TWI455938B - 碳酸啶衍生物及其醫藥組成物 - Google Patents
碳酸啶衍生物及其醫藥組成物 Download PDFInfo
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- TWI455938B TWI455938B TW098126682A TW98126682A TWI455938B TW I455938 B TWI455938 B TW I455938B TW 098126682 A TW098126682 A TW 098126682A TW 98126682 A TW98126682 A TW 98126682A TW I455938 B TWI455938 B TW I455938B
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/04—Drugs for disorders of the respiratory system for throat disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pulmonology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
Claims (24)
- 一種通式(I)之化合物 其中:A可為芳基、或雜芳基、或芳基烷基、或雜芳基烷基、或式(a)基團 其中R3 及R4 為相同或相異,且可分別選自於包含H、(C3 -C8 )-環烷基、芳基或雜芳基之組群,其中該芳基或雜芳基視需要可經以鹵原子或以分別選自於OH、O-(C1 -C10 )-烷基、酮基(=O)、SH、S-(C1 -C10 )-烷基、NO2 、CN、CONH2 、COOH、(C1 -C10 )-烷氧羰基、(C1 -C10 )-烷基硫烷基、(C1 -C10 )-烷基亞磺醯基、(C1 -C10 )-烷基磺醯基、(C1 -C10 )-烷基、及(C1 -C10 )-烷氧基之一個或數個取代基取代;或當R3 及R4 兩者分別為芳基或雜芳基時,其可經由一Y基團鏈接,該Y基團可為(CH2 )n ,n=0-2,其中當n=0時,Y為單鍵,形成三環之環系,其中(CH2 )n 之碳原子可經以選自於O、S、N之雜原子取代,但限 制條件為R3 及R4 不可皆為H;R為選自於下列之殘基:‧(C1 -C10 )-烷基、(C2 -C10 )-烯基及(C2 -C10 )-炔基,其視需要可經以選自於下列之基團取代:‧選自於NH2 、NR1 R2 、CONR1 R2 、NR2 COR1 、OH、SOR1 、SO2 R1 、SH、CN、NO2 及環脂族化合物之基團;‧Z-R1 ,其中Z係選自於CO、O、COO、OCO、SO2 、S、SO、COS及SCO或其為一鍵結及‧(C3 -C8 )-環烷基;R1 為選自於下列之殘基:‧視需要可經以分別選自於OH、酮基(=O)、SH、NO2 、CN、CONH2 、NR2 CO-(C1 -CX )-烷基、COOH、(C1 -C10 )-烷氧羰基、(C1 -C10 )-烷基硫烷基、(C1 -C10 )-烷基亞磺醯基、(C1 -C10 )-烷基磺醯基、(C1 -C10 )-烷基及(C1 -C10 )-烷氧基NR2 CO-(C1 -C10 )-烷基之一個或數個取代基取代之環脂族化合物;‧視需要可經以NR2 CO-(C1 -C10 )-烷基取代之芳基;及‧視需要可經以NR2 CO-(C1 -C10 )-烷基、(C1 -C10 )-烷基、O-(C1 -C10 )-烷基或鹵原子取代之雜芳基;R2 為選自於H、苯氧羰基、苄氧羰基、(C1 -C10 )-烷氧羰基、(C1 -C10 )-烷基羰基、(C1 -C10 )-烷基磺醯基及(C1 -C10 )-烷基之殘基;X- 為生理上可接受之陰離子, 其中:環脂族化合物包括(C3 -C8 )-環烷基、二環烷基及三環烷基、及環狀非芳香族烴不飽和基之化合物;芳基係指具有5至20個環原子之一環、二環或三環環系,其中至少一個環為芳香環,該等環中之一個或多個氫原子視需要可經以一個或多個鹵原子或苯基取代;雜芳基係指具有5至20個環原子之一環、二環或三環環系,其中至少一個環為芳香環及其中至少一個環原子為選自N、S或O之雜原子,該等環中之一個或多個氫原子視需要可經以一個或多個鹵原子取代;芳基烷基係指視需要可經以具有5至20個環原子之一環、二環或三環環系取代之(C1 -C4 )-烷基,該等環中之一個或多個氫原子視需要可經以一個或多個鹵原子取代;及雜芳基烷基係指視需要可經以具有5至20個環原子之一環、二環或三環環系取代之(C1 -C4 )-烷基,其中至少一個環為芳香環及其中至少一個環原子為選自N、S或O之雜原子,該等環中之一個或多個氫原子視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第1項之化合物,其中,R為經以-Z-R1 取代之(C1 -C6 )-烷基。
- 如申請專利範圍第1項之化合物,其中,R為經以-Z-R1 取代之(C1 -C6 )-烷基,其中Z為O、CO或一鍵結,及R1 為芳 基或雜芳基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第1項之化合物,其中,R為CH2 ,Z為CO及R1 為噻吩基,其係根據式(II)所示:
- 如申請專利範圍第4項之化合物,其中,A為芳基、或雜芳基、或芳基烷基、或雜芳基烷基、或式(a)基團 其中R3 及R4 兩者分別為芳基或雜芳基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第4項之化合物,其中,A為式(a)基團,其中R3 及R4 皆為苯基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第4項之化合物,其中,A為式(a)基團,其中R3 及R4 兩者分別為苯基,及其係經由一Y基團鏈接,該Y基團可為(CH2 )n ,n=0-2,其中當n=0時,Y為單鍵,形成式(b)三環之環系 其中(CH2 )n 之碳原子可經以選自於O、S、N之雜原子取代。
- 如申請專利範圍第4項之化合物,其中,A為9H-芴-9-基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第4項之化合物,其中,A為苄基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第4項之化合物,其中,A為聯苯甲基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第4項之化合物,其中,A為苯硫基甲基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第1項之化合物,其中,R為丙基,且係經以Z-R1 基團取代,其中Z為O及R1 為苯基,其係根據式(III)所示:
