AR103598A1 - Ácidos bicíclicos[4,6,0]hidroxámicos como inhibidores de hdac - Google Patents

Ácidos bicíclicos[4,6,0]hidroxámicos como inhibidores de hdac

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Publication number
AR103598A1
AR103598A1 ARP160100294A ARP160100294A AR103598A1 AR 103598 A1 AR103598 A1 AR 103598A1 AR P160100294 A ARP160100294 A AR P160100294A AR P160100294 A ARP160100294 A AR P160100294A AR 103598 A1 AR103598 A1 AR 103598A1
Authority
AR
Argentina
Prior art keywords
alkyl
aryl
cycloalkyl
cycloalkenyl
independently
Prior art date
Application number
ARP160100294A
Other languages
English (en)
Inventor
Lancia David Jr
Rudnitskaya Aleksandra
Yee Ng Pui
Zheng Xiaozhang
Original Assignee
Forma Therapeutics 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 Forma Therapeutics Inc filed Critical Forma Therapeutics Inc
Publication of AR103598A1 publication Critical patent/AR103598A1/es

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Classifications

    • 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
    • C07D413/06Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • C07D267/00Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D267/22Eight-membered rings

Abstract

Inhibidores dependientes de zinc histona desacetilasas (HDAC) útiles en el tratamiento de enfermedades o trastornos asociados con HDAC6. Reivindicación 1: Un compuesto de fórmula (1), o su sal farmacéuticamente aceptable, profármaco, solvato, hidrato, tautómero o isómero, en donde: X¹ y X² son cada uno independientemente CR¹R², NR³, O, C=O, SO₂, S(O) o S; X³, X⁴ y X⁵ son cada uno independientemente CR¹R², C=O, S(O) o SO₂; Y¹ y Y⁴ son cada uno independientemente N o CR; Y² y Y³ son cada uno independientemente N o CR¹ cuando no se unen a -C(O)NHOH y Y² y Y³ son C cuando se unen a -C(O)NHOH; L es un enlace, -(CR¹R²)ₙ-, -C(O)-, -C(O)O-, -C(O)NR³-, -S(O)₂-, -S(O)₂NR³-, -S(O)-, -S(O)NR³-, -C(O)(CR¹R²)ₙO-, o -C(O)(CR¹R²)ₙ-; R es independiente en cada ocurrencia, -H, -alquilo C₁₋₆, -alquenilo C₂₋₆, -cicloalquenilo C₄₋₈, -alquinilo C₂₋₆, -cicloalquilo C₃₋₈, -espirociclo C₅₋₁₂, heterociclilo, espiroheterociclilo, aril o heteroarilo que contiene 1 - 5 heteroátomos seleccionados del grupo que consistente de N, S, P y O, en donde cada alquilo, alquenilo, cicloalquenilo, alquinilo, cicloalquilo, espirociclo, heterociclilo, espiroheterociclilo, arilo, o heteroarilo es opcionalmente sustituido con uno o más de -OH, halógeno, oxo, -NO₂, -CN, -R¹, -R², -OR³, -NHR³, -NR³R⁴, -S(O)₂NR³R⁴, -S(O)₂R¹, -C(O)R¹, o -CO₂R¹, -NR³S(O)₂R¹, -S(O)R¹, -S(O)NR³R⁴, -NR³S(O)R¹, heterociclo, arilo, o heteroarilo siempre que cuando L sea -C(O)- el espiroheterociclilo no se una a L vía un átomo de nitrógeno; R¹ y R² son independientemente y en cada ocurrencia, -H, -R³, -R⁴, alquilo -C₁₋₆, -alquenilo C₂₋₆, -cicloalquenilo C₄₋₈, -alquinilo C₂₋₆, -cicloalquilo C₃₋₈, heterociclilo, arilo, heteroarilo que contiene 1 - 5 heteroátomos seleccionados del grupo que consiste de N, S, P, u O, -OH, halógeno, -NO₂, -CN, -NH-alquilo C₁₋₆, -N(alquilo C₁₋₆)₂, -S(O)₂N(alquilo C₁₋₆)₂, -N(alquilo C₁₋₆)S(O)₂R⁵, -S(O)₂-(alquilo C₁₋₆), -(alquilo