01-07 Cathrx Ltd A catheter
CA2733554A1 (en) 2008-08-18 2010-02-25 Yale University Mif modulators
CN102264743B (zh) 2008-11-25 2015-02-11 罗彻斯特大学 Mlk抑制剂及其使用方法
WO2011000020A1 (en) 2009-06-12 2011-01-06 Sbc Research Pty Ltd Enhanced method of detection
WO2011096490A1 (ja) * 2010-02-04 2011-08-11 第一三共株式会社 イミダゾピリジン－２－オン誘導体

Also Published As

Publication number Publication date
TWI436998B (zh) 2014-05-11
US8436012B2 (en) 2013-05-07
IL211042A0 (en) 2011-04-28
RU2011108453A (ru) 2012-09-10
JP5630867B2 (ja) 2014-11-26
CA2732950A1 (en) 2010-02-11
US20110082138A1 (en) 2011-04-07
JPWO2010016490A1 (ja) 2012-01-26
CN102171210A (zh) 2011-08-31
KR20110039307A (ko) 2011-04-15
MY153606A (en) 2015-02-27
CO6300866A2 (es) 2011-07-21
EP2308877B1 (en) 2014-01-22
EP2308877A4 (en) 2012-03-14
TW201011021A (en) 2010-03-16
PT2308877E (pt) 2014-05-02
EP2308877A1 (en) 2011-04-13
CA2732950C (en) 2013-10-01
AU2009278442B2 (en) 2013-09-26
IL211042A (en) 2014-12-31
ZA201100799B (en) 2011-10-26
CN102171210B (zh) 2014-04-23
HK1155444A1 (en) 2012-05-18
ES2459047T3 (es) 2014-05-07
US20130338156A1 (en) 2013-12-19
AU2009278442A1 (en) 2010-02-11
NZ590688A (en) 2012-09-28
RU2478636C2 (ru) 2013-04-10
DK2308877T3 (da) 2014-04-22
US8785438B2 (en) 2014-07-22
WO2010016490A1 (ja) 2010-02-11
MX2011001019A (es) 2011-03-25
BRPI0917540A2 (pt) 2015-11-17

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