- 如申請專利範圍第12項之化合物,其中,A為芳基、或雜芳基、或芳基烷基、或雜芳基烷基、或式(a)基團,其 中R3 及R4 兩者分別為芳基或雜芳基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第12項之化合物,其中,A為式(a)基團,其中R3 及R4 皆為苯基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第12項之化合物,其中,A為式(a)基團,其中R3 及R4 兩者分別為芳基或雜芳基,及其係經由一Y基團鏈接,該Y基團可為(CH2 )n ,n=0-2,其中當n=0時,Y為單鍵,形成式(b)三環之環系 其中(CH2 )n 之碳原子可經以選自於O、S、N之雜原子取代。
- 如申請專利範圍第12項之化合物,其中,A為9H-芴-9-基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第12項之化合物,其中,A為苄基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第12項之化合物,其中,A為聯苯甲基,其視需要可經以一個或多個鹵原子取代。
- 如申請專利範圍第12項之化合物,其中,A為苯硫基甲基,其視需要可經以一個或多個鹵原子取代。
- 一種醫藥組成物,包含申請專利範圍第1至19項中任一項之化合物,混合一種或多種醫藥上可接受之載劑及/或賦形劑。
- 一種以申請專利範圍第1至19項中任一項之化合物用於製造預防及/或治療任一種支氣管阻塞疾病或發炎疾病之藥物的用途。
- 如申請專利範圍第21項之用途,其中,該疾病包含氣喘、慢性支氣管炎及慢性阻塞性肺疾(COPD)。
- 一種裝置,其為包含申請專利範圍第20項之醫藥組成物之單劑或多劑乾粉吸入器、計量劑量吸入器或軟霧霧化器。
- 一種製備申請專利範圍第1項式(I)化合物之方法,包含下列步驟:(i)將式(II)胺醇 與1,1’-羰基二咪唑反應獲得式(III)咪唑衍生物; (ii)然後與式(IV)醇反應, 因而獲得式(V)化合物; (iii)然後利用烷化劑RX烷化,獲得式(I)第四銨鹽。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP08162066A EP2154136A1 (en) | 2008-08-08 | 2008-08-08 | Quinuclidine carbonate derivatives and medicinal compositions thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
TW201011022A TW201011022A (en) | 2010-03-16 |
TWI455938B true TWI455938B (zh) | 2014-10-11 |
Family
ID=40228074
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW098126682A TWI455938B (zh) | 2008-08-08 | 2009-08-06 | 碳酸啶衍生物及其醫藥組成物 |
Country Status (32)
Country | Link |
---|---|
US (3) | US8039483B2 (zh) |
EP (2) | EP2154136A1 (zh) |
JP (1) | JP2011530489A (zh) |
KR (1) | KR20110044221A (zh) |
CN (1) | CN102112474B (zh) |
AR (1) | AR072994A1 (zh) |
AT (1) | ATE551341T1 (zh) |
AU (1) | AU2009278306B2 (zh) |
CA (1) | CA2733380A1 (zh) |
CO (1) | CO6351790A2 (zh) |
CY (1) | CY1112724T1 (zh) |
DK (1) | DK2313404T3 (zh) |
EA (1) | EA019166B1 (zh) |
ES (1) | ES2384914T3 (zh) |
GE (1) | GEP20135744B (zh) |
HK (1) | HK1156032A1 (zh) |
HR (1) | HRP20120394T1 (zh) |
IL (1) | IL211103A (zh) |
JO (1) | JO2831B1 (zh) |
MA (1) | MA32622B1 (zh) |
ME (1) | ME01283A (zh) |
MX (1) | MX2011001504A (zh) |
MY (1) | MY156332A (zh) |
NZ (1) | NZ590987A (zh) |
PL (1) | PL2313404T3 (zh) |
PT (1) | PT2313404E (zh) |
RS (1) | RS52370B (zh) |
SI (1) | SI2313404T1 (zh) |
TW (1) | TWI455938B (zh) |
UA (1) | UA102857C2 (zh) |
WO (1) | WO2010015324A1 (zh) |
ZA (1) | ZA201100963B (zh) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009079078A1 (en) | 2007-12-14 | 2009-06-25 | Labogroup S.A.S. | Delivering aerosolizable food products |
EP2154136A1 (en) | 2008-08-08 | 2010-02-17 | CHIESI FARMACEUTICI S.p.A. | Quinuclidine carbonate derivatives and medicinal compositions thereof |
EP2206712A1 (en) | 2008-12-23 | 2010-07-14 | CHIESI FARMACEUTICI S.p.A. | "Alkaloid aminoester derivatives and medicinal composition thereof" |
HUE038555T2 (hu) | 2010-04-21 | 2018-10-29 | Chiesi Farm Spa | Eljárás csökkentett elektrosztatikus töltéssel rendelkezõ részecskék elõállítására |
EP2585458B1 (en) | 2010-06-22 | 2015-01-07 | Chiesi Farmaceutici S.p.A. | Alkaloid aminoester derivatives and medicinal compositions thereof |
CA2803416A1 (en) | 2010-06-22 | 2011-12-29 | Chiesi Farmaceutici S.P.A. | Alkaloid aminoester derivatives and medicinal composition thereof |
