ES2205663T3 - Uso antineoplasico de delta 6,7-taxoles y composiciones farmaceuticas que los contienen. - Google Patents

Uso antineoplasico de delta 6,7-taxoles y composiciones farmaceuticas que los contienen.

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Publication number
ES2205663T3
ES2205663T3 ES99118033T ES99118033T ES2205663T3 ES 2205663 T3 ES2205663 T3 ES 2205663T3 ES 99118033 T ES99118033 T ES 99118033T ES 99118033 T ES99118033 T ES 99118033T ES 2205663 T3 ES2205663 T3 ES 2205663T3
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Prior art keywords
nhc
phenyl
substd
opt
alkyl
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Expired - Lifetime
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ES99118033T
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English (en)
Inventor
Robert C. Kelly
Roy A. Johnson
Harvey I. Skulnick
Eldon G. Nidy
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Pharmacia and Upjohn Co
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Pharmacia and Upjohn Co
Upjohn Co
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Priority claimed from PCT/US1993/011827 external-priority patent/WO1994013655A1/en
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D263/00Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/04Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D263/00Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/04Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D263/06Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by oxygen atoms, attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D305/00Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
    • C07D305/14Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D407/00Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02Silicon compounds
    • C07F7/08Compounds having one or more C—Si linkages
    • C07F7/18Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804Compounds having Si-O-C linkages
    • YGENERAL 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
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/55Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Epoxy Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Esta invención proporciona 7-desoxi-dl6,7-taxol y análogos de 7-desoxi-dl6,7-taxol de *fórmula *. Los compuestos se utilizan para los mismos cánceres para los que se ha mostrado activo el taxol, incluyendo el cáncer de ovarios, cáncer de pecho y melanoma maligno en humanos, así como cáncer de pulmón, cáncer gástrico, cáncer de colon, cáncer de cabeza y cuello y leucemia.

