AR093339A1 - Analogos de spliceostatina y metodos para su preparacion - Google Patents

Analogos de spliceostatina y metodos para su preparacion

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Publication number
AR093339A1
AR093339A1 ARP130104017A ARP130104017A AR093339A1 AR 093339 A1 AR093339 A1 AR 093339A1 AR P130104017 A ARP130104017 A AR P130104017A AR P130104017 A ARP130104017 A AR P130104017A AR 093339 A1 AR093339 A1 AR 093339A1
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Argentina
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alkyl
independently selected
nrr
group
hydrogen
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ARP130104017A
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English (en)
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Pfizer
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    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
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    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/453—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
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    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
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    • A61K47/6869—Medicinal 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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate
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    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
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  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Reproductive Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Pyrane Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La presente se refiere a análogos de spliceostatina citotóxicos y derivados, a sus conjugados farmacológicos de anticuerpos y a métodos para usarlos para tratar enfermedades médicas que incluyen cáncer. Reivindicación 1: Un compuesto de la fórmula (1), en donde: una línea de puntos representa un enlace opcional; cada X¹ está seleccionado, de modo independiente, del grupo que consiste en: -O-, -S- y -NR-; cada X² está seleccionado, de modo independiente, del grupo que consiste en: -O-, -S- y -NR-; R¹ está seleccionado del grupo que consiste en: -R, -OR, -OCOR¹³, -OCONR¹⁴R¹⁵, -OCON(R¹⁴)NR(R¹⁵), =O (doble enlace con oxígeno) y -NR¹⁴R¹⁵; R² y R³ están seleccionados, de modo independiente, del grupo que consiste en: hidrógeno y alquilo C₁₋₆; R⁴ y R⁵ están seleccionados, de modo independiente, del grupo que consiste en: hidrógeno, -OR, -NR¹⁴R¹⁵ y oxo; R⁶ y R⁷ están seleccionados, de modo independiente, del grupo que consiste en: hidrógeno, halógeno, hidroxilo y alquilo C₁₋₆ opcionalmente sustituido con 1 - 3 sustituyentes seleccionados, de modo independiente, de hidroxilo y halógeno, R⁶ y R⁷ forman, junto con el átomo de carbono al que están ligados, un alquilideno C₂₋₅ opcionalmente sustituido con 1 - 3 sustituyentes seleccionados, de modo independiente, de R, R⁶ y R⁷ son juntos oxo o R⁶ y R⁷ forman, junto con el átomo de carbono al que están ligados, un resto de heterocicloalquilo de 3 a 5 miembros que comprende 1 ó 2 heteroátomos seleccionados, de modo independiente, del grupo que consiste en oxígeno, nitrógeno y azufre, en donde dicho resto de heterocicloalquilo puede estar opcionalmente sustituido con uno a tres sustituyentes seleccionados, de modo independiente, de R; R⁸ es hidrógeno, alquilo C₁₋₆ u -OR; R⁹ está seleccionado, de modo independiente, de hidrógeno, -alquilo C₁₋₆, -(C(R)₂)ₘ-C(O)OR, -(C(R)₂)ₘ-C(O)NR¹⁴R¹⁵, -(C(R)₂)ₘ-NR¹⁴R¹⁵, -(C(R)₂)ₘ-N(R)COR¹³, -(C(R)₂)ₘ-C(O)-SR, -(C(R)₂)ₘ-C(O)NR¹⁴N(R)R¹⁵, -(C(R)₂)ₘ-NR-C(O)-NR¹⁴R¹⁵ y -(C(R)₂)ₘ-NR¹⁴N(R)R¹⁵; R¹³ está seleccionado del grupo que consiste en hidrógeno, alquilo C₁₋₆, carbociclilo C₃₋₈, heterociclilo C₃₋₈, alquil C₁₋₆-arilo C₆₋₁₄, alquil C₁₋₆-heteroarilo C₅₋₁₄, en donde R¹³ está opcionalmente sustituido con -NRR o -SO₂NRR; cada R¹⁴ y R¹⁵ está seleccionado, de modo independiente, del grupo que consiste en: hidrógeno, hidroxilo, -NRR, -NRNR₂, -carbociclilo C₃₋₁₀, -alquilen C₁₋₆-carbociclilo C₃₋₁₀, -heterociclilo C₃₋₁₀, -alquilen C₁₋₆-heterociclilo C₃₋₁₀, -(CH₂CH₂O)₁₋₆CH₂CH₂C(O)OR, -(CH₂CH₂O)₁₋₆CH₂CH₂NRR, -alquilo C₁₋₆, arilo C₆₋₁₄, -alquilen C₁₋₆-arilo C₆₋₁₄ y -heteroarilo C₅₋₁₄; o R¹⁴ y R¹⁵, junto con el átomo o los átomos a los que están unidos, forman un anillo heterociclilo C₃₋₁₀, en donde R¹⁴, R¹⁵ o ambos o un anillo formado con R¹⁴ y R¹⁵, están opcionalmente sustituidos con -(C(R)₂)ₘ-R¹⁸ donde cada R¹⁸ está seleccionado, de modo independiente, de (i) -NRR, (ii) -C(NRR)(C(O)OR), (iii) -S-R, (iv) arilo o heteroarilo opcionalmente sustituido con uno o varios de halógeno, -CF₃, -C(R)₂)ₘ-NRR o -(C(R)₂)ₘ-SO₂NRR, (v) -SO₂R, (vi) -S-S-alquil C₁₋₆-C(O)OR, (vii) -SO₂NRR, (viii) -C(O)NRR, (ix) -C(O)OR, (x) -cicloalquilo C₄₋₆ opcionalmente sustituido con -NRR, -SO₂NRR o -NR-C(O)(CH₂)₀₋₆NRR, (xi) -R, (xii) -OR, (xiii) -N(R)NRR, (xiv) -C(O)N(R)NRR, -(C(R)₂)ₘ-O-NRR y -S-S-alquil C₁₋₆-NRR; cada R está seleccionado, de modo independiente, del grupo que consiste en: hidrógeno y -alquilo C₁₋₆; y cada m es, de modo independiente, 0, 1, 2 ó 3; o una de sus sales farmacéuticamente aceptables.
ARP130104017A 2012-11-05 2013-11-04 Analogos de spliceostatina y metodos para su preparacion AR093339A1 (es)

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