C₁₋₆)S(O)₂R⁵, -C(O)alquilo C₁₋₆, -CO₂-alquilo C₁₋₆, -N(alquilo C₁₋₆)S(O)₂alquilo C₁₋₆, o -(CHR⁵)ₙNR³R⁴, en donde cada alquilo, alquenilo, cicloalquenilo, alquinilo, cicloalquilo, heterociclilo, arilo, o heteroarilo es opcionalmente sustituido con uno o más sustituyentes seleccionados de -OH, halógeno, -NO₂, oxo, -CN, -R⁵, -OR³, -NHR³, NR³R⁴, -S(O)₂N(R³)₂-, -S(O)₂R⁵, -C(O)R⁵, -CO₂R⁵, -NR³S(O)₂R⁵, -S(O)R⁵, -S(O)NR³R⁴, -NR³S(O)R⁵, heterociclo, arilo, o heteroarilo que contiene 1 - 5 heteroátomos seleccionados del grupo que consiste de N, S, P, y O; o R¹ y R² se pueden combinar con el átomo de carbono al que ambos se unen para formar un espirociclo, espiroheterociclo o un espirocicloalquenilo; o R¹ y R², cuando están en átomos adyacentes, pueden combinar para formar un heterociclo, cicloalquilo, arilo, heteroarilo que contiene 1 - 5 heteroátomos seleccionados del grupo que consiste de N, S, P y O ó cicloalquenilo; o R¹ y R², cuando están en átomos no adyacentes, pueden combinarse para formar un puente de cicloalquilo o heterocicloalquilo; en donde el puente entre X¹ y X⁴ no puede contener exactamente un carbono; R³ y R⁴ son independientemente, y en cada ocurrencia, -H, alquilo -C₁₋₆, -alquenilo C₂₋₆, -cicloalquenilo C₄₋₈, -alquinilo C₂₋₆, -cicloalquilo C₃₋₈, heterociclilo, arilo, heteroarilo que contiene 1 - 5 heteroátomos seleccionados del grupo que consiste de N, S, P u O, -S(O)₂N(alquilo C₁₋₆)₂, S(O)₂(alquilo C₁₋₆), -(alquilo C₁₋₆)S(O)₂R⁵, -C(O)alquilo C₁₋₆, -CO₂-alquilo C₁₋₆, o -(CHR⁵)ₙN(alquilo C₁₋₆), en donde cada alquilo, alquenilo, cicloalquenilo, alquinilo, cicloalquilo, heterociclilo, arilo y heteroarilo es opcionalmente sustituido con uno lo más sustituyentes seleccionados de -OH, halógeno, -NO₂, oxo, -CN, -R⁵, -O-alquilo C₁₋₆, -NH-alquilo C₁₋₆, N(alquilo C₁₋₆)₂, -S(O)₂N(alquilo C₁₋₆)₂, -S(O)₂NH-alquilo C₁₋₆, -C(O)alquilo C₁₋₆, -CO₂-alquilo C₁₋₆, -N(alquilo C₁₋₆)S(O)₂alquilo C₁₋₆, -S(O)R⁵, -S(O)N(alquilo C₁₋₆)₂, -N(alquilo C₁₋₆)S(O)R⁵, heterocíclico, arilo, o heteroarilo que contiene 1 - 5 heteroátomos seleccionados del grupo que consiste de N, S, P u O; R⁵ es independientemente, y en cada ocurrencia, -H, alquilo -C₁₋₆, -alquenilo C₂₋₆, -cicloalquenilo C₃₋₈, -alquinilo C₂₋₆, -cicloalquilo C₃₋₈, heterocíclico, arilo, heteroarilo, OH, halógeno, -NO₂, -CN, -NH-alquilo C₁₋₆, -N(alquilo C₁₋₆)₂, -S(O)₂N(alquilo C₁₋₆), -S(O)₂(alquilo C₁₋₆)₂, -S(O)₂-alquilo C₁₋₆, -C(O)alquilo C₁₋₆, -CO₂-alquilo C₁₋₆, -N(alquilo C₁₋₆)SO₂-alquilo C₁₋₆, -S(O)(alquilo C₁₋₆), -S(O)N(alquilo C₁₋₆)₂, -N(alquilo C₁₋₆)S(O)(alquilo C₁₋₆) o (CH₂)ₙN(alquilo C₁₋₆)₂; n es independientemente, y en cada ocurrencia, un número entero de 0 a 6; y siempre que X¹, X², X³, X⁴ y X⁵ no sean todos CR¹R² al mismo tiempo.
ARP160100294A 2015-02-02 2016-02-02 Ácidos bicíclicos[4,6,0]hidroxámicos como inhibidores de hdac AR103598A1 (es)

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US201562110719P 2015-02-02 2015-02-02

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US (5) US10183934B2 (es)
AR (1) AR103598A1 (es)
TW (1) TW201636329A (es)
WO (1) WO2016126726A1 (es)

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