BRPI0010559B8 - processo hemissintético e compostos intermediários - Google Patents

processo hemissintético e compostos intermediários

Info

Publication number
BRPI0010559B8
BRPI0010559B8 BRPI0010559A BRPI0010559A BRPI0010559B8 BR PI0010559 B8 BRPI0010559 B8 BR PI0010559B8 BR PI0010559 A BRPI0010559 A BR PI0010559A BR PI0010559 A BRPI0010559 A BR PI0010559A BR PI0010559 B8 BRPI0010559 B8 BR PI0010559B8
Authority
BR
Brazil
Prior art keywords
group
ring
keto
hemis
och
Prior art date
Application number
BRPI0010559A
Other languages
English (en)
Inventor
Francesch Andres
Cuevas Carmen
Fernandez Carolina
De La Calle Fernando
Manzanares Ignacio
Luis Chicharro Jose
Zarzuelo Maria
Perez Marta
Gallego Pilar
Original Assignee
Pharma Mar Sa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB9911345.8A external-priority patent/GB9911345D0/en
Priority claimed from GBGB9918178.6A external-priority patent/GB9918178D0/en
Priority claimed from GBGB9923632.5A external-priority patent/GB9923632D0/en
Priority claimed from GB0001063A external-priority patent/GB0001063D0/en
Application filed by Pharma Mar Sa filed Critical Pharma Mar Sa
Publication of BR0010559A publication Critical patent/BR0010559A/pt
Publication of BRPI0010559B1 publication Critical patent/BRPI0010559B1/pt
Publication of BRPI0010559B8 publication Critical patent/BRPI0010559B8/pt

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—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
    • C07D471/12—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 three hetero rings
    • C07D471/18—Bridged systems
    • 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
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—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
    • C07D471/22—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 systems contains four or more hetero rings
    • 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
    • C07D491/22—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 four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D515/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D515/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains four or more hetero rings
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Steroid Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

"processo hemissintético e compostos". são providos processos para preparação de um composto com uma estrutura de anel fundido da fórmula (xiv) que compreende uma ou mais reações de partida, a partir de um composto 21-ciano da fórmula (xvi), onde tipicamente: r^ 1^ é um grupo amidometileno ou um grupo aciloximetileno; r^ 5^ e r^ 8^ são independentemente escolhidos de -h, -oh ou -ococh~ 2~oh ou r^ 5^ e r^ 8^ são ambos ceto e o anel a é um anel p-benzoquinona; r^ 14a^ e r^ 14b^ são ambos -h ou um é -h e o outro é -oh, och~ 3~ ou -och~ 2~ch~ 3~ ou r^ 14a^ e r^ 14b^ em conjunto formam um grupo ceto; e r^ 15^ e r^ 18^ são independentemente escolhidos de -h ou -oh ou r^ 5^ e r^ 3^ são ambos ceto e o anel a é p-benzoquinona. nos materiais de partida modificados, o grupo 21-ciano pode ser substituído por outros grupos introduzidos usando reagentes nucleofílicos.
BRPI0010559A 1999-05-14 2000-05-15 processo hemissintético e compostos intermediários BRPI0010559B8 (pt)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GBGB9911345.8A GB9911345D0 (pt) 1999-05-14 1999-05-14
GBGB9918178.6A GB9918178D0 (en) 2000-05-15 1999-08-02 Synthetic methods
GBGB9923632.5A GB9923632D0 (en) 1999-10-06 1999-10-06 Hemisynthetic process towards ecteinascidin and phtalscidin compounds
GB0001063A GB0001063D0 (en) 2000-01-17 2000-01-17 Hemisynthetic process towards ecteinascidin and phtalascidin
PCT/GB2000/001852 WO2000069862A2 (en) 1999-05-14 2000-05-15 Hemisynthetic method and intermediates thereof

Publications (3)

Publication Number Publication Date
BR0010559A BR0010559A (pt) 2002-07-02
BRPI0010559B1 BRPI0010559B1 (pt) 2016-08-30
BRPI0010559B8 true BRPI0010559B8 (pt) 2021-05-25

Family

ID=42632476

Family Applications (3)

Application Number Title Priority Date Filing Date
BRPI0010559A BRPI0010559B8 (pt) 1999-05-14 2000-05-15 processo hemissintético e compostos intermediários
BR0110801-8 BRPI0110801B8 (pt) 1999-05-14 2001-05-15 análogos antitumorais de et-743, composição farmacêutica compreendendo os mesmos e uso dos referidos análogos
BR0110443-8 BRPI0110443B8 (pt) 1999-05-14 2001-05-15 etapas processuais na produção de um composto de ecteinascidina

Family Applications After (2)

Application Number Title Priority Date Filing Date
BR0110801-8 BRPI0110801B8 (pt) 1999-05-14 2001-05-15 análogos antitumorais de et-743, composição farmacêutica compreendendo os mesmos e uso dos referidos análogos
BR0110443-8 BRPI0110443B8 (pt) 1999-05-14 2001-05-15 etapas processuais na produção de um composto de ecteinascidina

Country Status (29)