CA2803459A1 (en) | 2010-06-22 | 2011-12-29 | Chiesi Farmaceutici S.P.A. | Alkaloid aminoester derivatives and medicinal compositions thereof |
BR112013007022B1 (pt) | 2010-09-30 | 2019-10-15 | Chiesi Farmaceutici S.P.A | Uso de estearato de magnésio |
EP2630145A1 (en) * | 2010-10-20 | 2013-08-28 | Chiesi Farmaceutici S.p.A. | Carbonate derivatives for the treatment of cough |
CN103221390B (zh) | 2010-11-26 | 2015-06-03 | 奇斯药制品公司 | 甘氨酸衍生物及其医药组合物 |
PT2685986T (pt) * | 2011-03-18 | 2020-03-05 | Genzyme Corp | Inibidor de glicosilceramida-sintase |
EP2702041A1 (en) * | 2011-04-29 | 2014-03-05 | Chiesi Farmaceutici S.p.A. | Alkaloid ester and carbamate derivatives and medicinal compositions thereof |
WO2013098145A1 (en) | 2011-12-30 | 2013-07-04 | Chiesi Farmaceutici S.P.A. | Quinuclidine esters of 1-azaheterocyclylacetic acid as antimuscarinic agents, process for their preparation and medicinal compositions thereof |
MA37975B2 (fr) * | 2012-09-11 | 2021-03-31 | Genzyme Corp | Inhibiteurs de synthase de glucosylcéramide |
US9427376B2 (en) | 2013-10-10 | 2016-08-30 | Chiesi Farmaceutici S.P.A. | Process for preparing pharmaceutical formulations for inhalation comprising a high-dosage strength active ingredient |
CA3166777A1 (en) | 2020-02-03 | 2021-08-12 | Nigel Patrick Somerville CRAWFORD | Methods for treating neurological symptoms associated with lysosomal storage diseases |
TW202220648A (zh) | 2020-07-24 | 2022-06-01 | 美商健臻公司 | 包含芬谷司他(venglustat)之醫藥組合物 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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EP1882691A1 (en) * | 2006-07-26 | 2008-01-30 | CHIESI FARMACEUTICI S.p.A. | Quinuclidine derivatives as M3 antagonists |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
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ES2165768B1 (es) * | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
BR0116450A (pt) | 2000-12-22 | 2003-09-30 | Almirall Prodesfarma Ag | Composto, processos para a preparação de um carbamato, e para produzir um sal, composição farmacêutica, uso de um composto ou de uma composição farmacêutica, e, produto de combinação |
EP1383730A2 (en) * | 2001-04-03 | 2004-01-28 | Aryx Therapeutics | Anticholinergic compounds and methods of use |
US7452904B2 (en) | 2001-12-20 | 2008-11-18 | Chiesi Farmaceutici S.P.A. | 1-alkyl-1-azoniabicyclo' 2.2.2 octane carbamate derivatives and their use as muscarinic receptor antagonists |
EP2154136A1 (en) | 2008-08-08 | 2010-02-17 | CHIESI FARMACEUTICI S.p.A. | Quinuclidine carbonate derivatives and medicinal compositions thereof |
EP2206712A1 (en) | 2008-12-23 | 2010-07-14 | CHIESI FARMACEUTICI S.p.A. | "Alkaloid aminoester derivatives and medicinal composition thereof" |
BR112012032330A2 (pt) | 2010-06-22 | 2016-11-08 | Chiesi Farma Spa | formulação em pó seco inalável, uso de uma formulação em pó seco, inalador de pó seco e embalagem |
EP2630145A1 (en) | 2010-10-20 | 2013-08-28 | Chiesi Farmaceutici S.p.A. | Carbonate derivatives for the treatment of cough |
