TWI455937B - 具有抗菌活性之２－羥乙基－１ｈ－喹啉－２－酮衍生物及其氮雜等排類似物 - Google Patents

具有抗菌活性之２－羥乙基－１ｈ－喹啉－２－酮衍生物及其氮雜等排類似物 Download PDF

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TWI455937B
TWI455937B TW099110909A TW99110909A TWI455937B TW I455937 B TWI455937 B TW I455937B TW 099110909 A TW099110909 A TW 099110909A TW 99110909 A TW99110909 A TW 99110909A TW I455937 B TWI455937 B TW I455937B
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Taiwan
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compound
methoxy
hydroxy
ethyl
amino
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TW099110909A
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TW201040182A (en
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Christian Hubschwerlen
Georg Rueedi
Jean-Philippe Surivet
Acklin Cornelia Zumbrunn
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Actelion Pharmaceuticals Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—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
    • 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
    • C07D491/04—Ortho-condensed systems
    • C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
    • 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
    • A61K31/436—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 six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A61P31/06—Antibacterial agents for tuberculosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D497/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms
    • C07D497/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D497/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Claims (14)

  1. 一種式I化合物或該化合物之醫藥上可接受的鹽， 其中：R1 表示(C1 -C4 )烷氧基；U及V各表示CH，且W表示CH或N，或U表示N，V表示CH，且W表示CH或N，或U及V各表示N，且W表示CH；當W表示CH時，R2 表示氫或氟，或當W表示N時，R2 表示氫；A表示O或CH2 ；Y表示CH或N；Q表示O或S；及n表示0或1。
  2. 如請求項1之式I化合物或該化合物之醫藥上可接受的鹽，其係式Ip化合物： 其中R1 表示(C1 -C4 )烷氧基；U及W各獨立地表示CH或N；A表示O或CH2 ；Y表示CH或N；及Q表示O或S。
  3. 如請求項1或2之式I化合物或該化合物之醫藥上可接受的鹽，其中Y表示CH。
  4. 如請求項1或2之式I化合物或該化合物之醫藥上可接受的鹽，其中Q表示O。
  5. 如請求項1或2之式I化合物或該化合物之醫藥上可接受的鹽，其中R1 表示甲氧基。
  6. 如請求項1或2之式I化合物或該化合物之醫藥上可接受的鹽，其中A表示O。
  7. 如請求項1或2之式I化合物或該化合物之醫藥上可接受的鹽，其中A表示CH2 。
  8. 如請求項1或2之式I化合物或該化合物之醫藥上可接受的鹽，其中n表示1。
  9. 如請求項1之式I化合物或該化合物之醫藥上可接受的鹽，其中：R1 表示甲氧基；U表示N，而V表示CH且W表示N，或V表示N且W表示CH；R2 表示氫；A表示O或CH2 ；Y表示CH；Q表示O或S；及n表示1。
