KR20070051340A - 폴리(adp-리보오스) 폴리머라제 억제제의 제조 방법 - Google Patents
폴리(adp-리보오스) 폴리머라제 억제제의 제조 방법 Download PDFInfo
- Publication number
- KR20070051340A KR20070051340A KR1020077006426A KR20077006426A KR20070051340A KR 20070051340 A KR20070051340 A KR 20070051340A KR 1020077006426 A KR1020077006426 A KR 1020077006426A KR 20077006426 A KR20077006426 A KR 20077006426A KR 20070051340 A KR20070051340 A KR 20070051340A
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- formula
- fluoro
- amino
- indole
- Prior art date
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- 0 CN(*)Cc(cc1)ccc1C#Cc(c([N+]([O-])=O)cc(F)c1)c1C(OC)=O Chemical compound CN(*)Cc(cc1)ccc1C#Cc(c([N+]([O-])=O)cc(F)c1)c1C(OC)=O 0.000 description 2
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
- C07D487/06—Peri-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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Saccharide Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
Claims (8)
- a) 하기 화학식 II의 화합물을 하기 화학식 III의 화합물과 소노가시라 (Sonogashira) 커플링시켜 하기 화학식 IV의 화합물을 형성하는 단계;b) 화학식 IV의 화합물을 환원시켜 하기 화학식 V의 화합물을 생성하는 단계;c) 화학식 V의 화합물을 하기 화학식 VI의 화합물로 전환시키는 단계; 및d) 화학식 VI의 화합물을 하기 화학식 I의 화합물로 전환시키는 단계를 포함하는, 화학식 Ⅰ의 화합물의 제조 방법.<화학식 Ⅰ><화학식 II><화학식 III><화학식 IV><화학식 V><화학식 VI>식 중,R1은 H; 시아노; 임의로 치환되거나 치환되지 않은 알킬, 알케닐, 알키닐, 시클로알킬, 헤테로시클로알킬, 아릴 또는 헤테로아릴기; 또는 --C(O)--R5 [여기에서, R5는 H; 임의로 치환되거나 치환되지 않은 알킬, 알케닐, 알키닐, 시클로알킬, 헤테로시클로알킬, 아릴 또는 헤테로아릴기; 또는 OR6 또는 NR6R7 (여기에서, R6 및 R7은 각각 독립적으로 H, 또는 임의로 치환되거나 치환되지 않은 알킬, 알케닐, 알키닐, 시클로알킬, 헤테로시클로알킬, 아릴, 또는 헤테로아릴기임)임]이고;R2은 H 또는 알킬이고;R3은 H 또는 알킬이고;R4은 H, 할로겐 또는 알킬이고;X는 할로겐 또는 CF3SO2-O-이다.
- 제1항에 있어서, 단계 c)가 CuI-촉진성 인돌 형성을 포함하는 것인 방법.
- 제3항에 있어서, X가 CF3SO2-O-인 방법.
- 제3항에 있어서, X가 브롬인 방법.
- 제3항에 있어서,a) 5-플루오로-2-{4-[(메톡시카르보닐-메틸-아미노)-메틸]-페닐에티닐}-3-니트로-벤조산 메틸 에스테르를 3-아미노-5-플루오로-2-{4-[(메톡시카르보닐-메틸-아미노)-메틸]-페닐에티닐}-벤조산 메틸 에스테르로 환원시키는 단계;b) 3-아미노-5-플루오로-2-{4-[(메톡시카르보닐-메틸-아미노)-메틸]-페닐에티닐}-벤조산 메틸 에스테르를 6-플루오로-2-{4-[(메톡시카르보닐-메틸-아미노)-메틸]-페닐}-1H-인돌-4-카르복실산 메틸 에스테르로 전환시키는 단계;c) 6-플루오로-2-{4-[(메톡시카르보닐-메틸-아미노)-메틸]-페닐}-1H-인돌-4-카르복실산 메틸 에스테르를 N,N-디메틸-2-니트로에틸렌아민으로 처리하여 6-플루오로-2-{4-[(메톡시카르보닐-메틸-아미노)-메틸]-페닐}-3-((E)-2-니트로-비닐)-1H-인돌-4-카르복실산 메틸 에스테르를 생성하는 단계;d) 6-플루오로-2-{4-[(메톡시카르보닐-메틸-아미노)-메틸]-페닐}-3-((E)-2-니트로-비닐)-1H-인돌-4-카르복실산 메틸 에스테르를 6-플루오로-2-{4-[(메톡시카르보닐-메틸-아미노)-메틸]-페닐}-3-(2-니트로-에틸)-1H-인돌-4-카르복실산 메틸 에스테르로 환원시키는 단계;e) 6-플루오로-2-{4-[(메톡시카르보닐-메틸-아미노)-메틸]-페닐}-3-(2-니트로-에틸)-1H-인돌-4-카르복실산 메틸 에스테르를 [4-(8-플루오로-6-옥소-3,4,5,6-테트라히드로-1H-아제피노[5,4,3-cd]인돌-2-일)-벤질]-메틸-카르밤산 메틸 에스테 르로 전환시키는 단계; 및f) [4-(8-플루오로-6-옥소-3,4,5,6-테트라히드로-1H-아제피노[5,4,3-cd]인돌-2-일)-벤질]-메틸-카르밤산 메틸 에스테르를 탈보호시켜 8-플루오로-2-{4-[(메틸아미노)메틸]페닐}-1,3,4,5-테트라히드로-6H-아제피노[5,4,3-cd]인돌-6-온을 생성하는 단계를 더 포함하는 방법.
