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AR127404A1 - Inhibidores de la metionina adenosiltransferasa 2a (mat2a) y usos de los mismos - Google Patents

Inhibidores de la metionina adenosiltransferasa 2a (mat2a) y usos de los mismos

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AR127404A1
AR127404A1 ARP220102842A ARP220102842A AR127404A1 AR 127404 A1 AR127404 A1 AR 127404A1 AR P220102842 A ARP220102842 A AR P220102842A AR P220102842 A ARP220102842 A AR P220102842A AR 127404 A1 AR127404 A1 AR 127404A1
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Argentina
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6alkyl
10aryl
6alkynyl
6alkenyl
6haloalkyl
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ARP220102842A
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English (en)
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Chiachun Chen
Xiao Ding
Xiaosong Liu
Qingyuan Meng
Feng Ren
Hailong Wang
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Insilico Medicine Ip Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
    • C07D413/14—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
    • C07D471/00—Heterocyclic 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
    • C07D471/02—Heterocyclic 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
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cephalosporin Compounds (AREA)

Abstract

En la presente se describen inhibidores de MAT2A y composiciones farmacéuticas que comprenden estos inhibidores. Los compuestos y composiciones de la presente son útiles para el tratamiento de una enfermedad o trastorno asociado con MAT2A. Reivindicación 1: Un compuesto de la fórmula (1) o la fórmula (2), o una sal farmacéuticamente aceptable del mismo; en donde: el Anillo A se selecciona de C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo y C₁₋₁₀heteroarilo; Z¹ es CR⁷ o N; Z² es CR⁹ o N; Z³ es CR⁶ o N; Z⁴ es CR⁶ᵃ o N; X se selecciona de -N(R⁴)-, -O- y -C(R⁵)(R⁵ᵃ)-; Y se selecciona de -N(R⁴ᵃ)-, -O- y -C(R⁵)(R⁵ᵃ)-; R¹ se selecciona de hidrógeno, halógeno, C₁₋₆alquilo, C₁₋₆haloalquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, C₁₋₉heteroarilo, -OR¹⁰, -SR¹⁰, -SF₅, -N(R¹⁰)(R¹¹), -C(O)OR¹⁰, -OC(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)OR¹³, -N(R¹²)S(O)₂R¹³, -C(O)R¹³, -S(O)R¹³, -OC(O)R¹³, -C(O)N(R¹⁰)(R¹¹), -C(O)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)R¹³, -S(O)₂R¹³, -S(O)₂N(R¹⁰)(R¹¹)-, -N=S(=O)(R¹³)₂, -S(=O)(=NH)N(R¹⁰)(R¹¹), -S(=O)(=NH)C(R¹⁰)(R¹¹), -S(=O)(=NR¹³)R¹³, -CH₂C(O)N(R¹⁰)(R¹¹), -CH₂N(R¹²)C(O)R¹³, -CH₂S(O)₂R¹³, -CH₂S(O)₂N(R¹⁰)(R¹¹), -Si(C₁₋₆alquil)₃, y -P(O)(R¹⁰)₂, en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos seleccionados de R¹⁵ᵃ; R¹ᵃ y R¹ᵇ se