ES2331506T3 - Derivados de 6-alquenil-, 6-alquinil-, 6-epoxi-epotilona, procedimiento para su produccion, y su uso en preparaciones farmaceuticas. - Google Patents

Derivados de 6-alquenil-, 6-alquinil-, 6-epoxi-epotilona, procedimiento para su produccion, y su uso en preparaciones farmaceuticas. Download PDF

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ES2331506T3
ES2331506T3 ES00922826T ES00922826T ES2331506T3 ES 2331506 T3 ES2331506 T3 ES 2331506T3 ES 00922826 T ES00922826 T ES 00922826T ES 00922826 T ES00922826 T ES 00922826T ES 2331506 T3 ES2331506 T3 ES 2331506T3
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alkyl
substituted
acyl
optionally
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Ulrich Klar
Wolfgang Schwede
Werner Skuballa
Bernd Buchmann
Jens Hoffmann
Rosemarie Lichtner
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Bayer Pharma AG
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Bayer Schering Pharma AG
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Priority claimed from DE19921086A external-priority patent/DE19921086A1/de
Priority claimed from DE19954228A external-priority patent/DE19954228A1/de
Priority claimed from DE10015836A external-priority patent/DE10015836A1/de
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/02—Heterocyclic 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
    • C07D405/06—Heterocyclic 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 carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/02—Heterocyclic 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
    • C07D405/04—Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/14—Heterocyclic 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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/04—Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/06—Heterocyclic 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 carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Un compuesto de epotilona de fórmula I, **(Ver fórmula)** en la que R1a, R1b son iguales o diferentes, y significan hidrógeno; alquilo C1-C10, que puede estar opcionalmente perfluorado o sustituido con 1-5 átomos de halógeno, grupo hidroxi, grupos alcoxi C1-C4, o grupos arilo C6-C12 opcionalmente sustituido, que pueden estar sustituidos con 1-3 átomos de halógeno, arilo C6-C12, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, Oalquilo, CO2H, CO2-alquilo, -NH2, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi o aralquilo C7-C20, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, O-alquilo, CO2H, CO2-alquilo, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi, o tomados juntos un grupo -(CH2)m- con m = 1, 2, 3,4 ó 5, o un grupo -(CH2)-O-(CH2)-; R2a significa hidrógeno, alquilo C1-C10, que puede estar opcionalmente perfluorado o sustituido con 1-5 átomos de halógeno, grupos hidroxi, grupos alcoxi C1-C4, grupos arilo C6-C12 opcionalmente sustituido, que pueden estar sustituidos con 1-3 átomos de halógeno, arilo C6-C12 que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, Oalquilo, CO2H, CO2-alquilo, -NH2, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi, o aralquilo C7-C20, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, O-alquilo, CO2H, CO2-alquilo, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi; -(CH2)ra-CC-(CH2)paR26a; -(CH2)ra-C=C-(CH2)pa-R26a R2b significa -(CH2)rb-C(CH2)pb-R26b, -(CH2)rb-C=C-(CH2)pb-R26b, **(Ver fórmula)** n significa 0 a 5, ra, rb son iguales o diferentes, y significan 0 a 4, pa, pb son iguales o diferentes, y significan 0 a 3, R3a significa hidrógeno, o un alquilo C1-C10, que puede estar opcionalmente perfluorado o sustituido con 1-5 átomos de halógeno, grupos hidroxi, grupos alcoxi C1-C4, grupos arilo C6-C12 opcionalmente sustituido, que pueden estar sustituidos con 1-3 átomos de halógeno, arilo C6-C12, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, Oalquilo, CO2H, CO2-alquilo, -NH2, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi, o aralquilo C7-C20, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, O-alquilo, CO2H, CO2-alquilo, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi, R3b significa OH o OPG14, en el que PG14 es un grupo protector, R14 significa hidrógeno, OR14a o Hal, en el que R14a es hidrógeno, SO2-alquilo, SO2-arilo o SO2-aralquilo, R4 significa hidrógeno, alquilo C1-C10, que puede estar opcionalmente perfluorado o sustituido con 1-5 átomos de halógeno, grupos hidroxi, grupos alcoxi C1-C4, grupos arilo C6-C12 opcionalmente sustituido, que pueden estar sustituidos con 1-3 átomos de halógeno, arilo C6-C12, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, Oalquilo, CO2H, CO2-alquilo, -NH2, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi, o aralquilo C7-C20, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, O-alquilo, CO2H, CO2-alquilo, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi; Hal; OR25; o CN; R25 significa hidrógeno o un grupo protector PG5, R26a, R26b son iguales o diferentes, y significan hidrógeno; alquilo C1-C10, que puede estar opcionalmente perfluorado o sustituido con 1-5 átomos de halógeno, grupos hidroxi, grupos alcoxi C1-C4, grupos arilo C6-C12 opcionalmente sustituido, que pueden estar sustituidos con 1-3 átomos de halógeno, arilo C6-C12 que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, Oalquilo, CO2H, CO2-alquilo, -NH2, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi, o aralquilo C7-C20, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, O-alquilo, CO2H, CO2-alquilo, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi; acilo C1-C10, o, si pa o pb > 0, adicionalmente un grupo OR27, R27 significa hidrógeno o un grupo protector PG6, R5 significa hidrógeno, alquilo C1-C10, que puede estar opcionalmente perfluorado o sustituido con 1-5 átomos de halógeno, grupos hidroxi, grupos alcoxi C1-C4, grupos arilo C6-C12 opcionalmente sustituido, que pueden estar sustituidos con 1-3 átomos de halógeno, arilo C6-C12, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, Oalquilo, CO2H, CO2-alquilo, -NH2, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi aralquilo C7-C20, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, O-alquilo, CO2H, CO2-alquilo, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi; o (CH2)s-T, en el que s representa 1, 2, 3 ó 4, T representa OR22 o Hal, R22 representa hidrógeno o un grupo protector PG4, R6, R7 significan cada uno un átomo de hidrógeno, o tomados juntos un enlace adicional o un átomo de oxígeno, G significa un grupo X=CR8- o un radical arilo bi- o tricíclico, R8 significa hidrógeno; halógeno; CN; o un grupo alquilo C1-C20, que puede estar opcionalmente perfluorado o sustituido con 1-5 átomos de halógeno, grupos hidroxi, grupos alcoxi C1-C4, grupos arilo C6-C12 opcionalmente sustituido, que pueden estar sustituidos con 1-3 átomos de halógeno grupo arilo C6-C12, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, O-alquilo, CO2H, CO2-alquilo, -NH2, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi grupo aralquilo C7-C20, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, O-alquilo, CO2H, CO2-alquilo, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi, X significa un átomo de oxígeno, dos grupos alcoxi OR23, un grupo alquilen C2-C10-,!-dioxi, que puede ser de cadena lineal o ramificado, H/OR9 o un agrupamiento CR10R11, en el que R23 representa un radical alquilo C1-C20, R9 representa hidrógeno o un grupo protector PGx, R10, R11 son iguales o diferentes, y representan hidrógeno; un radical alquilo C1-C20, que puede estar opcionalmente perfluorado o sustituido con 1-5 átomos de halógeno, grupos hidroxi, grupos alcoxi C1-C4, grupos arilo C6-C12 opcionalmente sustituido, que pueden estar sustituidos con 1-3 átomos de halógeno radical arilo C6-C12, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, O-alquilo, CO2H, CO2-alquilo, -NH2, -NO2, -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi, o radical aralquilo C7-C20, que opcionalmente puede estar sustituido en uno o más lugares con grupos halógeno, OH, O-alquilo, CO2H, CO2-alquilo, -NO2; -N3, -CN, alquilo C1-C20, acilo C1-C20, acil C1-C20-oxi; o R10 y R11, junto con el átomo de carbono metilénico, representan conjuntamente un anillo carbocíclico de 5 a 7 miembros, D-E significa un grupo -CH2-CH2-, -O-CH2-, A-Y significa un grupo O-C(=O), O-CH2, CH2C(=O), NR29-C(=O), o NR29-SO2, R29 significa hidrógeno o alquilo C1-C10, Z significa un átomo de oxígeno o H/OR12, en el que R12 es hidrógeno o un grupo protector PG2, Hal significa halógeno.
ES00922826T 1999-04-30 2000-05-01 Derivados de 6-alquenil-, 6-alquinil-, 6-epoxi-epotilona, procedimiento para su produccion, y su uso en preparaciones farmaceuticas. Expired - Lifetime ES2331506T3 (es)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
DE19921086A DE19921086A1 (de) 1999-04-30 1999-04-30 6-Alkenyl- und 6-Alkinyl-Epothilon Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten
DE19921086 1999-04-30
DE19954228A DE19954228A1 (de) 1999-11-04 1999-11-04 6-Alkenyl-und 6-Alkinyl-Epothilon-Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten
DE19954228 1999-11-04
DE10015836 2000-03-27
DE10015836A DE10015836A1 (de) 2000-03-27 2000-03-27 6-Alkenyl- und 6-Alkinyl-Epothilon-Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten

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ES2331506T3 true ES2331506T3 (es) 2010-01-07

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EP (1) EP1173441B1 (es)
JP (2) JP4024003B2 (es)
KR (1) KR100721488B1 (es)
CN (1) CN100368415C (es)
AR (1) AR023792A1 (es)
AT (1) ATE440847T1 (es)
BG (1) BG65601B1 (es)
BR (1) BR0010190A (es)
CA (2) CA2651653C (es)
CY (1) CY1109768T1 (es)
CZ (1) CZ299653B6 (es)
DE (1) DE60042821D1 (es)
DK (1) DK1173441T3 (es)
EA (1) EA011502B1 (es)
EE (1) EE05292B1 (es)
ES (1) ES2331506T3 (es)
HK (1) HK1046681B (es)
HR (1) HRP20010892A2 (es)
HU (1) HUP0201010A3 (es)
IL (1) IL145938A0 (es)
ME (1) MEP13908A (es)
MX (1) MXPA01011039A (es)
NO (1) NO328149B1 (es)
NZ (1) NZ514989A (es)
PE (1) PE20010116A1 (es)
PL (1) PL210762B1 (es)
PT (1) PT1173441E (es)
RS (1) RS51023B (es)
SI (1) SI1173441T1 (es)
SK (1) SK286858B6 (es)
TW (2) TWI280962B (es)
WO (1) WO2000066589A1 (es)
ZA (1) ZA200109859B (es)

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