AR105193A1 - Síntesis de shishijimicina a y sus análogos - Google Patents

Síntesis de shishijimicina a y sus análogos

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Publication number
AR105193A1
AR105193A1 ARP160101973A ARP160101973A AR105193A1 AR 105193 A1 AR105193 A1 AR 105193A1 AR P160101973 A ARP160101973 A AR P160101973A AR P160101973 A ARP160101973 A AR P160101973A AR 105193 A1 AR105193 A1 AR 105193A1
Authority
AR
Argentina
Prior art keywords
substituted
hydrogen
alkyl
alkoxy
groups
Prior art date
Application number
ARP160101973A
Other languages
English (en)
Inventor
Wood James
Sohn Te
Ik - Lu Zhaoyong
Li Roufan
C Nicolaou Kyriacos
Original Assignee
Univ Rice William M
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
Application filed by Univ Rice William M filed Critical Univ Rice William M
Publication of AR105193A1 publication Critical patent/AR105193A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/20Carbocyclic rings
    • C07H15/24Condensed ring systems having three or more rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6807Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • 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
    • C07D405/06Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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 two hetero rings
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/10Spiro-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/20Carbocyclic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/20Carbocyclic rings
    • C07H15/203Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

En otro aspecto, la presente divulgación también provee métodos de preparación de dichos compuestos. En otro aspecto, la presente divulgación también provee composiciones farmacéuticas y métodos de uso de los compuestos. Adicionalmente, se proveen conjugados anticuerpo-fármaco que contienen los compuestos. Reivindicación 1: Un compuesto de la fórmula (1), donde: R¹ es -alcanodiilo C£₈-(S)ˣ-A³ o -alcanodiilo C£₈-(S)ˣ-A³ sustituido; donde: A³ es hidrógeno o alquilo C£₁₂, cicloalquilo C£₁₂, alquenilo C£₁₂, alquinilo C£₁₂, arilo C£₁₂, heteroarilo C£₁₂, aralquilo C£₁₂, acilo C£₁₂, o una versión sustituida de cualquiera de estos grupos; y x es 1, 2 ó 3; R² es hidroxilo, o alcoxilo C£₈, aciloxilo C£₈, o una versión sustituida de cualquiera de estos grupos; R³ es NHC(Y²)R¹⁶, donde: Y² es O, NH, o NOH; y R¹⁶ es alcoxilo C£₈, alqueniloxi C£₈, alquilamino C£₈, dialquilamino C£₈, o una versión sustituida de cualquiera de estos grupos; R⁴ y R⁵ se seleccionan en forma independiente entre si entre hidrógeno y halo; X¹ es O, S, o NH; A¹ es -alcanodiilo C£₁₂-C(O)-A² o -alcanodiilo C£₁₂-C(O)-A² sustituido, o un compuesto de fórmula (2) donde: X⁴ es -CH₂- o -O-; R⁸ es hidrógeno, alquilo C£₈, cicloalquilo C£₈, alquilo C£₈ sustituido, o cicloalquilo C£₈ sustituido; R⁹ es hidrógeno, halo, hidroxilo, mercapto, alquilo C£₈, alquilo C£₈, sustituido, alcoxilo C£₈, alcoxilo C£₈ sustituido, alquiltio C£₈, alquiltio C£₈ sustituido; R¹⁰ es hidroxilo, oxo, o R¹⁰ es tomado junto con R¹¹ y es -OCHA⁴O-; con la salvedad de que cuando R¹⁰ es oxo entonces R¹⁰ y el átomo de carbono al cual está unido están unidos mediante una unión doble, y cuando R¹⁰ es tomado junto con R¹¹ entonces R¹⁰ y el átomo de carbono al cual está unido están unidos mediante una unión simple; donde A⁴ es arilo C£₁₂ o arilo C£₁₂ sustituido, o un resto de fórmula (3) donde: X⁵ es O, S, o NR¹⁸; donde: R¹⁸ es hidrógeno, alquilo C£₈, alquilo C£₈ sustituido, acilo C£₈, o acilo C£₈ sustituido; Z¹ es CH o N; y R¹⁷ es hidrógeno, hidroxilo, amino, hidrazino, carboxilo, halo, o nitro; o alquilo C£₁₂, alcoxilo C£₁₂, o una versión sustituida de cualquiera de estos grupos; R¹¹ es hidrógeno, hidroxilo, alcoxilo C£₈, o alcoxilo C£₈ sustituido; R¹² es hidrógeno, hidroxilo, alcoxilo C£₈, alcoxilo C£₈ sustituido, o -O-alcanodiilo C£₈-alquilamino C£₁₂, -OC(O)-alcanodiilo C£₈-alquilamino C£₁₂, o -OC(O)NH-alcanodiilo C£₈-alquilamino C£₁₂, o una versión sustituida de cualquiera de estos grupos; o el compuesto de fórmula (4) donde: R¹⁴ es amino o hidroxilo; o alcoxilo C£₁₂, alquilamino C£₁₂, dialquil-amino C£₁₂, o una versión sustituida de cualquiera de estos grupos, o -NRᵃRᵇ, donde: Rᵃ y Rᵇ, son cada uno hidrógeno, alquilo C£₁₂, alquilo C£₁₂ sustituido, alquenilo C£₁₂, alquenilo C£₁₂ sustituido, -C(O)O-alcanodiilo C£₆-Rᶜ, -C(O)-alcanodiilo C£₆-Rᶜ, alcanodiilo C£₆-Rᶜ, o una versión sustituida de cualquiera de estos grupos; donde: Rᶜ es hidrógeno, amino, carboxilo, hidroxilo, acilo C£₈, alcoxilo C£₈, alquilamino C£₈, dialquilamino C£₈, alquilsulfonilo C£₈, arilsulfonilo C£₈, o una versión sustituida de cualquiera de estos grupos; R¹⁵ es hidrógeno, hidroxilo, alcoxilo C£₈, o alcoxilo C£₈ sustituido; R²⁰ y R²¹ son hidrógeno, alquilo C£₈, alquilo C£₈ sustituido, alcoxilo C£₈, o alcoxilo C£₈ sustituido; A² es hidrógeno o un compuesto de fórmula (5); donde: X⁵ es O, S, o NR¹⁸; donde: R¹⁸ es hidrógeno, alquilo C£₈, alquilo C£₈ sustituido, acilo C£₈, o acilo C£₈ sustituido; n es 1, 2, 3, 4, ó 5; Z², Z³ y Z⁴ son en forma independiente entre sí N o CR¹³; y R¹³ es hidrógeno, amino, carboxilo, hidroxilo, hidrazino, halo, nitro, o mercapto; alquilo C£₁₂, acilo C£₁₂, alcoxilo C£₁₂, aciloxilo C£₁₂, o una versión sustituida de cualquiera de estos grupos; o A¹ es el compuesto de fórmula (6) donde: Y¹ es alcanodiilo C£₈; o alcanodiilo C£₈ sustituido; X² y X³ se seleccionan en forma independiente entre si entre -O-, -S-, o -NR¹⁹-, donde: R¹⁹ es hidrógeno, alquilo C£₈, o alquilo C£₈ sustituido; R⁶ es arilo C£₁₈, heteroarilo C£₁₈, o una versión sustituida de cualquiera de estos grupos; R⁷ es alquilo C£₁₂ o alquilo C£₁₂ sustituido; con la salvedad de que el compuesto no sea los compuestos de fórmulas (7), (8), ó (9); o una sal aceptable farmacéuticamente del mismo.
ARP160101973A 2015-06-29 2016-06-29 Síntesis de shishijimicina a y sus análogos AR105193A1 (es)