Description

Uso antineoplásico de \delta 6,7-taxoles y composiciones farmacéuticas que los contienen.
Campo de la invención
Esta invención se refiere a un procedimiento de preparación de 10-desacetiltaxol, taxótero y análogos de éstos.
Antecedentes de la invención
El taxol y el taxótero son potentes agentes anticancerosos.
El documento US-A-5248796 se refiere a derivados de 10-desacetoxi-11,12-dihidrotaxol-10,12(18)-dieno y a la preparación de 10-desacetoxitaxol.
Samaranayake y col., J. Org. Chem., 1991, 56, 5114, describe un procedimiento para la extracción del grupo acilo de la posición 10 de las estructuras del taxol y de la baccatina, usando bromuro de cinc en metanol. Este procedimiento da una gran cantidad de otros productos además del producto deseado de desacilación.
Resumen de la invención
La presente invención es un procedimiento de desacetilación que usa hidracina, que se define en las reivindicaciones.
Descripción de la invención
En una realización de la invención, la reacción del taxol y de análogos del taxol 1
1
en la que R_{15} es acetilo, baccatina III o análogos de baccatina III 2
2
en la que R_{6} es acetilo, con hidracina comprende un procedimiento particularmente ventajoso para la preparación de 10-desacetiltaxol, análogos de 10-desacetiltaxol (1, R_{15}=H), 10-desacetilbaccatina III, y análogos de 10-desacetilbaccatina (2, R_{6}=H). La reacción con hidracina da casi exclusivamente el producto deseado de desacilación. La reacción puede ser realizada a temperatura ambiente en un disolvente orgánico y normalmente requiere tan poco tiempo como 15 minutos o tanto como 24 horas, dependiendo del sustrato. El disolvente preferente para la reacción es etanol al 95% y la hidracina al 98% es la forma preferida de reactivo.
Los siguientes ejemplos ilustran la invención.
Ejemplo 1 Taxótero
Se agitan 25 mg (0,029 mM) de 10-acetiltaxótero a temperatura ambiente bajo atmósfera de nitrógeno en 1,0 mL de etanol al 95%. Se añaden 2 gotas de hidracina anhidra y se dejan reaccionar durante 1,5 horas, hasta que la TLC muestra que la reacción está completa en su mayor parte. La reacción se reparte entre agua y cloruro de metileno. La fase acuosa se extrae de nuevo con cloruro de metileno. Las fases orgánicas se combinan, se secan sobre sulfato sódico y se evaporan a vacío.
El producto bruto se pasa por cromatografía sobre 3 g de gel de sílice, eluyendo con acetato de etilo-hexano 70-30. Se recogen fracciones de 1 ml, y se analizan por TLC. Las fracciones 14-28 contienen el producto y se combinan y se evaporan a vacío.
TLC: gel de sílice 60; EtAcO-hexano 70-30; Rf: 0,33.
RMN ^{1}H (CDCl_{3}, TMS) \delta 1,12 (s, 3H); 1,23 (s, 3H); 1,34 (s, 9H); 1,74 (s, 3H); 1,85 (s, 3H); 2,37 (s, 3H); 2,56 (m, 1H); 3,53 (s.ancho, 1H); 3,90 (d, 1H); 4,18 (d, 1H); 4,21 (m, 1H); 4,30 (d, 1H); 4,32 (s, 1H); 4,62 (s.ancho, 1H); 4,94 (d, 1H); 5,23 (s, 1H); 5,28 (s.ancho, 1H); 5,52 (d, 1H); 5,66 (d, 1H); 6,20 (t, 1H); 7,25-7,45 (m, 6H); 7,50 (t, 2H); 7,61 (t, 1H); 8,11 (d, 2H).
Ejemplo 2 10-Deacetiltaxol
Se agita una disolución de taxol (0,026 g, 0,030 mmol) e hidracina al 98% (0,035 g, 1,1 mmol) en etanol al 95% (1,0 mL) a temperatura ambiente durante 2 horas. La disolución se vierte en agua y éter, la mezcla se agita bien, y las fases se separan. La fase acuosa se extrae con más éter. Los extractos combinados de éter se secan sobre Na_{2}SO_{4}, se filtran y se concentran, para dar 0,021 g del compuesto del título; su espectro de RMN ^{1}H en CDCl_{3} es idéntico al espectro publicado para el 10-desacetiltaxol (Ringel, I.; Horwitz, S.B. J. Pharmacol. Exp. Ther., 1987, 242, 692) y es idéntico al espectro de una muestra auténtica.
Ejemplo 3 10-deacetilbaccatina III
Se prepara una disolución de baccatina III (0,024 g, 0,041 mmol) en etanol al 95% (1,0 mL) por calentamiento de la mezcla. La disolución se enfría a temperatura ambiente, se añade hidracina al 98% (0,035 g, 1,1 mmol) y la disolución se agita a temperatura ambiente durante 24 horas. La disolución se vierte en agua/éter, se agita bien, y las fases se separan. La fase etérea se lava con agua, se seca (Na_{2}SO_{4}), se filtra y se concentra, para dar 0,010 g del compuesto del título; su espectro de RMN ^{1}H en CDCl_{3} (ligeramente soluble) es idéntico al de una muestra auténtica de 10-deacetilbaccatina III.

Claims (2)

