CN102459233B - 二取代的酞嗪hedgehog途径拮抗剂 - Google Patents

二取代的酞嗪hedgehog途径拮抗剂 Download PDF

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Publication number
CN102459233B
CN102459233B CN201080027189.3A CN201080027189A CN102459233B CN 102459233 B CN102459233 B CN 102459233B CN 201080027189 A CN201080027189 A CN 201080027189A CN 102459233 B CN102459233 B CN 102459233B
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cancer
methyl
compound
acceptable salt
pharmaceutically acceptable
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Chinese (zh)
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CN102459233A (zh
Inventor
P·A·希普斯金德
B·K·帕特尔
T·威尔森(尼高桑)
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Eli Lilly and Co
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Eli Lilly and Co
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    • 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
    • C07D401/14—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 three or more hetero 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring 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
    • A61K31/495—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
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CN201080027189.3A 2009-06-19 2010-06-15 二取代的酞嗪hedgehog途径拮抗剂 Active CN102459233B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US21862809P 2009-06-19 2009-06-19
US61/218,628 2009-06-19
PCT/US2010/038568 WO2010147917A1 (en) 2009-06-19 2010-06-15 Disubstituted phthalazine hedgehog pathway antagonists

Publications (2)

Publication Number Publication Date
CN102459233A CN102459233A (zh) 2012-05-16
CN102459233B true CN102459233B (zh) 2014-07-02

Family

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CN201080027189.3A Active CN102459233B (zh) 2009-06-19 2010-06-15 二取代的酞嗪hedgehog途径拮抗剂

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US (2) US8273742B2 (enExample)
EP (1) EP2443104B1 (enExample)
JP (1) JP5596139B2 (enExample)
KR (1) KR101389165B1 (enExample)
CN (1) CN102459233B (enExample)
AR (1) AR077014A1 (enExample)
AU (1) AU2010260244B2 (enExample)
BR (1) BRPI1011601A2 (enExample)
CA (1) CA2764542C (enExample)
CL (1) CL2011003147A1 (enExample)
CO (1) CO6480932A2 (enExample)
CR (1) CR20110658A (enExample)
DK (1) DK2443104T3 (enExample)
DO (1) DOP2011000386A (enExample)
EA (1) EA019059B1 (enExample)
EC (1) ECSP11011541A (enExample)
ES (1) ES2409054T3 (enExample)
HN (1) HN2011003139A (enExample)
HR (1) HRP20130408T1 (enExample)
IL (1) IL216599A (enExample)
JO (1) JO2931B1 (enExample)
MA (1) MA33363B1 (enExample)
MX (1) MX2011014029A (enExample)
MY (1) MY156667A (enExample)
NZ (1) NZ596882A (enExample)
PE (1) PE20121050A1 (enExample)
PL (1) PL2443104T3 (enExample)
PT (1) PT2443104E (enExample)
SG (1) SG177289A1 (enExample)
SI (1) SI2443104T1 (enExample)
TN (1) TN2011000627A1 (enExample)
TW (1) TWI385165B (enExample)
UA (1) UA106755C2 (enExample)
WO (1) WO2010147917A1 (enExample)
ZA (1) ZA201108587B (enExample)