seleccionan independientemente de hidrógeno, halógeno, C₁₋₆alquilo, C₁₋₆haloalquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo; en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos, o tres grupos seleccionados de R¹⁵ᵃ; cada R² y cada R³ se selecciona independientemente de hidrógeno, halógeno, oxo, C₁₋₆alquilo, C₁₋₆haloalquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, C₁₋₉heteroarilo, -OR¹⁰, -SR¹⁰, -SF₅, -N(R¹⁰)(R¹¹), -C(O)OR¹⁰, -OC(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)OR¹³, -N(R¹²)S(O)₂R¹³, -C(O)R¹³, -S(O)R¹³, -OC(O)R¹³, -C(O)N(R¹⁰)(R¹¹), -C(O)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)R¹³, -S(O)₂R¹³, -S(O)₂N(R¹⁰)(R¹¹)-, -N=S(=O)(R¹³)₂, -S(=O)(=NH)N(R¹⁰)(R¹¹), -S(=O)(=NH)C(R¹⁰)(R¹¹), -S(=O)(=NR¹³)R¹³, -CH₂C(O)N(R¹⁰)(R¹¹), -CH₂N(R¹²)C(O)R¹³, -CH₂S(O)₂R¹³, -CH₂S(O)₂N(R¹⁰)(R¹¹), -Si(C₁₋₆alquil)₃, y -P(O)(R¹⁰)₂, en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos seleccionados de R¹⁵ᵇ; o R² y R³, conjuntamente con el carbono al cual están unidos, forman un C₃₋₆cicloalquilo o C₂₋₉heterocicloalquilo; R⁴ se selecciona de hidrógeno, C₁₋₆alquilo, C₁₋₆haloalquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo, en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos seleccionados de halógeno, -CN, hidroxi, C₁₋₆alquilo, C₁₋₆haloalquilo, C₁₋₆alcoxi, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo; o R⁴ y un R³ se combinan para formar un C₂₋₉heterocicloalquilo opcionalmente sustituido con uno, dos o tres grupos seleccionados de halógeno, -CN, hidroxi, C₁₋₆alquilo, C₁₋₆haloalquilo, C₁₋₆alcoxi, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo; R⁴ᵃ se selecciona de hidrógeno, C₁₋₆alquilo, C₁₋₆haloalquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo, en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos seleccionados de halógeno, -CN, hidroxi, C₁₋₆alquilo, C₁₋₆haloalquilo, C₁₋₆alcoxi, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo; o R⁴ᵃ y un R³ se combinan para formar un C₂₋₉heterocicloalquilo opcionalmente sustituido con uno, dos o tres grupos seleccionados de halógeno, -CN, hidroxi, C₁₋₆alquilo, C₁₋₆haloalquilo, C₁₋₆alcoxi, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo; R⁵ y R⁵ᵃ se seleccionan independientemente de hidrógeno, halógeno, C₁₋₆alquilo, C₁₋₆haloalquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, C₁₋₉heteroarilo, -OR¹⁰, -SR¹⁰, -SF₅, -N(R¹⁰)(R¹¹), -C(O)OR¹⁰, -OC(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)OR¹³, -N(R¹²)S(O)₂R¹³, -C(O)R¹³, -S(O)R¹³, -OC(O)R¹³, -C(O)N(R¹⁰)(R¹¹), -C(O)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)R¹³, -S(O)₂R¹³, -S(O)₂N(R¹⁰)(R¹¹)-, -N=S(=O)(R¹³)₂, -S(=O)(=NH)N(R¹⁰)(R¹¹), -S(=O)(=NH)C(R¹⁰)(R¹¹), -S(=O)(=NR¹³)R¹³, -CH₂C(O)N(R¹⁰)(R¹¹), - CH₂N(R¹²)C(O)R¹³, -CH₂S(O)₂R¹³, -CH₂S(O)₂N(R¹⁰)(R¹¹), -Si(C₁₋₆alquil)₃, y -P(O)(R¹⁰)₂, en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos seleccionados de halógeno, -CN, hidroxi, C₁₋₆alquilo, C₁₋₆haloalquilo, C₁₋₆alcoxi, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo y C₁₋₉heteroarilo; o R⁵ y un R³ se combinan para formar un C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo o C₂₋₉heteroarilo, en donde C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos seleccionados de halógeno, -CN, hidroxi, C₁₋₆alquilo, C₁₋₆haloalquilo, C₁₋₆alcoxi, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo; R⁶, R⁷, R⁸ y R⁹ se seleccionan independientemente de hidrógeno, halógeno, -CN, C₁₋₆alquilo, C₁₋₆haloalquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, C₁₋₉heteroarilo, -OR¹⁰, -SR¹⁰, -SF₅, -N(R¹⁰)(R¹¹), -C(O)OR¹⁰, -OC(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)OR¹³, -N(R¹²)S(O)₂R¹³, -C(O)R¹³, -S(O)R¹³, -OC(O)R¹³, -C(O)N(R¹⁰)(R¹¹), -C(O)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)R¹³, -S(O)₂R¹³, -S(O)₂N(R¹⁰)(R¹¹)-, -N=S(=O)(R¹³)₂, -S(=O)(=NH)N(R¹⁰)(R¹¹), -S(=O)(=NH)C(R¹⁰)(R¹¹), -S(=O)(=NR¹³)R¹³, -CH₂C(O)N(R¹⁰)(R¹¹), -CH₂N(R¹²)C(O)R¹³, -CH₂S(O)₂R¹³, -CH₂S(O)₂N(R¹⁰)(R¹¹), -Si(C₁₋₆alquil)₃, y -P(O)(R¹⁰)₂, en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos seleccionados de R¹⁵ᶜ; R⁶ᵃ se selecciona de hidrógeno, halógeno, -CN, C₁₋₆alquilo, C₁₋₆haloalquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₁₋₉heteroarilo, -OR¹⁰, -SR¹⁰, -SF₅, -N(R¹⁰)(R¹¹), -C(O)OR¹⁰, -C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)OR¹³, -N(R¹²)S(O)₂R¹³, -C(O)R¹³, -S(O)R¹³, -OC(O)R¹³, -C(O)N(R¹⁰)(R¹¹), -C(O)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)R¹³, -S(O)₂R¹³, -S(O)₂N(R¹⁰)(R¹¹)-, -N=S(=O)(R¹³)₂, -S(=O)(=NH)N(R¹⁰)(R¹¹), -S(=O)(=NH)C(R¹⁰)(R¹¹), -S(=O)(=NR¹³)R¹³, -CH₂C(O)N(R¹⁰)(R¹¹), -CH₂N(R¹²)C(O)R¹³, -CH₂S(O)₂R¹³, -CH₂S(O)₂N(R¹⁰)(R¹¹), -Si(C₁₋₆alquil)₃, y -P(O)(R¹⁰)₂, en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos seleccionados de R¹⁵ᶜ; cada R¹⁰ se selecciona independientemente de hidrógeno, C₁₋₆alquilo, C₁₋₆haloalquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo y C₁₋₉heteroarilo, en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos seleccionados de halógeno, -CN, hidroxi, C₁₋₆alquilo, C₁₋₆haloalquilo, C₁₋₆alcoxi, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo y C₁₋₉heteroarilo; cada R¹¹ se selecciona independientemente de hidrógeno, C₁₋₆alquilo y C₁₋₆haloalquilo; o R¹⁰ y R¹¹, conjuntamente con el nitrógeno al cual están unidos, forman un C₂₋₉heterocicloalquilo; cada R¹² se selecciona independientemente de hidrógeno, C₁₋₆alquilo y C₁₋₆haloalquilo; cada R¹³ se selecciona independientemente de