1. Un procedimiento para la preparación de un compuesto de fórmula:
3
en la que R_{1} se selecciona del grupo constituido por
-CH_{3},
-C_{6}H_{5} o fenilo sustituido por uno, 2 ó 3 alquilo C_{1}-C_{4}, alcoxi C_{1}-C_{3}, halo, alquiltio C_{1}-C_{3}, trifluorometilo, dialquilamino C_{2}-C_{6}, hidroxi o nitro,
-2-furilo, 2-tienilo, 1-naftilo, 2-naftilo o 3,4-metilendioxifenilo;
R_{2} se selecciona del grupo constituido por -H, NHC(O)H, -NHC(O)alquilo(C_{1}-C_{10}), -NHC(O)fenilo, -NHC(O)fenilo sustituido por uno, 2 ó 3 alquilo C_{1}-C_{4}, alcoxi C_{1}-C_{3}, halo, alquiltio C_{1}-C_{3}, trifluorometilo, dialquilamino C_{2}-C_{6}, hidroxi o nitro, -NHC(O)C(CH_{3})=CHCH_{3}, -NHC(O)OC(CH_{3})_{3}, -NHC(O)OCH_{2}fenilo, -NH2, -NHSO_{2}-4-metilfenilo, -NHC(O)(CH_{2})_{3}COOH, -NHC(O)-4-(SO_{3}H)fenilo, -OH, -NHC(O)-1-adamantilo, -NHC(O)O-3-tetrahidrofuranilo, -NHC(O)O-4-tetrahidropiranilo, -NHC(O)CH_{2}C(CH_{3})_{3}, -NHC(O)C(CH_{3})_{3}, -NHC(O)Oalquilo(C_{1}-C_{10}), -NHC(O)NHalquilo(C_{1}-C_{10}), -NHC(O)NHPh, -NHC(O)NHPh sustituido por uno, 2 ó 3 alquilo C_{1}-C_{4}, alcoxi C_{1}-C_{3}, halo, alquiltio C_{1}-C_{3}, trifluorometilo, dialquilamino C_{2}-C_{6} o nitro, -NHC(O)cicloalquilo(C_{3}-C_{8}), -NHC(O)C(CH_{2}
\hbox{CH _{3} ) _{2} }
CH_{3}, -NHC(O)C(CH_{3})_{2}CH_{2}Cl, -NHC(O)C(CH_{3})_{2}CH_{2}CH_{3}, ftalimido, -NHC(O)-1-fenil-1-ciclopentilo, -NHC(O)-1-metil-1-ciclohexilo, -NHC(S)NHC(CH_{3})_{3} o -NHC(O)NHC(CH_{3})_{3};
R_{3} se selecciona del grupo constituido por -H, NHC(O)fenilo o -NHC(O)OC(CH_{3})_{3}, con la condición general de que uno de R_{2} o R_{3} sea -H, pero que R_{2} y R_{3} no sean ambos -H;
Bz es -C(O)fenilo; y
Ac es C(O)CH_{3};
que comprende hacer reaccionar de un compuesto de fórmula:
4
en la que R_{1}, R_{2}, R_{3}, Bz y Ac son como se ha definido anteriormente;
con hidracina.
2. Un procedimiento de preparación de un compuesto de fórmula:
5
en la que Bz es C(O)fenilo y Ac es C(O)CH_{3};
que comprende hacer reaccionar de un compuesto de fórmula:
6
con hidracina.
ES99118033T 1993-06-11 1994-06-03 Uso antineoplasico de delta 6,7-taxoles y composiciones farmaceuticas que los contienen. Expired - Lifetime ES2205663T3 (es)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US7633793A 1993-06-11 1993-06-11
US76337 1993-06-11
US12297493A 1993-09-17 1993-09-17
US122974 1993-09-17
WOPCT/US93/11827 1993-12-13
PCT/US1993/011827 WO1994013655A1 (en) 1992-12-15 1993-12-13 7-HALO- AND 7β,8β-METHANO-TAXOLS, ANTINEOPLASTIC USE AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Publications (1)

Publication Number Publication Date
ES2205663T3 true ES2205663T3 (es) 2004-05-01

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ES94920688T Expired - Lifetime ES2145829T3 (es) 1993-06-11 1994-06-03 Uso antineoplasico de delta 6,7-taxoles y composiciones farmaceuticas que los contienen.
ES99118034T Expired - Lifetime ES2219968T3 (es) 1993-06-11 1994-06-03 Uso antineoplasico de delta 6,7-taxoles y composiciones farmaceuticas que los contienen.
ES99118033T Expired - Lifetime ES2205663T3 (es) 1993-06-11 1994-06-03 Uso antineoplasico de delta 6,7-taxoles y composiciones farmaceuticas que los contienen.

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ES94920688T Expired - Lifetime ES2145829T3 (es) 1993-06-11 1994-06-03 Uso antineoplasico de delta 6,7-taxoles y composiciones farmaceuticas que los contienen.
ES99118034T Expired - Lifetime ES2219968T3 (es) 1993-06-11 1994-06-03 Uso antineoplasico de delta 6,7-taxoles y composiciones farmaceuticas que los contienen.

Country Status (18)