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JP5442717B2 (ja) * 2008-04-29 2014-03-12 イーライ リリー アンド カンパニー 二置換フタラジンヘッジホッグ経路アンタゴニスト
CA2742539C (en) * 2008-11-03 2014-05-06 Eli Lilly And Company Disubstituted phthalazine hedgehog pathway antagonists
EP2358703B1 (en) * 2008-11-17 2013-12-25 Eli Lilly and Company Tetrasubstituted pyridazines hedgehog pathway antagonists
DK2358698T3 (da) 2008-11-17 2012-10-08 Lilly Co Eli Tetrasubstitueret pyridazin som hedgehog-pathway antagonister
AR077014A1 (es) 2009-06-19 2011-07-27 Lilly Co Eli Compuesto derivado de ftalazina 1,4-disustituida, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para el tratamiento de cancer
EP2688565A1 (en) 2011-03-23 2014-01-29 Semorex Technologies Ltd. Treatment of proliferative disorders with a chemiluminescent agent
GB201309508D0 (en) * 2013-05-28 2013-07-10 Redx Pharma Ltd Compounds
GB201311953D0 (en) * 2013-07-03 2013-08-14 Redx Pharma Ltd Compounds
US9814703B2 (en) 2013-11-14 2017-11-14 The Board Of Trustees Of The Leland Stanford Junior University Methods for treating cancer by activation of BMP signaling
CN105017140B (zh) * 2014-04-28 2017-12-29 复旦大学 邻氨基苯甲酰胺化合物及其制备方法和用途
GB2528298A (en) * 2014-07-16 2016-01-20 Redx Pharma Plc Compounds
CN105985321B (zh) * 2015-02-11 2018-10-26 复旦大学 吡唑酞嗪化合物及其制备方法和用途
CN105985320B (zh) * 2015-02-11 2018-10-26 复旦大学 苄基酞嗪化合物及其制备方法和用途
CN105985319B (zh) * 2015-02-11 2019-02-26 复旦大学 芳基酞嗪化合物及其制备方法和用途
JP6796638B2 (ja) 2015-06-04 2020-12-09 ペレファーム, インク.Pellepharm, Inc. ヘッジホッグ阻害性化合物の送達のための局所的製剤及びその使用
CA2987067A1 (en) * 2015-06-05 2016-12-08 Dana-Farber Cancer Institute, Inc. Compounds and methods for treating cancer
WO2017157825A1 (en) 2016-03-15 2017-09-21 F. Hoffmann-La Roche Ag Combinations of lsd1 inhibitors for use in the treatment of solid tumors
CN106279114B (zh) * 2016-08-04 2019-01-29 东南大学 一种Taladegib的合成方法
US10548908B2 (en) * 2016-09-15 2020-02-04 Nostopharma, LLC Compositions and methods for preventing and treating heterotopic ossification and pathologic calcification
CN106831718B (zh) * 2016-12-30 2019-05-07 上海科技大学 平滑受体配体及其应用
EP3624798A1 (en) 2017-05-18 2020-03-25 Institut National de la Sante et de la Recherche Medicale (INSERM) Methods and pharmaceutical compositions for the treatment of mast cell diseases
CA3184767A1 (en) 2020-06-26 2021-12-30 Raqualia Pharma Inc. Method for selecting cancer patients for whom combination therapy with retinoid and cancer therapeutic agent is effective, and combination medicament with retinoid and cancer therapeutic agent
JP2023546536A (ja) * 2020-10-13 2023-11-02 エンデバー バイオメディシンズ， インコーポレイテッド 線維症を処置する方法
WO2025188802A1 (en) 2024-03-05 2025-09-12 Endeavor Biomedicines, Inc. Methods of improving lung function
WO2025189041A1 (en) * 2024-03-07 2025-09-12 Endeavor Biomedicines, Inc. Methods of treating fibrosis
WO2025242197A1 (zh) * 2024-05-24 2025-11-27 成都思倍博医药科技有限公司 氘代的Hedgehog通路SMO受体抑制剂

Citations (3)

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CN1638765A (zh) * 2001-07-27 2005-07-13 柯里斯公司 Hedgehog信号转导途径介质、其相关组合物以及应用
WO2009002469A1 (en) * 2007-06-25 2008-12-31 Amgen Inc. Phthalazine compounds, compositions and methods of use
WO2009074300A2 (en) * 2007-12-13 2009-06-18 Siena Biotech S.P.A. Hedgehog pathway antagonists and therapeutic applications thereof