Applications Claiming Priority (1)

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US201562186191P 2015-06-29 2015-06-29

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AR105193A1 true AR105193A1 (es) 2017-09-13

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ARP160101973A AR105193A1 (es) 2015-06-29 2016-06-29 Síntesis de shishijimicina a y sus análogos

Country Status (19)

Country Link
US (1) US10590158B2 (es)
EP (1) EP3313389A1 (es)
JP (1) JP2018525346A (es)
KR (1) KR20180053294A (es)
CN (1) CN108348489A (es)
AR (1) AR105193A1 (es)
AU (1) AU2016286071A1 (es)
BR (1) BR112017028557A2 (es)
CA (1) CA2990206A1 (es)
CL (1) CL2017003500A1 (es)
HK (1) HK1254923A1 (es)
IL (1) IL256345A (es)
MA (1) MA42273A (es)
MX (1) MX2017016885A (es)
PE (1) PE20180658A1 (es)
PH (1) PH12018500014A1 (es)
RU (1) RU2018102808A (es)
TW (1) TW201713634A (es)
WO (1) WO2017004172A1 (es)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110357785B (zh) * 2019-07-26 2020-03-24 东莞市领创环保材料科技有限公司 一种氰酸酯树脂增塑剂的制备方法
CN115197188B (zh) * 2021-04-12 2023-12-26 南开大学 一类具有五环骨架的倍半萜氢醌化合物及其制备方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5264586A (en) * 1991-07-17 1993-11-23 The Scripps Research Institute Analogs of calicheamicin gamma1I, method of making and using the same
US5261586A (en) * 1992-03-26 1993-11-16 Chen Jen Fu Yarn feeding device with a guiding flange
US5550246A (en) 1994-09-07 1996-08-27 The Scripps Research Institute Calicheamicin mimics
JP2003238584A (ja) * 2002-02-08 2003-08-27 Yamanouchi Pharmaceut Co Ltd 新規エンジイン化合物
AR048098A1 (es) * 2004-03-15 2006-03-29 Wyeth Corp Conjugados de caliqueamicina
EP2922818B1 (en) * 2012-11-24 2018-09-05 Hangzhou Dac Biotech Co., Ltd Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules

Also Published As

Publication number Publication date
IL256345A (en) 2018-02-28
MX2017016885A (es) 2018-09-06
HK1254923A1 (zh) 2019-08-02
TW201713634A (zh) 2017-04-16
BR112017028557A2 (pt) 2018-09-04
CN108348489A (zh) 2018-07-31
WO2017004172A8 (en) 2018-01-11
US10590158B2 (en) 2020-03-17
KR20180053294A (ko) 2018-05-21
JP2018525346A (ja) 2018-09-06
RU2018102808A (ru) 2019-07-30
CA2990206A1 (en) 2017-01-05
WO2017004172A1 (en) 2017-01-05
RU2018102808A3 (es) 2020-04-30
PH12018500014A1 (en) 2018-07-09
PE20180658A1 (es) 2018-04-17
AU2016286071A8 (en) 2019-08-08
AU2016286071A1 (en) 2018-02-01
US20180327439A1 (en) 2018-11-15
MA42273A (fr) 2018-05-02
CL2017003500A1 (es) 2018-04-27
EP3313389A1 (en) 2018-05-02

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