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US (2) US5965739A (es)
EP (3) EP0982302B1 (es)
JP (1) JPH09511212A (es)
AT (3) ATE249448T1 (es)
AU (1) AU7138894A (es)
CA (1) CA2161328A1 (es)
DE (3) DE69424166T2 (es)
DK (3) DK0982302T3 (es)
ES (3) ES2145829T3 (es)
GR (1) GR3033836T3 (es)
IL (1) IL109957A (es)
LV (2) LV12692B (es)
NZ (2) NZ268475A (es)
PT (3) PT982302E (es)
SI (2) SI0703909T1 (es)
TW (1) TW401407B (es)
WO (1) WO1994029288A1 (es)
ZA (1) ZA944034B (es)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5998656A (en) * 1991-09-23 1999-12-07 Florida State University C10 tricyclic taxanes
FR2696460B1 (fr) * 1992-10-05 1994-11-25 Rhone Poulenc Rorer Sa Procédé de préparation de dérivés du taxane.
FR2697522B1 (fr) * 1992-10-30 1994-11-25 Rhone Poulenc Rorer Sa Procédé de préparation de dérivés du taxane.
US5380751A (en) * 1992-12-04 1995-01-10 Bristol-Myers Squibb Company 6,7-modified paclitaxels
CA2109861C (en) * 1992-12-04 1999-03-16 Shu-Hui Chen 6,7-modified paclitaxels
FR2721025B1 (fr) * 1994-06-09 1996-07-12 Rhone Poulenc Rorer Sa Nouveaux taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent.
FR2721026B1 (fr) * 1994-06-09 1996-07-12 Rhone Poulenc Rorer Sa Nouveaux taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent.
IT1275936B1 (it) * 1995-03-17 1997-10-24 Indena Spa Derivati della 10-deacetilbaccatina iii e della 10-deacetil-14b- idrossibaccatina iii loro metodo di preparazione e formulazioni
CA2170661A1 (en) * 1995-03-22 1996-09-23 John K. Thottathil Novel methods for the preparation of taxanes using oaxzolidine intermediates
US5780653A (en) * 1995-06-07 1998-07-14 Vivorx Pharmaceuticals, Inc. Nitrophenyl, 10-deacetylated substituted taxol derivatives as dual functional cytotoxic/radiosensitizers
EP1114815B1 (en) * 1996-05-08 2004-09-29 PHARMACIA & UPJOHN COMPANY Process to prepare taxol
PL329637A1 (en) 1996-05-08 1999-04-12 Upjohn Co Taxol obtained method
ATE302599T1 (de) 1996-05-24 2005-09-15 Angiotech Pharm Inc Zubereitungen und verfahren zur behandlung oder prävention von krankheiten der körperpassagewege
US5977386A (en) * 1996-12-24 1999-11-02 Bristol-Myers Squibb Company 6-thio-substituted paclitaxels
US5912264A (en) * 1997-03-03 1999-06-15 Bristol-Myers Squibb Company 6-halo-or nitrate-substituted paclitaxels
US5837283A (en) * 1997-03-12 1998-11-17 The Regents Of The University Of California Cationic lipid compositions targeting angiogenic endothelial cells
US7112338B2 (en) * 1997-03-12 2006-09-26 The Regents Of The University Of California Cationic liposome delivery of taxanes to angiogenic blood vessels
US6017935A (en) * 1997-04-24 2000-01-25 Bristol-Myers Squibb Company 7-sulfur substituted paclitaxels
US6150537A (en) 1997-12-12 2000-11-21 Emory University Methods for the esterification of alcohols and compounds useful therefor as potential anticancer agents
US6235776B1 (en) 1998-11-12 2001-05-22 Cell Pathways, Inc. Method for treating a patient with neoplasia by treatment with a paclitaxel derivative
US6235782B1 (en) 1998-11-12 2001-05-22 Rifat Pamukcu Method for treating a patient with neoplasia by treatment with a platinum coordination complex
BR0013866A (pt) * 1999-09-09 2002-05-14 Univ California Distribuição de lipossomas catiÈnicos de taxanos aos vasos sanguineos angiogênicos