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AU768130B2 (en) 1998-04-09 2003-12-04 Johns Hopkins University School Of Medicine, The Use of steroidal alkaloid derivatives as inhibitors of hedgehog signaling pathways
ATE283700T1 (de) 1999-06-08 2004-12-15 Lorantis Ltd Therapeutische verwendung eines inhibitors des hedgehog signalübertragungsweges
US7655674B2 (en) * 2002-04-22 2010-02-02 The Johns Hopkins University Modulators of hedgehog signaling pathways, compositions and uses related thereto
AU2003265853A1 (en) 2002-08-29 2004-03-19 Curis, Inc. Hedgehog antagonists, methods and uses related thereto
WO2005033288A2 (en) 2003-09-29 2005-04-14 The Johns Hopkins University Hedgehog pathway antagonists
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WO2006004589A2 (en) 2004-05-08 2006-01-12 Neurogen Corporation 3-aryl-5,6-disubstituted pyridazines
AU2005282722C1 (en) 2004-09-02 2011-08-18 Curis, Inc. Pyridyl inhibitors of hedgehog signalling
EP1900731A1 (de) * 2006-09-07 2008-03-19 Bayer Schering Pharma Aktiengesellschaft N-(1-Phthalazin-1-yl-piperidin-4-yl)-amide als EP2-Rezeptor Modulatoren
KR101473504B1 (ko) * 2007-03-15 2014-12-16 노파르티스 아게 유기 화합물 및 그의 용도
EP2188283B1 (en) 2007-09-07 2012-08-15 Amgen Inc. Annelated pyridazines for the treatment of tumors driven by inappropriate hedgehog signalling
JP5442717B2 (ja) 2008-04-29 2014-03-12 イーライ リリー アンド カンパニー 二置換フタラジンヘッジホッグ経路アンタゴニスト
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ES2433469T3 (es) * 2008-08-04 2013-12-11 Amgen Inc. Moduladores de la aurora cinasa y métodos de uso
CA2742539C (en) 2008-11-03 2014-05-06 Eli Lilly And Company Disubstituted phthalazine hedgehog pathway antagonists
DK2358698T3 (da) 2008-11-17 2012-10-08 Lilly Co Eli Tetrasubstitueret pyridazin som hedgehog-pathway antagonister
EP2358703B1 (en) 2008-11-17 2013-12-25 Eli Lilly and Company Tetrasubstituted pyridazines hedgehog pathway antagonists
AR077014A1 (es) 2009-06-19 2011-07-27 Lilly Co Eli Compuesto derivado de ftalazina 1,4-disustituida, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para el tratamiento de cancer

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
CN1638765A (zh) * 2001-07-27 2005-07-13 柯里斯公司 Hedgehog信号转导途径介质、其相关组合物以及应用
WO2009002469A1 (en) * 2007-06-25 2008-12-31 Amgen Inc. Phthalazine compounds, compositions and methods of use
WO2009074300A2 (en) * 2007-12-13 2009-06-18 Siena Biotech S.P.A. Hedgehog pathway antagonists and therapeutic applications thereof

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AU2010260244A1 (en) 2012-01-19
ECSP11011541A (es) 2012-01-31
HK1164872A1 (en) 2012-09-28
CA2764542A1 (en) 2010-12-23
ES2409054T3 (es) 2013-06-24
AR077014A1 (es) 2011-07-27
TN2011000627A1 (en) 2013-05-24
US8273742B2 (en) 2012-09-25
MY156667A (en) 2016-03-15
WO2010147917A1 (en) 2010-12-23
IL216599A (en) 2015-09-24
JP5596139B2 (ja) 2014-09-24
MX2011014029A (es) 2012-02-21
KR101389165B1 (ko) 2014-04-24
EA201270049A1 (ru) 2012-05-30
NZ596882A (en) 2013-08-30
EP2443104B1 (en) 2013-04-17
CR20110658A (es) 2012-02-20
SI2443104T1 (sl) 2013-07-31
HN2011003139A (es) 2013-07-29
TW201113268A (en) 2011-04-16
ZA201108587B (en) 2013-05-29
HRP20130408T1 (en) 2013-06-30
US20100324048A1 (en) 2010-12-23
CL2011003147A1 (es) 2012-07-20
EP2443104A1 (en) 2012-04-25
CA2764542C (en) 2013-09-10
US9000023B2 (en) 2015-04-07
JP2012530705A (ja) 2012-12-06
TWI385165B (zh) 2013-02-11
US20120316174A1 (en) 2012-12-13
CO6480932A2 (es) 2012-07-16
UA106755C2 (uk) 2014-10-10
BRPI1011601A2 (pt) 2016-03-22
AU2010260244B2 (en) 2013-09-05
MA33363B1 (fr) 2012-06-01
DK2443104T3 (da) 2013-05-06
DOP2011000386A (es) 2012-02-29
PE20121050A1 (es) 2012-08-09
SG177289A1 (en) 2012-02-28
PL2443104T3 (pl) 2013-08-30
IL216599A0 (en) 2012-03-01
PT2443104E (pt) 2013-05-07
EA019059B1 (ru) 2013-12-30
KR20120024783A (ko) 2012-03-14
CN102459233A (zh) 2012-05-16
JO2931B1 (en) 2015-09-15

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