US20120220557A1 (en) | 2011-02-17 | 2012-08-30 | Chiesi Farmaceutici S.P.A. | Liquid propellant-free formulation comprising an antimuscarinic drug |
EP2702041A1 (en) | 2011-04-29 | 2014-03-05 | Chiesi Farmaceutici S.p.A. | Alkaloid ester and carbamate derivatives and medicinal compositions thereof |
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2008
- 2008-08-08 EP EP08162066A patent/EP2154136A1/en not_active Withdrawn
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2009
- 2009-07-21 EA EA201100161A patent/EA019166B1/ru not_active IP Right Cessation
- 2009-07-21 WO PCT/EP2009/005272 patent/WO2010015324A1/en active Application Filing
- 2009-07-21 PL PL09777321T patent/PL2313404T3/pl unknown
- 2009-07-21 MY MYPI2011000542A patent/MY156332A/en unknown
- 2009-07-21 UA UAA201101383A patent/UA102857C2/ru unknown
- 2009-07-21 EP EP09777321A patent/EP2313404B1/en active Active
- 2009-07-21 ES ES09777321T patent/ES2384914T3/es active Active
- 2009-07-21 RS RS20120262A patent/RS52370B/en unknown
- 2009-07-21 CN CN200980130187.4A patent/CN102112474B/zh active Active
- 2009-07-21 ME MEP-2011-24A patent/ME01283A/me unknown
- 2009-07-21 DK DK09777321.2T patent/DK2313404T3/da active
- 2009-07-21 MX MX2011001504A patent/MX2011001504A/es active IP Right Grant
- 2009-07-21 JP JP2011521454A patent/JP2011530489A/ja active Pending
- 2009-07-21 AT AT09777321T patent/ATE551341T1/de active
- 2009-07-21 NZ NZ590987A patent/NZ590987A/xx not_active IP Right Cessation
- 2009-07-21 AU AU2009278306A patent/AU2009278306B2/en not_active Ceased
- 2009-07-21 GE GEAP200912093A patent/GEP20135744B/en unknown
- 2009-07-21 CA CA2733380A patent/CA2733380A1/en not_active Abandoned
- 2009-07-21 SI SI200930266T patent/SI2313404T1/sl unknown
- 2009-07-21 KR KR1020117002974A patent/KR20110044221A/ko not_active Application Discontinuation
- 2009-07-21 PT PT09777321T patent/PT2313404E/pt unknown
- 2009-07-30 US US12/512,262 patent/US8039483B2/en active Active
- 2009-08-06 JO JO2009296A patent/JO2831B1/en active
- 2009-08-06 TW TW098126682A patent/TWI455938B/zh not_active IP Right Cessation
- 2009-08-07 AR ARP090103053A patent/AR072994A1/es unknown
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2011
- 2011-02-07 CO CO11013721A patent/CO6351790A2/es active IP Right Grant
- 2011-02-07 ZA ZA2011/00963A patent/ZA201100963B/en unknown
- 2011-02-07 IL IL211103A patent/IL211103A/en not_active IP Right Cessation
- 2011-03-08 MA MA33683A patent/MA32622B1/fr unknown
- 2011-08-26 US US13/219,109 patent/US8440690B2/en active Active
- 2011-09-14 US US13/232,415 patent/US8404712B2/en active Active
- 2011-10-03 HK HK11110402.8A patent/HK1156032A1/xx unknown
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2012
- 2012-05-10 HR HRP20120394AT patent/HRP20120394T1/hr unknown
- 2012-05-11 CY CY20121100443T patent/CY1112724T1/el unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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EP1882691A1 (en) * | 2006-07-26 | 2008-01-30 | CHIESI FARMACEUTICI S.p.A. | Quinuclidine derivatives as M3 antagonists |
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