Country Link
US (3) US7241892B1 (pt)
EP (1) EP1185536B1 (pt)
JP (1) JP4445136B2 (pt)
KR (1) KR100834601B1 (pt)
CN (3) CN1229382C (pt)
AR (1) AR035842A1 (pt)
AT (1) ATE283273T1 (pt)
AU (2) AU775580B2 (pt)
BG (1) BG65896B1 (pt)
BR (3) BRPI0010559B8 (pt)
CA (2) CA2372058C (pt)
CY (1) CY1108095T1 (pt)
CZ (3) CZ303536B6 (pt)
DE (1) DE60016209T2 (pt)
DK (1) DK1185536T3 (pt)
ES (2) ES2233367T3 (pt)
HU (1) HU230646B1 (pt)
MX (1) MXPA01011631A (pt)
MY (1) MY130271A (pt)
NO (2) NO322016B1 (pt)
NZ (1) NZ515424A (pt)
PL (1) PL226890B1 (pt)
PT (1) PT1185536E (pt)
RU (1) RU2237063C9 (pt)
SI (2) SI1185536T1 (pt)
SK (2) SK287835B6 (pt)
TR (1) TR200103273T2 (pt)
UA (1) UA75333C2 (pt)
WO (3) WO2000069862A2 (pt)

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CA2331593C (en) 1998-05-11 2008-08-05 Pharma Mar, S.A. Metabolites of ecteinascidin 743
MY164077A (en) 1999-05-13 2017-11-30 Pharma Mar Sa Compositions and uses of et743 for treating cancer
AR035842A1 (es) 1999-05-14 2004-07-21 Pharma Mar Sa Metodo de hemisintesis para la formacion de compuestos intermediarios y derivados y de estructuras relacionadas con la ecteinascidina y de tetrahidroisoquinolinfenoles y compuestos intermediarios de aplicacion en dicho metodo
US7919493B2 (en) 2000-04-12 2011-04-05 Pharma Mar, S.A. Anititumoral ecteinascidin derivatives
WO2001077115A1 (en) 2000-04-12 2001-10-18 Pharma Mar, S.A. Antitumoral ecteinascidin derivatives
MXPA02011319A (es) 2000-05-15 2003-06-06 Pharma Mar Sa Analogos antitumorales de ecteinascidina 743.
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US7420051B2 (en) 2000-05-15 2008-09-02 Pharma Mar, S.A. Synthetic process for the manufacture of an ecteinaschidin compound
CA2447553A1 (en) 2000-11-03 2002-05-23 President And Fellows Of Harvard College Saframycins, analogues and uses thereof
BR0115162A (pt) * 2000-11-06 2003-10-21 Pharma Mar Sa Tratamentos antitumorais eficazes
GB0117402D0 (en) * 2001-07-17 2001-09-05 Pharma Mar Sa New antitumoral derivatives of et-743
GB0119243D0 (en) 2001-08-07 2001-10-03 Pharma Mar Sa Antitumoral analogs of ET-743
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GB0312407D0 (en) * 2003-05-29 2003-07-02 Pharma Mar Sau Treatment
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HRP20080598T3 (en) 2003-11-13 2009-01-31 Pharma Mar Combination of et-743 with 5-fluorouracil pro-drugs for the treatment of cancer
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AU2005288696A1 (en) * 2004-09-28 2006-04-06 Pharma Mar S.A., Sociedad Unipersonal Ecteinascidin compounds as anti -inflammatory agents
EP1827500B1 (en) * 2004-10-26 2009-05-06 Pharma Mar S.A., Sociedad Unipersonal Pegylated liposomal doxorubicin in combination with ecteinescidin 743
ATE368461T1 (de) 2004-10-29 2007-08-15 Pharma Mar Sa Zusammensetzungen enthaltend ecteinascidin und einen disaccharide
GB0522082D0 (en) 2005-10-31 2005-12-07 Pharma Mar Sa Formulations
KR100712667B1 (ko) 2006-04-11 2007-05-02 재단법인서울대학교산학협력재단 신규한 디아자 헤테로고리 유도체 및 그의 고체상 제조방법
GB0708691D0 (en) * 2007-05-04 2007-06-13 Pharma Mar Sa Anticancer treatments a
US20090076017A1 (en) * 2007-09-15 2009-03-19 Protia, Llc Deuterium-enriched trabectedin
US20100267732A1 (en) * 2007-10-19 2010-10-21 Pharma Mar, S.A. Prognostic Molecular Markers for ET-743 Treatment
JP2011520921A (ja) * 2008-05-16 2011-07-21 ファルマ・マール・ソシエダード・アノニマ 抗腫瘍アルカロイドとの併用療法
NZ589270A (en) * 2008-05-16 2011-12-22 Pharma Mar Sa Multiple myeloma treatments
WO2011048210A1 (en) 2009-10-22 2011-04-28 Pharma Mar, S.A. PDGFR-α AS RESPONSE MARKER FOR PM00104 TREATMENT
CN103038240A (zh) * 2010-05-25 2013-04-10 法马马有限公司 制备海鞘素化合物的合成方法
RS54648B1 (sr) 2010-11-12 2016-08-31 Pharma Mar S.A. Kombinovana terapija sa antitumorskim alkaloidom
KR102491180B1 (ko) 2017-04-27 2023-01-20 파르마 마르 에스.에이. 항종양 화합물
CN107739387B (zh) * 2017-10-16 2020-01-03 上海皓元生物医药科技有限公司 一种制备曲贝替定的关键中间体化合物的方法
CN109912629B (zh) * 2017-12-13 2021-12-24 浙江中科创越药业有限公司 天然产物Trabectedin的制备
TWI824043B (zh) 2018-10-25 2023-12-01 西班牙商瑪製藥股份有限公司 藥物抗體共軛物
CN111518110B (zh) * 2019-02-01 2023-11-03 博瑞生物医药（苏州）股份有限公司 一种海鞘素化合物及其中间体的制备方法
CN111620792B (zh) * 2019-02-28 2023-01-03 兰州大学 一种n,n-二取代氰基甲酰胺的合成方法
PE20252386A1 (es) 2019-11-21 2025-10-10 Pharma Mar Sa Metodo de tratamiento del cancer de pulmon de celulas pequenas con formulaciones de lurbinectedina
CN116217584A (zh) * 2021-12-06 2023-06-06 南通诺泰生物医药技术有限公司 Et743及其中间体的光催化合成方法
CN117659032A (zh) * 2022-08-29 2024-03-08 南通诺泰生物医药技术有限公司 海鞘素类衍生物的中间体及其的合成方法
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Also Published As