EP2289549A3 (en) 1999-10-01 2011-06-15 Immunogen, Inc. Immunoconjugates for treating cancer
US6414015B1 (en) * 2000-01-28 2002-07-02 Utah State University Laulimalide microtubule stabilizing agents
US6649632B2 (en) * 2000-02-02 2003-11-18 Fsu Research Foundation, Inc. C10 ester substituted taxanes
IL145640A (en) * 2000-02-02 2007-02-11 Univ Florida State Res Found Texans are converted to C10 in myamloxy as anti-cancer agents
JP2003521514A (ja) 2000-02-02 2003-07-15 フロリダ・ステイト・ユニバーシティ・リサーチ・ファウンデイション・インコーポレイテッド 抗腫瘍剤としてのc10ヘテロ置換アセテートタキサン
JP2003522171A (ja) 2000-02-02 2003-07-22 フロリダ・ステイト・ユニバーシティ・リサーチ・ファウンデイション・インコーポレイテッド 抗腫瘍剤としてのc10カーボネート置換タキサン
CO5280224A1 (es) 2000-02-02 2003-05-30 Univ Florida State Res Found Taxanos sustituidos con ester en c7, utiles como agentes antitumorales y composiciones farmaceuticas que los contienen
RU2265019C2 (ru) 2000-02-02 2005-11-27 Флорида Стейт Юниверсити Рисерч Фаундейшн, Инк. Таксаны, фармацевтические композиции, способы ингибирования
US6362217B2 (en) 2000-03-17 2002-03-26 Bristol-Myers Squibb Company Taxane anticancer agents
CA2410632A1 (en) 2000-06-22 2001-12-27 David S. Garvey Nitrosated and nitrosylated taxanes, compositions and methods of use
HUP0302599A3 (en) 2000-09-22 2005-05-30 Bristol Myers Squibb Co Method for reducing toxicity of combined chemotherapic compositions
US6726923B2 (en) 2001-01-16 2004-04-27 Vascular Therapies, Llc Apparatus and methods for preventing or treating failure of hemodialysis vascular access and other vascular grafts
DK1383754T3 (da) * 2001-03-23 2011-04-04 Scinopharm Taiwan Ltd Fremgangsmåde til syntetisering af taxanderivater
CA2354478A1 (en) * 2001-07-31 2003-01-31 Florida State University Research Foundation, Inc. C10 carbonate substituted taxanes
ATE431343T1 (de) * 2002-10-09 2009-05-15 Chatham Biotec Ltd Thio-analoga von paclitaxel und deren vorprodukte
US7064980B2 (en) * 2003-09-17 2006-06-20 Sandisk Corporation Non-volatile memory and method with bit line coupled compensation
SV2006002010A (es) * 2004-02-13 2006-08-23 Univ Florida State Res Found Taxanos sustituidos con esteres de ciclopentilo en c10
JP2007527432A (ja) 2004-03-05 2007-09-27 フロリダ・ステイト・ユニバーシティ・リサーチ・ファウンデイション・インコーポレイテッド C7ラクチルオキシ置換タキサン
EP1848423A4 (en) * 2005-02-14 2008-12-31 Univ Florida State Res Found C10 CYCLOPROPYL ESTER SUBSTITUTED TAXAN COMPOSITIONS
US20100069643A1 (en) * 2005-12-21 2010-03-18 Mcchesney James D Convergent Process for the Synthesis of Taxane Derivatives
ITMI20062479A1 (it) * 2006-12-21 2008-06-22 Indena Spa Processo per la preparazione di secotassani
ES2389518T3 (es) 2008-01-18 2012-10-26 Indena S.P.A. Formas sólidas de ortataxel
US8242166B2 (en) * 2008-03-31 2012-08-14 Florida State University Research Foundation, Inc. C(10) ethyl ester and C(10) cyclopropyl ester substituted taxanes
WO2011134067A1 (en) * 2010-04-29 2011-11-03 6570763 Canada Inc. Novel amino acid molecule and uses thereof
CN101863862B (zh) * 2010-06-18 2012-01-11 云南汉德生物技术有限公司 一种工业半合成紫杉醇的方法
CN103980232A (zh) * 2014-06-05 2014-08-13 北京诺普德医药科技有限公司 10-乙酰基多西紫杉醇及其用途
CN111138386A (zh) * 2019-12-30 2020-05-12 重庆市碚圣医药科技股份有限公司 一种多西他赛的半合成方法
CN115260130A (zh) * 2022-07-07 2022-11-01 上海卓鼎生物技术有限公司 一种10-脱乙酰基紫杉醇的制备方法
CN116462643A (zh) * 2023-03-29 2023-07-21 无锡贝塔医药科技有限公司 一种氘或氚标记的多西他赛的合成方法

