TWI605040B - 作為ｍＧｌｕＲ２負向異位性調節劑之喹啉甲醯胺及喹啉甲腈衍生物、組合物及其用途 - Google Patents

作為ｍＧｌｕＲ２負向異位性調節劑之喹啉甲醯胺及喹啉甲腈衍生物、組合物及其用途 Download PDF

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TWI605040B
TWI605040B TW101140837A TW101140837A TWI605040B TW I605040 B TWI605040 B TW I605040B TW 101140837 A TW101140837 A TW 101140837A TW 101140837 A TW101140837 A TW 101140837A TW I605040 B TWI605040 B TW I605040B
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alkyl
group
phenyl
compound
mmol
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TW101140837A
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TW201321357A (zh
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克里斯多夫 詹姆士 邦賈德
安東尼拉 康瓦索
里昂 帕布羅 帝
芭芭拉 漢尼
提摩西 約翰 哈汀
傑西 喬瑟夫 曼尼柯斯基
彼德Ｊ 曼利
羅伯 梅斯納
孟昭洋
詹姆士Ｊ 柏金斯
麥可Ｔ 路德
徐瑜涵
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默沙東公司
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    • C07—ORGANIC CHEMISTRY
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    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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    • 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
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    • 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
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    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
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    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
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    • 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
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    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • 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
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    • C07D401/06—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 only aliphatic carbon atoms
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    • 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
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    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • 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
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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems

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  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Anesthesiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Quinoline Compounds (AREA)
TW101140837A 2011-11-03 2012-11-02 作為ｍＧｌｕＲ２負向異位性調節劑之喹啉甲醯胺及喹啉甲腈衍生物、組合物及其用途 TWI605040B (zh)

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US201161555227P 2011-11-03 2011-11-03
US201261672334P 2012-07-17 2012-07-17

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TW201321357A TW201321357A (zh) 2013-06-01
TWI605040B true TWI605040B (zh) 2017-11-11