  10. 如請求項1之式I化合物或該化合物之醫藥上可接受的鹽，其選自以下化合物：1-((S)-2-{(2S,5R)-5-[(2,3-二氫-4-氧雜-1-硫雜-6-氮雜-萘-7-基甲基)-胺基]-四氫-哌喃-2-基}-2-羥基-乙基)-7-甲氧基-1H-[1,8]萘啶-2-酮；1-((2S)-2-{(2S,5R)-5-[(2,3-二氫-[1,4]二氧雜環己烯并[2,3-c]吡啶-7-基甲基)-胺基]-四氫-哌喃-2-基}-2-羥基-乙基)-7-甲氧基-1H-[1,8]萘啶-2-酮；1-((2S)-2-{(2S,5R)-5-[(2,3-二氫-[1,4]二氧雜環己烯并[2,3-c]吡啶-7-基甲基)-胺基]-四氫-哌喃-2-基}-2-羥基-乙基)-7-甲氧基-1H-喹噁啉-2-酮；4-((2S)-2-{(2S,5R)-5-[(2,3-二氫-[1,4]二氧雜環己烯并[2,3-c]吡啶-7-基甲基)-胺基]-四氫-哌喃-2-基}-2-羥基-乙基)-6-甲氧基-4H-吡啶并[2,3-b]吡嗪-3-酮； 1-((2S)-2-{(2S,5R)-5-[(6,7-二氫-[1,4]二氧雜環己烯并[2,3-c]噠嗪-3-基甲基)-胺基]-四氫-哌喃-2-基}-2-羥基-乙基)-7-甲氧基-1H-[1,8]萘啶-2-酮；1-((2R)-2-{4-[(2,3-二氫-[1,4]二氧雜環己烯并[2,3-c]吡啶-7-基甲基)-胺基]-環己基}-2-羥基-乙基)-7-甲氧基-1H-[1,8]萘啶-2-酮；1-((2R)-2-{4-[(2,3-二氫-[1,4]二氧雜環己烯并[2,3-c]吡啶-7-基甲基)-胺基]-環己基}-2-羥基-乙基)-7-甲氧基-1H-喹噁啉-2-酮；1-((2S)-2-{(2S,5R)-5-[(6,7-二氫-8-氧雜-5-硫雜-1,2-二氮雜-萘-3-基甲基)-胺基]-四氫-哌喃-2-基}-2-羥基-乙基)-7-甲氧基-1H-[1,8]萘啶-2-酮；1-((2S)-2-羥基-2-{(2S,5R)-5-[(3-氧雜-1-硫雜-5-氮雜-二氫化茚-6-基甲基)-胺基]-四氫-哌喃-2-基}-乙基)-7-甲氧基-1H-[1,8]萘啶-2-酮；3-氟-1-((2S)-2-羥基-2-{(2S,5R)-5-[(3-氧雜-1-硫雜-5-氮雜-二氫化茚-6-基甲基)-胺基]-四氫-哌喃-2-基}-乙基)-7-甲氧基-1H-[1,8]萘啶-2-酮；4-((2S)-2-{(2S,5R)-5-[(2,3-二氫-4-氧雜-1-硫雜-6-氮雜-萘-7-基甲基)-胺基]-四氫-哌喃-2-基}-2-羥基-乙基)-6-甲氧基-4H-吡啶并[2,3-b]吡嗪-3-酮；4-((2S)-2-{(2S,5R)-5-[(6,7-二氫-8-氧雜-5-硫雜-1,2-二氮雜-萘-3-基甲基)-胺基]-四氫-哌喃-2-基}-2-羥基-乙基)-6-甲氧基-4H-吡啶并[2,3-b]吡嗪-3-酮； 5-((2S)-2-{(2S,5R)-5-[(2,3-二氫-[1,4]二氧雜環己烯并[2,3-c]吡啶-7-基甲基)-胺基]-四氫-哌喃-2-基}-2-羥基-乙基)-3-甲氧基-5H-吡啶并[2,3-b]吡嗪-6-酮；5-((2S)-2-{(2S,5R)-5-[(2,3-二氫-4-氧雜-1-硫雜-6-氮雜-萘-7-基甲基)-胺基]-四氫-哌喃-2-基}-2-羥基-乙基)-3-甲氧基-5H-吡啶并[2,3-b]吡嗪-6-酮；5-((S)-2-{(2S,5R)-5-[(6,7-二氫-8-氧雜-5-硫雜-1,2-二氮雜-萘-3-基甲基)-胺基]-四氫-哌喃-2-基}-2-羥基-乙基)-3-甲氧基-5H-吡啶并[2,3-b]吡嗪-6-酮；或該化合物之醫藥上可接受的鹽。
  11. 一種醫藥組合物，其包含作為活性成分之如請求項1至10中任一項所定義之式I化合物或其醫藥上可接受的鹽，及至少一種治療上惰性賦形劑。
  12. 一種如請求項1至10中任一項所定義之式I化合物或其醫藥上可接受的鹽之用途，其係用於製備用於治療細菌感染之藥劑。
  13. 如請求項12之用途，其中該藥劑係用於治療選自由下列組成之群之細菌感染：呼吸道感染、中耳炎、腦膜炎、皮膚及軟組織感染、肺炎、菌血症、心內膜炎、腹腔內感染、胃腸感染、艱難梭狀桿菌(Clostridium difficile )感染、尿道感染、性傳播感染、外來物感染、骨髓炎、萊姆病、局部感染、眼部感染、結核病及熱帶病。
  14. 如請求項12之用途，其中該藥劑係用於治療選自由呼吸道感染、中耳炎、腦膜炎、皮膚及軟組織感染、肺炎及菌血症組成之群之細菌感染。
TW099110909A 2009-04-09 2010-04-08 具有抗菌活性之２－羥乙基－１ｈ－喹啉－２－酮衍生物及其氮雜等排類似物 TWI455937B (zh)

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AU (1) AU2010233387B2 (zh)
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Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR076222A1 (es) 2009-04-09 2011-05-26 Actelion Pharmaceuticals Ltd Derivados 2-hidroxietil-1h-quinolin-ona y sus analogos azaisotericos con actividad antibacteriana y composiciones farmaceuticas que los contienen
AU2012275499A1 (en) * 2011-06-27 2013-12-19 Kyorin Pharmaceutical Co., Ltd. Bridged bicyclic compounds for the treatment of bacterial infections
TW201313726A (zh) 2011-09-16 2013-04-01 Actelion Pharmaceuticals Ltd 製造合成之中間體之方法
TW201833120A (zh) 2017-02-17 2018-09-16 瑞士商愛杜西亞製藥有限公司 芳基噁唑啶酮抗生素化合物

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006137485A1 (ja) * 2005-06-24 2006-12-28 Toyama Chemical Co., Ltd. 新規な含窒素複素環化合物およびその塩

Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU1095611A1 (ru) * 1982-09-10 2007-06-27 Краснодарский ордена Трудового Красного Знамени политехнический институт Хлорид 5-хлорметил-2-этил-8-метил-4Н-м-диоксино-(4,5-с)-пиридиния, обладающий антимикробной активностью
EG20543A (en) * 1992-10-30 1999-07-31 Procter & Gamble Process for preparing of novel antimicrobial -5- (n-heterosubstituted amino) quinolones
WO1998007703A1 (fr) * 1996-08-22 1998-02-26 Meiji Seika Kaisha, Ltd. Derives quinoleine et agent psychotrope
GB0112834D0 (en) * 2001-05-25 2001-07-18 Smithkline Beecham Plc Medicaments
TW200406413A (en) * 2002-06-26 2004-05-01 Glaxo Group Ltd Compounds
US7691850B2 (en) 2004-06-15 2010-04-06 Glaxo Group Limited Antibacterial agents
CA2580621A1 (en) * 2004-09-24 2006-03-30 Actelion Pharmaceuticals Ltd New bicyclic antibiotics
US7981886B2 (en) * 2005-05-25 2011-07-19 Actelion Pharmaceutical Ltd. Antibiotics derivatives
MY150958A (en) * 2005-06-16 2014-03-31 Astrazeneca Ab Compounds for the treatment of multi-drug resistant bacterial infections
CN101341126A (zh) * 2005-10-13 2009-01-07 莫弗凯姆联合化学股份公司 具有抗菌活性的5-喹啉衍生物
EP2022793B1 (en) * 2006-05-26 2014-06-04 Toyama Chemical Co., Ltd. Novel heterocyclic compound or salt thereof and intermediate thereof
EP1992628A1 (en) 2007-05-18 2008-11-19 Glaxo Group Limited Derivatives and analogs of N-ethylquinolones and N-ethylazaquinolones
WO2008071981A1 (en) 2006-12-15 2008-06-19 Astrazeneca Ab Piperidines for the treatment of bacterial infections
TW200831517A (en) 2006-12-15 2008-08-01 Astrazeneca Ab Chemical compounds
WO2008071962A1 (en) 2006-12-15 2008-06-19 Astrazeneca Ab Pteridines and pyrimidinopyridines as antibacterial agents
WO2008071964A1 (en) 2006-12-15 2008-06-19 Astrazeneca Ab Naphthyridine bactericides
AU2008240764C1 (en) 2007-04-20 2011-10-20 Glaxo Group Limited Tricyclic nitrogen containing compounds as antibacterial agents
EP2005995A1 (en) 2007-06-22 2008-12-24 Glaxo Group Limited Heterocyclic compounds for the treatment of tuberculosis
WO2009001126A1 (en) 2007-06-27 2008-12-31 Astrazeneca Ab Substituted piperidine derivatives and their use as antibaterial agents
GB0800367D0 (en) 2008-01-09 2008-02-20 Glaxo Group Ltd Compounds
WO2009104159A1 (en) 2008-02-22 2009-08-27 Actelion Pharmaceuticals Ltd Oxazolidinone derivatives
BRPI0913093A2 (pt) * 2008-06-03 2018-02-06 Actelion Pharmaceuticals Ltd Compostos derivados de [4-(1-amino-etil)-cicloexil]- metil-amina e [6-(1-amino-etil)-tetraidro-piran-3-il]- metil-amina, medicamento, composição farmacêutica que contêm esse composto e uso dos mesmos
EP2344485B1 (en) 2008-10-10 2017-03-22 Actelion Pharmaceuticals Ltd Oxazolidinyl antibiotics
JP4955835B2 (ja) 2008-12-12 2012-06-20 アクテリオン ファーマシューティカルズ リミテッド ５−アミノ−２−（１−ヒドロキシ−エチル）−テトラヒドロピラン誘導体
AR076222A1 (es) 2009-04-09 2011-05-26 Actelion Pharmaceuticals Ltd Derivados 2-hidroxietil-1h-quinolin-ona y sus analogos azaisotericos con actividad antibacteriana y composiciones farmaceuticas que los contienen

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006137485A1 (ja) * 2005-06-24 2006-12-28 Toyama Chemical Co., Ltd. 新規な含窒素複素環化合物およびその塩

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AU2010233387B2 (en) 2015-01-15
CN102361875B (zh) 2014-08-20
ES2438742T3 (es) 2014-01-20
US8415375B2 (en) 2013-04-09
TW201040182A (en) 2010-11-16
AU2010233387A1 (en) 2011-11-24
CN102361875A (zh) 2012-02-22
BRPI1015310A8 (pt) 2017-12-26
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US20120040989A1 (en) 2012-02-16
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JP5639639B2 (ja) 2014-12-10
MX2011010358A (es) 2011-11-01
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RU2011145052A (ru) 2013-05-20
AR076222A1 (es) 2011-05-26
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WO2010116337A1 (en) 2010-10-14
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