- 제6항에 있어서, 단계 b)가 CuI-촉진성 인돌 형성을 포함하는 것인 방법.
- 제6항에 있어서, 단계 e)가 수소화를 포함하는 것인 방법.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US61245704P | 2004-09-22 | 2004-09-22 | |
US60/612,457 | 2004-09-22 | ||
PCT/IB2005/002881 WO2006033003A1 (en) | 2004-09-22 | 2005-09-12 | Method of preparing poly(adp-ribose) polymerases inhibitors |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020087026159A Division KR20080097497A (ko) | 2004-09-22 | 2005-09-12 | 폴리(adp-리보오스) 폴리머라제 억제제의 제조 방법 |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20070051340A true KR20070051340A (ko) | 2007-05-17 |
KR100876520B1 KR100876520B1 (ko) | 2008-12-31 |
Family
ID=35432127
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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KR1020077006426A KR100876520B1 (ko) | 2004-09-22 | 2005-09-12 | 폴리(adp-리보오스) 폴리머라제 억제제의 제조 방법 |
KR1020087026159A KR20080097497A (ko) | 2004-09-22 | 2005-09-12 | 폴리(adp-리보오스) 폴리머라제 억제제의 제조 방법 |
Family Applications After (1)
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KR1020087026159A KR20080097497A (ko) | 2004-09-22 | 2005-09-12 | 폴리(adp-리보오스) 폴리머라제 억제제의 제조 방법 |
Country Status (24)
Country | Link |
---|---|
US (1) | US7323562B2 (ko) |
EP (1) | EP1794163B1 (ko) |
JP (1) | JP4966858B2 (ko) |
KR (2) | KR100876520B1 (ko) |
CN (1) | CN101027306B (ko) |
AT (1) | ATE452895T1 (ko) |
AU (1) | AU2005286187B2 (ko) |
BR (1) | BRPI0515255A (ko) |
CA (1) | CA2580833C (ko) |
CY (1) | CY1109945T1 (ko) |
DE (1) | DE602005018506D1 (ko) |
DK (1) | DK1794163T3 (ko) |
ES (1) | ES2337275T3 (ko) |
HK (1) | HK1112454A1 (ko) |
IL (1) | IL181322A (ko) |
MX (1) | MX2007003311A (ko) |
NO (1) | NO339357B1 (ko) |
NZ (1) | NZ553201A (ko) |
PL (1) | PL1794163T3 (ko) |
PT (1) | PT1794163E (ko) |
RU (1) | RU2344138C2 (ko) |
SI (1) | SI1794163T1 (ko) |
WO (1) | WO2006033003A1 (ko) |
ZA (1) | ZA200701266B (ko) |
Cited By (1)
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WO2023013974A1 (ko) * | 2021-08-03 | 2023-02-09 | 고려대학교 산학협력단 | Parp 저해제인 루카파립과 그 중간체의 신규한 제조방법 |
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WO2017013593A1 (en) | 2015-07-22 | 2017-01-26 | Lupin Limited | Isoquinolinone derivatives as parp inhibitors |
KR101896567B1 (ko) | 2015-07-23 | 2018-09-07 | 인스티튜트 큐리 | 암 치료를 위한 디베이트 분자와 parp 억제제의 병용 용도 |
GB201519573D0 (en) | 2015-11-05 | 2015-12-23 | King S College London | Combination |
EP3573990A1 (en) | 2017-01-24 | 2019-12-04 | Assia Chemical Industries Ltd. | Solid state forms of rucaparib and of rucaparib salts |
WO2018162439A1 (en) | 2017-03-08 | 2018-09-13 | Onxeo | New predictive biomarker for the sensitivity to a treatment of cancer with a dbait molecule |
IT201700085789A1 (it) * | 2017-07-26 | 2019-01-26 | Olon Spa | Metodo per la preparazione di rucaparib ad elevata purezza |
US11220507B2 (en) | 2017-12-15 | 2022-01-11 | Advitech Advisory And Technologies Sa | Process for the preparation of rucaparib and novel synthesis intermediates |
WO2019130229A1 (en) | 2017-12-28 | 2019-07-04 | Mylan Laboratories Ltd | Methods and intermediates for preparing rucaparib |
JP7356450B2 (ja) | 2018-01-05 | 2023-10-04 | サイブレクサ 1・インコーポレイテッド | 酸性または低酸素の疾患組織を含む疾患の治療のための化合物、組成物、及び方法 |