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US (3) US9278960B2 (enExample)
EP (1) EP2775841B1 (enExample)
JP (2) JP5857136B2 (enExample)
KR (1) KR20140088887A (enExample)
CN (1) CN104010504B (enExample)
AR (1) AR088611A1 (enExample)
AU (2) AU2012332895B2 (enExample)
CA (1) CA2853923A1 (enExample)
CO (1) CO6950474A2 (enExample)
IL (1) IL232291A0 (enExample)
IN (1) IN2014CN03234A (enExample)
MX (1) MX344308B (enExample)
MY (1) MY167423A (enExample)
RU (1) RU2610262C2 (enExample)
TW (1) TWI605040B (enExample)
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Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9278960B2 (en) 2011-11-03 2016-03-08 Merck Sharp & Dohme Corp. Quinoline carboxamide and quinoline carbonitrile derivatives as mGluR2-negative allosteric modulators, compositions, and their use
JO3368B1 (ar) 2013-06-04 2019-03-13 Janssen Pharmaceutica Nv مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2
JP6377245B2 (ja) * 2014-03-24 2018-08-22 グアンドン ジョンシェン ファーマシューティカル カンパニー リミテッド Ｓｍｏ阻害剤としてのキノリン誘導体
CN107001373B (zh) 2014-08-01 2020-01-07 詹森药业有限公司 6,7-二氢吡唑并[1,5-a]吡嗪-4(5H)-酮化合物及其作为MGLUR2受体的负向别构调节剂的用途
JO3601B1 (ar) 2014-08-01 2020-07-05 Janssen Pharmaceutica Nv مركبات 6 ، 7 ثاني هيدرو بيرازولو [ 1، 5 الفا ] بيرازين – 4 (5 يد) – اون واستخدامها كمنظمات الوسترية سلبية لمستقبلات ملجور 2
JOP20150177B1 (ar) 2014-08-01 2021-08-17 Janssen Pharmaceutica Nv مركبات 6 ، 7 ثاني هيدرو بيرازولو [ 1، 5 الفا ] بيرازين – 4 (5 يد) – اون واستخدامها كمنظمات الوسترية سلبية لمستقبلات ملجور 2
JOP20150179B1 (ar) 2014-08-01 2021-08-17 Janssen Pharmaceutica Nv مركبات 6 ، 7 ثاني هيدرو بيرازولو [ 1، 5 الفا ] بيرازين – 4 (5 يد) – اون واستخدامها كمنظمات الوسترية سلبية لمستقبلات ملجور 2
RU2708391C2 (ru) 2014-08-01 2019-12-06 Янссен Фармацевтика Нв 6,7-дигидропиразоло[1,5-а]пиразин-4(5h)-оновые соединения и их применение в качестве отрицательных аллостерических модуляторов рецепторов mglur2
WO2016029454A1 (en) * 2014-08-29 2016-03-03 Merck Sharp & Dohme Corp. TETRAHYDRONAPHTHYRIDINE DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE
EP3000814A1 (en) 2014-09-26 2016-03-30 Domain Therapeutics Substituted pyrazoloquinazolinones and pyrroloquinazolinones as allosteric modulators of group II metabotropic glutamate receptors
AU2015357169B2 (en) 2014-12-03 2021-03-04 Janssen Pharmaceutica Nv Radiolabelled mGluR2 PET ligands
EP3227295B1 (en) 2014-12-03 2019-02-20 Janssen Pharmaceutica NV 6,7-dihydropyrazolo[1,5- ]pyrazin-4(5h)-one compounds and their use as negative allosteric modulators of mglu2 receptors
US10538491B2 (en) 2015-03-16 2020-01-21 Vanderbilt University 4,5-substituted picolinamide and picolinonitrile metabotropic glutamate receptor 2 negative allosteric modulators
CR20180109A (es) 2015-07-20 2018-05-03 Genzyme Corp Inhibidores de receptor del factor estimulador de colonias 1 (csf-1r)
CN108430986B (zh) 2015-10-26 2021-08-31 拜耳作物科学股份公司 作为有害生物控制剂的稠合双环杂环衍生物
RS60981B1 (sr) 2015-12-18 2020-11-30 Janssen Pharmaceutica Nv Radiooznačeni mglur2/3 pet ligandi
EA037941B1 (ru) 2015-12-18 2021-06-09 Янссен Фармацевтика Нв ЛИГАНДЫ mGluR2/3 ДЛЯ PET, МЕЧЕННЫЕ РАДИОАКТИВНЫМИ ИЗОТОПАМИ
SI3519416T1 (sl) * 2016-09-27 2021-08-31 Merck Sharp & Dohme Corp. Derivati kromana, izokromana in dihidroizobenzofurana kot mGluR2-negativni alosterični modulatorji, sestavki in njihova uporaba
MY201041A (en) 2017-11-24 2024-01-31 Sumitomo Pharma Co Ltd Substituted pyrazolo[1,5-a]pyrazines as negative allosteric modulators of group ii metabotropic glutamate receptor
CN108689957B (zh) * 2018-07-23 2020-07-03 南京药石科技股份有限公司 一种2r/2s-三氟甲基吗啉及其盐酸盐的制备方法和应用
EP3877356A4 (en) * 2018-11-09 2022-06-22 Vivace Therapeutics, Inc. BICYCLIC LINKS
AU2020257207B2 (en) 2019-04-16 2026-06-04 Vivace Therapeutics, Inc. Bicyclic compounds
EP3976027B1 (en) 2019-05-30 2025-11-05 Merck Sharp & Dohme LLC Quinoline derivatives as factor xi activation inhibitors
MX2021015872A (es) 2019-07-01 2022-02-03 UCB Biopharma SRL Un derivado de tetrahidroisoquinolina sustituido como modulador alosterico positivo de d1.
PH12021552825A1 (en) 2019-07-01 2022-10-03 UCB Biopharma SRL A substituted tetrahydroisoquinoline derivative as a d1 positive allosteric modulator
CN110256342B (zh) * 2019-07-16 2022-06-07 河南省科学院化学研究所有限公司 一种2-氰基喹啉衍生物的合成方法
ES3004257T3 (en) 2020-12-18 2025-03-12 UCB Biopharma SRL Prodrugs of 2-(3,5-dichloro-1-methyl-indazol-4-yl)-1-[(1s,3r)-3-(hydroxymethyl)-5-(1-hydroxy-1-methyl-ethyl)-1-methyl-3,4-dihydro-1h-isoquinolin-2-yl]ethanone
SI4263517T1 (sl) 2020-12-18 2025-01-31 UCB Biopharma SRL Substituiran tetrahidroizokinolinski derivat kot pozitivni alosterični modulator d1
US11530216B2 (en) 2020-12-23 2022-12-20 Genzyme Corporation Deuterated colony stimulating factor-1 receptor (CSF-1R) inhibitors
WO2024112853A1 (en) * 2022-11-24 2024-05-30 Exelixis, Inc. Compounds that inhibit pkmyt1
WO2025101691A1 (en) * 2023-11-08 2025-05-15 Exelixis, Inc. Methods for treating cancer using compounds that inhibit pkmyt1
CN119613413B (zh) * 2024-12-26 2026-02-06 上海皓元医药股份有限公司 一种非唑奈坦的制备方法

