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AR108011A1 - Moduladores receptores de estrógenos - Google Patents

Moduladores receptores de estrógenos

Info

Publication number
AR108011A1
AR108011A1 ARP170100788A ARP170100788A AR108011A1 AR 108011 A1 AR108011 A1 AR 108011A1 AR P170100788 A ARP170100788 A AR P170100788A AR P170100788 A ARP170100788 A AR P170100788A AR 108011 A1 AR108011 A1 AR 108011A1
Authority
AR
Argentina
Prior art keywords
optionally substituted
alkyl
hydrogen
group
cycloalkyl
Prior art date
Application number
ARP170100788A
Other languages
English (en)
Inventor
Rakesh Kumar Sit
Joseph Robert Pinchman
Kevin Duane Bunker
Chad Daniel Hopkins
Sayee Gajanan Hegde
Deborah Helen Slee
Peter Qinhua Huang
Original Assignee
Kalyra Pharmaceuticals Inc
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 Kalyra Pharmaceuticals Inc filed Critical Kalyra Pharmaceuticals Inc
Publication of AR108011A1 publication Critical patent/AR108011A1/es

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/438The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/24Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30Oestrogens
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/002Heterocyclic compounds
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/732Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/738Esters of keto-carboxylic acids or aldehydo-carboxylic acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/74Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C69/757Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/10Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/10Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • 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
    • 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
    • C07D471/12Heterocyclic 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
    • C07D471/14Ortho-condensed systems
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07Optical isomers
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00Systems containing two condensed rings
    • C07C2602/36Systems containing two condensed rings the rings having more than two atoms in common
    • C07C2602/38Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing five carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00Systems containing at least three condensed rings
    • C07C2603/56Ring systems containing bridged rings
    • C07C2603/58Ring systems containing bridged rings containing three rings
    • C07C2603/60Ring systems containing bridged rings containing three rings containing at least one ring with less than six members
    • C07C2603/62Ring systems containing bridged rings containing three rings containing at least one ring with less than six members containing three- or four-membered rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Endocrinology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Indole Compounds (AREA)
  • Steroid Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Compuestos derivados de indolpirimidina utilizables en el tratamiento del cáncer de mama. Se proveen además, intermediarios para su síntesis. Reivindicación 1: Un compuesto de la fórmula (1), o una sal farmacéuticamente aceptable del mismo, en donde: X¹, Y¹ y Z¹ son cada uno independientemente C o N; con la primera salvedad de que por lo menos uno de X¹, Y¹ y Z¹ es N; con la segunda salvedad de que cada uno de X¹, Y¹ y Z¹ es neutro; con la tercera salvedad de que dos de las líneas de puntos indican uniones doble; con la cuarta salvedad de que las valencias de X¹, Y¹ y Z¹ puede ser satisfechas cada una independientemente mediante acople a un sustituyente seleccionado de H y R¹²; X² es O, NH o S; A¹ se selecciona del grupo que consiste de un cicloalquilo opcionalmente sustituido, un arilo opcionalmente sustituido, un heteroarilo opcionalmente sustituido y un heterociclilo opcionalmente sustituido; R¹ se selecciona del grupo que consiste de un alquilo C₁₋₆ opcionalmente sustituido, un cicloalquilo opcionalmente sustituido, un cicloalquenilo opcionalmente sustituido, un arilo opcionalmente sustituido, un heteroarilo opcionalmente sustituido, un heterociclilo opcionalmente sustituido, un cicloalquil(C₁₋₆ alquilo) opcionalmente sustituido, un cicloalquenil(C₁₋₆ alquilo) opcionalmente sustituido, un aril(C₁₋₆ alquilo) opcionalmente sustituido, un heteroaril(C₁₋₆ alquilo) opcionalmente sustituido y un heterociclil(C₁₋₆ alquilo) opcionalmente sustituido; R² y R³ cada uno independientemente se selecciona del grupo que consiste de hidrógeno, halógeno, un C₁₋₆ alquilo opcionalmente sustituido y un C₁₋₆ haloalquilo opcionalmente sustituido; o R² y R³ junto con el carbono al cual R² y R³ se acoplan forman un cicloalquilo opcionalmente sustituido, un cicloalquenilo opcionalmente sustituido o un heterociclilo opcionalmente sustituido; R⁴ y R⁵ cada uno se selecciona independientemente del grupo que consiste de hidrógeno, halógeno, un C₁₋₆ alquilo opcionalmente sustituido y un C₁₋₆ haloalquilo opcionalmente sustituido; o R⁴ y R⁵ junto con el carbono al cual R⁴ y R⁵ se acoplan forman un cicloalquilo opcionalmente sustituido, un cicloalquenilo opcionalmente sustituido o un heterociclilo opcionalmente sustituido; R⁶, R⁷, R⁸ y R⁹ cada uno independientemente se selecciona del grupo que consiste de hidrógeno, halógeno, hidroxi, un alquilo opcionalmente sustituido, un alcoxi opcionalmente sustituido, un haloalquilo opcionalmente sustituido, una amina mono-sustituida opcionalmente sustituida y una amina di-sustituida opcionalmente sustituida; R¹⁰ es hidrógeno, halógeno, un alquilo opcionalmente sustituido o un cicloalquilo opcionalmente sustituido; R¹¹ es hidrógeno o un C₁₋₆ alquilo opcionalmente sustituido; y R¹² es hidrógeno, halógeno, un C₁₋₃ alquilo opcionalmente sustituido, un C₁₋₃ haloalquilo opcionalmente sustituido o un C₁₋₃ alcoxi opcionalmente sustituido; siempre que cuando R¹¹ sea hidrógeno o metilo, X¹ es NH, Y¹ y Z¹ cada uno es C, X² es O, A¹ es un fenilo, 2-fluorofenilo, o 2,6-difluorofenilo, tanto R² como R³ son metilo o uno de R² y R³ es hidrógeno y el otro de R² y R³ es metilo, y R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ y R¹⁰ cada uno es hidrógeno, entonces R¹ no podrá ser 2-hidroxietilo, 2-metilpropilo, 2-fluoro-2-metilpropilo, 3-fluoro-2-metilpropilo, 3-hidroxi-2-metilpropilo o 2-fluoro-3-hidroxi-2-metilpropilo. Reivindicación 43: Un compuesto seleccionado del grupo que consiste de los restos del grupo de fórmulas (2). Reivindicación 44: Un compuesto seleccionado del grupo que consiste de los compuesto de fórmula (3) y (4). Reivindicación 45: Un compuesto de la fórmula (5). Reivindicación 46: Un compuesto de la fórmula (6).
ARP170100788A 2016-04-01 2017-03-30 Moduladores receptores de estrógenos AR108011A1 (es)

Applications Claiming Priority (1)

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US201662317254P 2016-04-01 2016-04-01

Publications (1)

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AR108011A1 true AR108011A1 (es) 2018-07-04

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Country Link
US (5) US20190142811A1 (es)
EP (1) EP3442971B1 (es)
JP (2) JP6926189B2 (es)
KR (2) KR20220071293A (es)
CN (4) CN112679495B (es)
AR (1) AR108011A1 (es)
AU (3) AU2017242027B2 (es)
CA (1) CA3017388C (es)
ES (1) ES2991862T3 (es)
IL (3) IL285318B (es)
MX (2) MX392461B (es)
RU (1) RU2738646C2 (es)
SG (1) SG11201807708SA (es)
TW (2) TW202235418A (es)
WO (1) WO2017172957A1 (es)

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