CN110229162B (zh) * | 2018-03-05 | 2020-08-11 | 新发药业有限公司 | 一种瑞卡帕布的简便制备方法 |
CA3092779A1 (en) | 2018-03-13 | 2019-09-19 | Onxeo | A dbait molecule against acquired resistance in the treatment of cancer |
KR102548191B1 (ko) * | 2018-04-09 | 2023-06-28 | 상하이테크 유니버시티 | 표적 단백질 분해 화합물, 이의 항종양 응용, 이의 중간체 및 중간체의 응용 |
CN108752353B (zh) * | 2018-04-28 | 2020-05-08 | 程春晓 | 抗卵巢癌药物Rucaparib关键中间体1408282‐26‐7的制备方法 |
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EP4182318A1 (en) | 2020-07-14 | 2023-05-24 | Assia Chemical Industries Ltd | Solid state forms of rucaparib salts |
WO2022090938A1 (en) | 2020-10-31 | 2022-05-05 | Rhizen Pharmaceuticals Ag | Phthalazinone derivatives useful as parp inhibitors |
JP2024515338A (ja) | 2021-04-08 | 2024-04-09 | ライゼン ファーマシューティカルズ アーゲー | ポリ(adp-リボース)ポリメラーゼの阻害剤 |
KR102638023B1 (ko) * | 2021-08-03 | 2024-02-19 | 고려대학교 산학협력단 | 신규한 루카파립의 제조방법 |
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CN114874127B (zh) * | 2022-05-23 | 2023-06-09 | 中国药科大学 | 一种二氟羰基化吲哚酮类化合物的制备方法 |
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2005
- 2005-09-12 KR KR1020077006426A patent/KR100876520B1/ko active IP Right Grant
- 2005-09-12 AU AU2005286187A patent/AU2005286187B2/en active Active
- 2005-09-12 PT PT05783113T patent/PT1794163E/pt unknown
- 2005-09-12 DK DK05783113.3T patent/DK1794163T3/da active
- 2005-09-12 ES ES05783113T patent/ES2337275T3/es active Active
- 2005-09-12 JP JP2007532991A patent/JP4966858B2/ja active Active
- 2005-09-12 BR BRPI0515255-0A patent/BRPI0515255A/pt not_active Application Discontinuation
- 2005-09-12 RU RU2007106973/04A patent/RU2344138C2/ru active
- 2005-09-12 SI SI200530924T patent/SI1794163T1/sl unknown
- 2005-09-12 WO PCT/IB2005/002881 patent/WO2006033003A1/en active Application Filing
- 2005-09-12 KR KR1020087026159A patent/KR20080097497A/ko not_active Application Discontinuation
- 2005-09-12 PL PL05783113T patent/PL1794163T3/pl unknown
- 2005-09-12 NZ NZ553201A patent/NZ553201A/en unknown
- 2005-09-12 MX MX2007003311A patent/MX2007003311A/es active IP Right Grant
- 2005-09-12 CA CA2580833A patent/CA2580833C/en active Active
- 2005-09-12 AT AT05783113T patent/ATE452895T1/de active
- 2005-09-12 EP EP05783113A patent/EP1794163B1/en active Active
- 2005-09-12 CN CN2005800320140A patent/CN101027306B/zh active Active
- 2005-09-12 DE DE602005018506T patent/DE602005018506D1/de active Active
- 2005-09-21 US US11/233,845 patent/US7323562B2/en active Active
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2007
- 2007-02-13 IL IL181322A patent/IL181322A/en active IP Right Grant
- 2007-02-13 ZA ZA200701266A patent/ZA200701266B/en unknown
- 2007-02-15 NO NO20070858A patent/NO339357B1/no unknown
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2008
- 2008-01-30 HK HK08101150.6A patent/HK1112454A1/xx unknown
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- 2010-03-22 CY CY20101100269T patent/CY1109945T1/el unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023013974A1 (ko) * | 2021-08-03 | 2023-02-09 | 고려대학교 산학협력단 | Parp 저해제인 루카파립과 그 중간체의 신규한 제조방법 |
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