AR114044A1 - Composiciones y métodos para el tratamiento de trastornos en el sistema nervioso central - Google Patents

Composiciones y métodos para el tratamiento de trastornos en el sistema nervioso central

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AR114044A1
AR114044A1 ARP180103829A ARP180103829A AR114044A1 AR 114044 A1 AR114044 A1 AR 114044A1 AR P180103829 A ARP180103829 A AR P180103829A AR P180103829 A ARP180103829 A AR P180103829A AR 114044 A1 AR114044 A1 AR 114044A1
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substituted
unsubstituted
ora1
sra1
nhc
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Boyd L Harrison
Daniel La
Maria Jesus Blanco-Pillado
Francesco G Salituro
Albert J Robichaud
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Sage Therapeutics Inc
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    • C07J—STEROIDS
    • C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • C07J63/002—Expansion of ring A by one atom, e.g. A homo steroids
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    • C07J—STEROIDS
    • C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C307/00—Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C307/02—Monoamides of sulfuric acids or esters thereof, e.g. sulfamic acids
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • 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
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K31/435—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
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/19—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a saturated carbon skeleton containing rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/385—Saturated compounds containing a keto group being part of a ring
    • C07C49/487—Saturated compounds containing a keto group being part of a ring containing hydroxy groups
    • C07C49/507—Saturated compounds containing a keto group being part of a ring containing hydroxy groups polycyclic
    • C07C49/513—Saturated compounds containing a keto group being part of a ring containing hydroxy groups polycyclic a keto group being part of a condensed ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J61/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by contraction of only one ring by one or two atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • C07J63/004—Expansion of ring B by one atom, e.g. B homo steroids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • C07J63/006—Expansion of ring C by one atom, e.g. C homo steroids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/40—Ortho- or ortho- and peri-condensed systems containing four condensed rings
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/40—Ortho- or ortho- and peri-condensed systems containing four condensed rings
    • C07C2603/42—Ortho- or ortho- and peri-condensed systems containing four condensed rings containing only six-membered rings