C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo, en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos, o tres grupos seleccionados de halógeno, -CN, hidroxi, C₁₋₆alquilo, C₁₋₆haloalquilo, C₁₋₆alcoxi, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, y C₁₋₉heteroarilo; cada R¹⁴ se selecciona independientemente de halógeno, C₁₋₆alquilo, C₁₋₆haloalquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, C₁₋₉heteroarilo, -OR¹⁰, -SR¹⁰, -SF₅, -N(R¹⁰)(R¹¹), -C(O)OR¹⁰, -OC(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)OR¹³, -N(R¹²)S(O)₂R¹³, -C(O)R¹³, -S(O)R¹³, -OC(O)R¹³, -C(O)N(R¹⁰)(R¹¹), -C(O)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)R¹³, -S(O)₂R¹³, -S(O)₂N(R¹⁰)(R¹¹)-, -N=S(=O)(R¹³)₂, -S(=O)(=NH)N(R¹⁰)(R¹¹), -S(=O)(=NH)C(R¹⁰)(R¹¹), -S(=O)(=NR¹³)R¹³, -CH₂C(O)N(R¹⁰)(R¹¹), -CH₂N(R¹²)C(O)R¹³, -CH₂S(O)₂R¹³, -CH₂S(O)₂N(R¹⁰)(R¹¹), -Si(C₁₋₆alquil)₃, y -P(O)(R¹⁰)₂, en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, C₆₋₁₀arilo y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos seleccionados de R¹⁵ᵈ; cada R¹⁵ᵃ, R¹⁵ᵇ, R¹⁵ᶜ y R¹⁵ᵈ se selecciona independientemente de halógeno, oxo, -CN, C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₁₀cicloalquilo, -CH₂-C₃₋₆cicloalquilo, C₂₋₉heterocicloalquilo, -CH₂-C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, -CH₂-C₆₋₁₀arilo, C₁₋₉heteroarilo, -CH₂-C₁₋₉heteroarilo, -OR¹⁰, -SR¹⁰, -SF₅, -N(R¹⁰)(R¹¹), -C(O)OR¹⁰, -OC(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)OR¹³, -N(R¹²)S(O)₂R¹³, -C(O)R¹³, -S(O)R¹³, -OC(O)R¹³, -C(O)N(R¹⁰)(R¹¹), -C(O)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)R¹³, -S(O)₂R¹³, -S(O)₂N(R¹⁰)(R¹¹)-, -N=S(=O)(R¹³)₂, -S(=O)(=NH)N(R¹⁰)(R¹¹), -S(=O)(=NH)C(R¹⁰)(R¹¹), -S(=O)(=NR¹³)R¹³, -CH₂C(O)N(R¹⁰)(R¹¹), -CH₂N(R¹²)C(O)R¹³, -CH₂S(O)₂R¹³, -CH₂S(O)₂N(R¹⁰)(R¹¹), -Si(C₁₋₆alquil)₃, y -P(O)(R¹⁰)₂, en donde C₁₋₆alquilo, C₂₋₆alquenilo, C₂₋₆alquinilo, C₃₋₆cicloalquilo, -CH₂-C₃₋₁₀cicloalquilo, C₂₋₉heterocicloalquilo, -CH₂-C₂₋₉heterocicloalquilo, C₆₋₁₀arilo, -CH₂-C₆₋₁₀arilo, -CH₂-C₁₋₉heteroarilo, y C₁₋₉heteroarilo están opcionalmente sustituidos con uno, dos o tres grupos que se seleccionan independientemente de halógeno, oxo, -CN, C₁₋₆alquilo, C₁₋₆haloalquilo, C₁₋₆alcoxi, C₁₋₆haloalcoxi, -OR¹⁰, -SR¹⁰, -SF₅, -N(R¹⁰)(R¹¹), -C(O)OR¹⁰, -OC(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)OR¹³, -N(R¹²)S(O)₂R¹³, -C(O)R¹³, -S(O)R¹³, -OC(O)R¹³, -C(O)N(R¹⁰)(R¹¹), -C(O)C(O)N(R¹⁰)(R¹¹), -N(R¹²)C(O)R¹³, -S(O)₂R¹³, -S(O)₂N(R¹⁰)(R¹¹)-, -N=S(=O)(R¹³)₂, -S(=O)(=NH)N(R¹⁰)(R¹¹), -S(=O)(=NH)C(R¹⁰)(R¹¹), -S(=O)(=NR¹³)R¹³, -CH₂C(O)N(R¹⁰)(R¹¹), -CH₂N(R¹²)C(O)R¹³, -CH₂S(O)₂R¹³, -CH₂S(O)₂N(R¹⁰)(R¹¹) y -P(O)(R¹⁰)₂; m es 0, 1, 2, 3, 4, o 5; y n es 0, 1, 2, 3, 4, 5 o 6.
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