ES2575995T3 - Inhibidores de ERK para trastornos del desarrollo de la conectividad neuronal - Google Patents

Inhibidores de ERK para trastornos del desarrollo de la conectividad neuronal Download PDF

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Publication number
ES2575995T3
ES2575995T3 ES11815379.0T ES11815379T ES2575995T3 ES 2575995 T3 ES2575995 T3 ES 2575995T3 ES 11815379 T ES11815379 T ES 11815379T ES 2575995 T3 ES2575995 T3 ES 2575995T3
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amino
hydroxyethoxy
carboxamide
fluoro
chloro
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ES11815379.0T
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English (en)
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Mark A. Smith
Michael Snape
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Case Western Reserve University
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Case Western Reserve University
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    • 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
    • A61K31/275—Nitriles; Isonitriles
    • A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
    • 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
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
    • 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
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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

Abstract

Compuestos inhibidores de ERK en solitario o en combinación que evitan anomalías en la conectividad neuronal; o una sal farmacéuticamente aceptable y/o uno o más estereoisómeros de los mismos; para su uso en el tratamiento de síndrome del cromosoma X frágil o trastornos del espectro autista asociados a anomalías de ERK, en los que el inhibidor de ERK se selecciona entre el grupo que consiste en 2-(2-amino-3- metoxifenil)-4H-cromen-4-ona, (2Z,3Z)-bis{amino[(2-aminofenil)sulfanil]metilideno}butanodinitrilo, 5-[(4-bromo-2- clorofenil)amino]-4-fluoro-N-(2-hidroxietoxi)-1-metil-1H-bencimidazol-6-carboxamida, 2-[(2-fluoro-4-yodofenil)amino]- N-(2-hidroxietoxi)-1,5-dimetil-6-oxo-1,6-dihidropiridin-3-carboxamida, 2-(4-cloro-2-fluoro-anilino)-N-(2-hidroxietoxi)- 1,5-dimetil-6-oxo-piridin-3-carboxamida, 2-[(2-cloro-4-yodofenil)amino]-N-(ciclopropilmetoxi)-3,4-difluorobenzamida, (3R,4R)-4-(3,4-Dimetoxibencil)-3-(4-hidroxi-3-metoxibencil)dihidrofuran-2(3H)-ona, (2Z)-3-amino-3-[(4- aminofenil)sulfanil]-2-[2-(trifluorometil)fenil]prop-2-enenitrilo, hipericina, 3-(3-amino-2H-pirazolo[3,4-c]piridazin-5-il)-2- fenil-3H-pirazolo[ 1,5-a]piridin-8-io, y ácido 2-cloro-4-{[2-{[(2R)-1-hidroxi-3-metilbutan-2-il]amino}-9-(propan-2-il)-9Hpurin- 6-il]amino}benzoico.

Description

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Análisis estadístico
Los datos se analizaron por análisis de varianza (ANOVA) seguido de comparaciones post-hoc con pruebas de Fisher cuando fue apropiado. Un efecto se consideró significativo si p < 0,05. Los datos se presentan como la media  error estándar de la media.
RESULTADOS
Latencia de convulsiones
Los efectos de MPEP y alcohol perílico sobre la latencia de aparición de convulsiones se muestran en la figura 6. El análisis ANOVA descubrió un efecto del tratamiento significativo. Un análisis post hoc mostró que MPEP y alcohol perílico (25 y 50 mg/kg) aumentaron la latencia de convulsiones en comparación con el vehículo respectivo.
Latencia del paro respiratorio
Los efectos de MPEP y alcohol perílico sobre la latencia del paro respiratorio (y posterior muerte) se muestran en la figura 7. El análisis ANOVA descubrió un efecto del tratamiento significativo. El análisis post hoc descubrió que MPEP y alcohol perílico (25 y 50 mg/kg) prolongaron significativamente la latencia del paro respiratorio en comparación con el vehículo respectivo. Los ratones tratados con MPEP (30 mg/kg) no mostraron dificultad respiratoria durante los ensayos y, por lo tanto, a todos se les dio una latencia de 240 s.
Escala de convulsiones media
Los efectos de MPEP y alcohol perílico sobre la escala de convulsiones media se muestran en la figura 8. El análisis ANOVA descubrió un efecto del tratamiento significativo. Un análisis post hoc mostró que, en comparación con el vehículo, MPEP y alcohol perílico (25 y 50 mg/kg) redujeron significativamente la escala de convulsiones.
16

Claims (1)

  1. imagen1
ES11815379.0T 2010-08-05 2011-08-05 Inhibidores de ERK para trastornos del desarrollo de la conectividad neuronal Active ES2575995T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US37085410P 2010-08-05 2010-08-05
US370854P 2010-08-05
US40536910P 2010-10-21 2010-10-21
US405369P 2010-10-21
PCT/US2011/046773 WO2012019113A2 (en) 2010-08-05 2011-08-05 Inhibitors of erk for developmental disorders of neuronal connectivity

Publications (1)

Publication Number Publication Date
ES2575995T3 true ES2575995T3 (es) 2016-07-04

Family

ID=45560094

Family Applications (1)

Application Number Title Priority Date Filing Date
ES11815379.0T Active ES2575995T3 (es) 2010-08-05 2011-08-05 Inhibidores de ERK para trastornos del desarrollo de la conectividad neuronal

Country Status (8)

Country Link
US (1) US20150141380A1 (es)
EP (1) EP2600862B1 (es)
KR (1) KR20130113430A (es)
CN (1) CN103221043B (es)
AU (1) AU2011285611B2 (es)
CA (1) CA2807510A1 (es)
ES (1) ES2575995T3 (es)
WO (1) WO2012019113A2 (es)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10835513B2 (en) * 2013-06-28 2020-11-17 The Regents Of The University Of California Methods and treatments for the learning and memory deficits associated with Noonan syndrome
WO2017035733A1 (zh) * 2015-08-31 2017-03-09 深圳青雅启瑞生物科技有限公司 美金刚与牛蒡子苷元的缀合物及其组合物和用途
HUE055738T2 (hu) * 2017-10-17 2021-12-28 Atriva Therapeutics Gmbh Új MEK-inhibitor vírus- és baktérium-fertõzések kezelésére
EP3765087A1 (en) * 2018-04-13 2021-01-20 Healx Limited Kit, composition and combination therapy for fragile x syndrome
IL264854A (en) 2019-02-14 2020-08-31 Bahat Anat Spt5 inhibitors and methods of use thereof
WO2023196412A1 (en) * 2022-04-06 2023-10-12 Nobias Therapeutics, Inc. Liquid formulations comprising mitogen-activated protein kinase kinase (mek) inhibitors and methods using same
GB202415499D0 (en) * 2024-10-21 2024-12-04 Edvince Ab Novel compositions

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US6063383A (en) 1999-01-28 2000-05-16 Hsu; Wu-Ching Pharmaceutical suppository composites for fever and influenza and method of producing the composites
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Publication number Publication date
EP2600862A2 (en) 2013-06-12
CA2807510A1 (en) 2012-02-09
CN103221043A (zh) 2013-07-24
KR20130113430A (ko) 2013-10-15
US20150141380A1 (en) 2015-05-21
AU2011285611B2 (en) 2014-10-02
EP2600862A4 (en) 2014-01-22
EP2600862B1 (en) 2016-04-20
WO2012019113A2 (en) 2012-02-09
CN103221043B (zh) 2016-04-06
AU2011285611A1 (en) 2013-03-14
WO2012019113A3 (en) 2012-08-09

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