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Compuestos de la fórmula (1) y sus sales farmacéuticamente aceptables, donde t, R⁷, R³, R⁹, R⁶ᵃ, R⁶ᵇ, R¹¹ᵃ, R¹¹ᵇ, R¹⁵ᵃ, R¹⁵ᵇ, R¹⁶ᵃ, R¹⁶ᵇ, R¹⁷ᵃ, R¹⁷ᵇ, R¹⁸ᵃ, R¹⁸ᵇ, R¹⁹ᵃ, R¹⁹ᵇ, R⁵ᵃ, R⁵ᵇ, R⁸ y R¹³ tienen los valores que se definen en la memoria descriptiva. Composiciones farmacéuticas que comprenden un compuesto de fórmula (1) y métodos para usar los compuestos, por ejemplo, en el tratamiento de trastornos relacionados con el sistema nervioso central. Reivindicación 1: Un compuesto de fórmula (1) o una sal aceptable farmacéuticamente del mismo; donde: t es 1 ó 2; R⁷ es hidrógeno o metilo, o cuando ⁻ ⁻ ⁻ ⁻ ⁻ ⁻ es una unión doble, R⁷ se encuentra ausente; R³ es hidrógeno, alquilo sustituido o no sustituido, alquenilo sustituido o no sustituido, alquinilo sustituido o no sustituido, carbociclilo sustituido o no sustituido, heterociclo sustituido o no sustituido, arilo sustituido o no sustituido, o heteroarilo sustituido o no sustituido; R⁹ es hidrógeno o alquilo sustituido o no sustituido; cada uno de R⁶ᵃ y R⁶ᵇ es en forma independiente hidrógeno, halógeno, ciano, hidroxilo, alquilo sustituido o no sustituido, alquenilo sustituido o no sustituido, o alquinilo sustituido o no sustituido, o R⁶ᵃ y R⁶ᵇ se unen para formar un grupo oxo (=O); cada uno de R¹¹ᵃ, R¹¹ᵇ, R¹⁵ᵃ, R¹⁵ᵇ, R¹⁶ᵃ, R¹⁶ᵇ, R¹⁷ᵃ, R¹⁷ᵇ, R¹⁸ᵃ, R¹⁸ᵇ, R¹⁹ᵃ, o R¹⁹ᵇ es en forma independiente hidrógeno, halógeno, ciano, hidroxilo, alquilo sustituido o no sustituido, alquenilo sustituido o no sustituido, heterociclo sustituido o no sustituido, o alquinilo sustituido o no sustituido, -ORD¹, -OC(=O)RD¹, -NH₂, -N(RD¹)₂, o -NRD¹C(=O)RD¹, donde cada instancia de RD¹ es en forma independiente hidrógeno, alquilo sustituido o no sustituido, alquenilo sustituido o no sustituido, alquinilo sustituido o no sustituido, carbociclilo sustituido o no sustituido, heterociclo sustituido o no sustituido, arilo sustituido o no sustituido, o heteroarilo sustituido o no sustituido, un grupo protector de oxigeno cuando está unido a un átomo de oxígeno, un grupo protector de nitrógeno cuando está unido a un átomo de nitrógeno, o dos grupos RD¹ se unen para formar un anillo heterocíclico sustituido o no sustituido; o uno cualquiera de R¹¹ᵃ y R¹¹ᵇ, R¹⁵ᵃ y R¹⁵ᵇ, R¹⁶ᵃ y R¹⁶ᵇ, R¹⁷ᵃ y R¹⁷ᵇ, y R¹⁸ᵃ y R¹⁸ᵇ se unen para formar un grupo oxo (=O); cada uno de R⁵ᵃ, R⁵ᵇ, R⁸ y R¹³ son cada uno en forma independiente hidrógeno, halógeno, ciano, alquilo sustituido o no sustituido, alquenilo sustituido o no sustituido, alquinilo sustituido o no sustituido, carbociclilo sustituido o no sustituido, heterociclo sustituido o no sustituido, arilo sustituido o no sustituido, heteroarilo sustituido o no sustituido, -ORA¹, -SRA¹, -N(RA¹)₂, -N(RA¹), -CN(RA¹)₂, -C(O)RA¹, -C(=O)N(RA¹)₂, -OC(=O)RA¹, -OC(=O)ORA¹, OC(=O)SRA¹, -OC(=O)N(RA¹)₂, -SC(=O)RA², -SC(=O)ORA¹, -SC(=O)SRA¹, -SC(=O)N(RA¹)₂, -NHC(=O)RA¹, -NHC(=O)ORA¹, -NHC(=O)SRA¹, -NHC(=O)N(RA¹)₂, -OS(=O)₂RA², -OS(=O)₂ORA¹, -S-S(=O)₂RA², -S-S(=O)₂ORA¹, -S(=O)RA², -SO₂RA², o -S(=O)₂ORA¹, donde cada instancia de RA¹ es en forma independiente hidrógeno, alquilo sustituido o no sustituido, alquenilo sustituido o no sustituido, alquinilo sustituido o no sustituido, carbociclilo sustituido o no sustituido, heterociclo sustituido o no sustituido, arilo sustituido o no sustituido, heteroarilo sustituido o no sustituido, un grupo protector de oxígeno cuando está unido a un átomo de oxígeno, un grupo protector de nitrógeno cuando está unido a un átomo de nitrógeno, -SO₂RA², -C(O)RA², o dos grupos RA¹ se unen para formar un anillo heterocíclico o heteroarilo sustituido o no sustituido; y RA² es alquilo sustituido o no sustituido, alquenilo sustituido o no sustituido, alquinilo sustituido o no sustituido, carbociclilo sustituido o no sustituido, heterociclo sustituido o no sustituido, arilo sustituido o no sustituido, o heteroarilo sustituido o no sustituido; o R⁸ y R¹³ se unen para formar un grupo oxo (=O), donde cuando R⁸ y R¹³ se unen para formar un grupo oxo (=O), R³ es alquilo sustituido o no sustituido, alquenilo sustituido o no sustituido, alquinilo sustituido o no sustituido, carbociclilo sustituido o no sustituido, heterociclo sustituido o no sustituido, arilo sustituido o no sustituido, o heteroarilo sustituido o no sustituido; y donde al menos uno de R⁵ᵃ, R⁵ᵇ, R⁸ y R¹³ debe ser etilo, alquilo sustituido, alquenilo sustituido o no sustituido, alquinilo sustituido o no sustituido, carbociclilo sustituido o no sustituido, heterociclo sustituido o no sustituido, arilo sustituido o no sustituido, heteroarilo sustituido o no sustituido, -ORA¹, -SRA¹, -N(RA¹)₂, -N(RA¹), -CN(RA¹)₂, -C(O)RA¹, -C(=O)N(RA¹)₂, -OC(=O)RA¹, -OC(=O)ORA¹, -OC(=O)SRA¹, -OC(=O)N(RA¹)₂, -SC(=O)RA², -SC(=O)ORA¹, -SC(=O)SRA¹, -SC(=O)N(RA¹)₂, -NHC(=O)RA¹, -NHC(=O)ORA¹, -NHC(=O)SRA¹, -NHC(=O)N(RA¹)₂, -OS(=O)₂RA², -OS(=O)₂ORA¹, -S-S(=O)₂RA², -S-S(=O)₂ORA¹, -S(=O)RA², -SO₂RA², o -S(=O)₂ORA¹; donde R⁸ y R¹³ no pueden ser ambos metilo; donde ⁻ ⁻ ⁻ ⁻ ⁻ ⁻ representa una unión simple o doble, con la salvedad de que si hay una unión doble en el anillo B, entonces uno de R⁶ᵃ o R⁶ᵇ y R⁷ se encuentra ausente.
ARP180103829A 2017-12-22 2018-12-21 Composiciones y métodos para el tratamiento de trastornos en el sistema nervioso central AR114044A1 (es)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201762610067P 2017-12-22 2017-12-22
US201762612164P 2017-12-29 2017-12-29
US201762612070P 2017-12-29 2017-12-29
US201762611977P 2017-12-29 2017-12-29
US201762612067P 2017-12-29 2017-12-29
US201862765164P 2018-08-17 2018-08-17
US201862728499P 2018-09-07 2018-09-07
US201862737559P 2018-09-27 2018-09-27
US201862754977P 2018-11-02 2018-11-02

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AR (1) AR114044A1 (es)
AU (2) AU2018392093B2 (es)
BR (1) BR112020012761A2 (es)
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