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0551831A1 (de) * 1992-01-15 1993-07-21 Hoechst Schering AgrEvo GmbH Verfahren zur Herstellung substituierter 2-Cyanopyridine
US5552437A (en) 1994-10-27 1996-09-03 Merck Frosst Canada, Inc. Bisarylcarbinol derivatives as inhibitors of leukotriene biosynthesis
US5576338A (en) * 1995-02-15 1996-11-19 Merck Frosst Canada, Inc. Bis (biaryl) compounds as inhibitors of leukotriene biosynthesis
GB9524137D0 (en) 1995-11-24 1996-01-24 Smithkline Beecham Spa Novel compounds
JPH115772A (ja) * 1997-04-25 1999-01-12 Takeda Chem Ind Ltd アミド誘導体、その製造法および用途
EP0975621A1 (en) * 1997-04-25 2000-02-02 Takeda Chemical Industries, Ltd. Cell differentiation inducing amide derivatives, their production and use
AU779874B2 (en) * 1999-10-15 2005-02-17 F. Hoffmann-La Roche Ag Benzodiazepine derivatives
TWI328009B (en) * 2003-05-21 2010-08-01 Glaxo Group Ltd Quinoline derivatives as phosphodiesterase inhibitors
US20060275835A1 (en) 2003-07-11 2006-12-07 Jacobson Marlene A Methods for identifying cell surface receptor protein modulators
CN1856307A (zh) 2003-09-23 2006-11-01 默克公司 喹啉钾通道抑制剂
US20070287716A1 (en) 2004-10-28 2007-12-13 Hu Essa H Pyrimidine and Quinoline Potentiators of Metabotropic Glutamate Receptors
JP2009510132A (ja) * 2005-10-05 2009-03-12 メルク フロスト カナダ リミテツド ロイコトリエン生合成の阻害剤としての置換キノリン
AR065093A1 (es) 2007-02-05 2009-05-13 Merck Frosst Canada Ltd Compuestos farmacéuticos inhibidores de la biosintesis de leucotrienos
CN101730684B (zh) * 2007-06-18 2013-07-24 吉瑞工厂 磺酰基-喹啉衍生物
WO2011153553A2 (en) 2010-06-04 2011-12-08 The Regents Of The University Of California Methods and compositions for kinase inhibition
WO2012083866A1 (en) 2010-12-22 2012-06-28 The Hong Kong Polytechnic University Quinoline derivatives as anti-cancer agents
US9278960B2 (en) 2011-11-03 2016-03-08 Merck Sharp & Dohme Corp. Quinoline carboxamide and quinoline carbonitrile derivatives as mGluR2-negative allosteric modulators, compositions, and their use

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