Publication number Publication date
PT1185536E (pt) 2005-04-29
CA2372058C (en) 2010-10-26
BG65896B1 (bg) 2010-04-30
SI1287004T1 (sl) 2005-12-31
NO20015547D0 (no) 2001-11-13
PL226890B1 (pl) 2017-09-29
NO322016B1 (no) 2006-08-07
US20080045713A1 (en) 2008-02-21
HUP0201188A2 (en) 2002-07-29
CZ20023751A3 (en) 2004-05-12
BRPI0110801B1 (pt) 2018-02-27
BRPI0110443B1 (pt) 2018-06-26
BRPI0110801B8 (pt) 2021-05-25
CA2372058A1 (en) 2000-11-23
AU4597300A (en) 2000-12-05
CA2406095C (en) 2010-02-16
NO328301B1 (no) 2010-01-25
AR035842A1 (es) 2004-07-21
BR0010559A (pt) 2002-07-02
CN100475822C (zh) 2009-04-08
DE60016209T2 (de) 2005-12-15
JP4445136B2 (ja) 2010-04-07
BRPI0110443B8 (pt) 2021-05-25
US20040002602A1 (en) 2004-01-01
CZ304966B6 (cs) 2015-02-18
US7524956B2 (en) 2009-04-28
BR0110801A (pt) 2003-02-11
BG107301A (bg) 2003-07-31
SK16502001A3 (sk) 2002-06-04
CA2406095A1 (en) 2001-11-22
EP1185536B1 (en) 2004-11-24
SK287835B6 (sk) 2011-12-05
WO2000069862A3 (en) 2001-03-22
CZ20014102A3 (cs) 2002-06-12
KR20020021636A (ko) 2002-03-21
JP2002544280A (ja) 2002-12-24
CN1229382C (zh) 2005-11-30
ATE283273T1 (de) 2004-12-15
WO2001087895A1 (en) 2001-11-22
BRPI0010559B1 (pt) 2016-08-30
HU230646B1 (hu) 2017-05-29
NZ515424A (en) 2004-06-25
CZ303536B6 (cs) 2012-11-21
ES2233367T3 (es) 2005-06-16
EP1185536A2 (en) 2002-03-13
SI1185536T1 (en) 2005-06-30
MXPA01011631A (es) 2002-07-30
NO20025186L (no) 2003-01-14
ES2231486T3 (es) 2005-05-16
WO2000069862A2 (en) 2000-11-23
MY130271A (en) 2007-06-29
WO2001087894A1 (en) 2001-11-22
SK287879B6 (sk) 2012-02-03
UA75333C2 (uk) 2006-04-17
TR200103273T2 (tr) 2002-04-22
AU5649601A (en) 2001-11-26
CN1211386C (zh) 2005-07-20
CZ20023746A3 (cs) 2003-04-16
CY1108095T1 (el) 2014-02-12
BR0110443A (pt) 2003-04-08
CN1441805A (zh) 2003-09-10
NO20025186D0 (no) 2002-10-29
DK1185536T3 (da) 2005-04-04
AU775580B2 (en) 2004-08-05
CN1440414A (zh) 2003-09-03
NO20015547L (no) 2002-01-14
SK15272002A3 (sk) 2003-06-03
RU2237063C9 (ru) 2008-10-10
US7241892B1 (en) 2007-07-10
RU2237063C2 (ru) 2004-09-27
HK1047432A1 (en) 2003-02-21
KR100834601B1 (ko) 2008-06-02
PL353002A1 (en) 2003-09-22
DE60016209D1 (de) 2004-12-30
CN1360588A (zh) 2002-07-24
CZ304973B6 (cs) 2015-02-25

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