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2601676B1 (fr) * 1986-07-17 1988-09-23 Rhone Poulenc Sante Procede de preparation du taxol et du desacetyl-10 taxol
FR2601675B1 (fr) * 1986-07-17 1988-09-23 Rhone Poulenc Sante Derives du taxol, leur preparation et les compositions pharmaceutiques qui les contiennent
US4876399A (en) * 1987-11-02 1989-10-24 Research Corporation Technologies, Inc. Taxols, their preparation and intermediates thereof
US5157049A (en) * 1988-03-07 1992-10-20 The United States Of America As Represented By The Department Of Health & Human Services Method of treating cancers sensitive to treatment with water soluble derivatives of taxol
US4942184A (en) * 1988-03-07 1990-07-17 The United States Of America As Represented By The Department Of Health And Human Services Water soluble, antineoplastic derivatives of taxol
FR2629818B1 (fr) * 1988-04-06 1990-11-16 Centre Nat Rech Scient Procede de preparation du taxol
FR2629819B1 (fr) * 1988-04-06 1990-11-16 Rhone Poulenc Sante Procede de preparation de derives de la baccatine iii et de la desacetyl-10 baccatine iii
EP0366841A1 (en) * 1988-11-03 1990-05-09 Dresser-Rand Company A crosshead and crosshead pin coupling arrangement
US4960790A (en) * 1989-03-09 1990-10-02 University Of Kansas Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
US5175315A (en) * 1989-05-31 1992-12-29 Florida State University Method for preparation of taxol using β-lactam
CA2023645C (fr) * 1989-08-23 2002-03-26 Jean-Noel Denis Procede pour la preparation enantioselective de derives de la phenylisoserine
US5136060A (en) * 1989-11-14 1992-08-04 Florida State University Method for preparation of taxol using an oxazinone
US5015744A (en) * 1989-11-14 1991-05-14 Florida State University Method for preparation of taxol using an oxazinone
FR2658513B1 (fr) * 1990-02-21 1994-02-04 Rhone Poulenc Sante Procede de preparation de l'acide cis-beta-phenylglycidique-(2r,3r).
FR2658510B1 (fr) * 1990-02-21 1992-04-30 Rhone Poulenc Sante Nouveau derive de la beta-phenylisoserine, sa preparation et son emploi.
FR2662440B1 (fr) * 1990-05-22 1992-07-31 Rhone Poulenc Sante Procede de preparation stereoselective de derives de la phenylisoserine.
FR2662441B1 (fr) * 1990-05-22 1992-10-23 Rhone Poulenc Sante Procede de preparation enantioselective de derives de la phenylisoserine.
US5059699A (en) * 1990-08-28 1991-10-22 Virginia Tech Intellectual Properties, Inc. Water soluble derivatives of taxol
MX9102128A (es) * 1990-11-23 1992-07-08 Rhone Poulenc Rorer Sa Derivados de taxano,procedimiento para su preparacion y composicion farmaceutica que los contiene
FR2679230B1 (fr) * 1991-07-16 1993-11-19 Rhone Poulenc Rorer Sa Nouveaux derives d'analogues du taxol, leur preparation et les compositions qui les contiennent.
US5250683A (en) * 1991-09-23 1993-10-05 Florida State University Certain substituted taxanes and pharmaceutical compositions containing them
US5227400A (en) * 1991-09-23 1993-07-13 Florida State University Furyl and thienyl substituted taxanes and pharmaceutical compositions containing them
FR2687151B1 (fr) * 1992-02-07 1994-03-25 Rhone Poulenc Rorer Sa Nouveaux derives de la baccatine iii et de la desacetyl-10 baccatine iii, leur preparation et les compositions pharmaceutiques qui les contiennent.
US5248796A (en) * 1992-06-18 1993-09-28 Bristol-Myers Squibb Company Taxol derivatives
US5294637A (en) * 1992-07-01 1994-03-15 Bristol-Myers Squibb Company Fluoro taxols
US5254580A (en) * 1993-01-19 1993-10-19 Bristol-Myers Squibb Company 7,8-cyclopropataxanes
ATE136460T1 (de) * 1992-07-01 1996-04-15 Bristol Myers Squibb Co Fluor-taxole mit antitumor-wirkung
FR2696458B1 (fr) * 1992-10-05 1994-11-10 Rhone Poulenc Rorer Sa Procédé de préparation de dérivés du taxane.
FR2696459B1 (fr) * 1992-10-05 1994-11-25 Rhone Poulenc Rorer Sa Procédé de préparation de dérivés du taxane.
FR2696460B1 (fr) * 1992-10-05 1994-11-25 Rhone Poulenc Rorer Sa Procédé de préparation de dérivés du taxane.
FR2696464B1 (fr) * 1992-10-05 1994-11-10 Rhone Poulenc Rorer Sa Nouveau procédé d'estérification de la baccatine III et de la désacétyl-10 baccatine III.
FR2697522B1 (fr) * 1992-10-30 1994-11-25 Rhone Poulenc Rorer Sa Procédé de préparation de dérivés du taxane.
US5380751A (en) * 1992-12-04 1995-01-10 Bristol-Myers Squibb Company 6,7-modified paclitaxels
CA2109861C (en) * 1992-12-04 1999-03-16 Shu-Hui Chen 6,7-modified paclitaxels
FR2698871B1 (fr) * 1992-12-09 1995-02-24 Rhone Poulenc Rorer Sa Nouveau taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent.

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AU7138894A (en) 1995-01-03
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US5965739A (en) 1999-10-12
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ATE264316T1 (de) 2004-04-15
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