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 PDFInfo
- 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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- ES
- Spain
- Prior art keywords
- amino
- hydroxyethoxy
- carboxamide
- fluoro
- chloro
- Prior art date
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Classifications
-
- 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
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
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)
-
imagen1
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 (6)
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 |
CN108024990B (zh) * | 2015-08-31 | 2020-08-11 | 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 |
LT3697405T (lt) * | 2017-10-17 | 2021-10-25 | Atriva Therapeutics Gmbh | Naujas mek inhibitorius virusinėms ir bakterinėms infekcijoms gydyti |
CA3096759A1 (en) * | 2018-04-13 | 2019-10-17 | 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 |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5525625A (en) | 1995-01-24 | 1996-06-11 | Warner-Lambert Company | 2-(2-Amino-3-methoxyphenyl)-4-oxo-4H-[1]benzopyran for treating proliferative disorders |
US6512010B1 (en) | 1996-07-15 | 2003-01-28 | Alza Corporation | Formulations for the administration of fluoxetine |
US6821963B2 (en) | 1997-07-01 | 2004-11-23 | Warner-Lambert Company | 4-Bromo or 4-iodo phenylamino benzhydroxamic acid derivatives and their use as MEK inhibitors |
US6573044B1 (en) | 1997-08-07 | 2003-06-03 | The Regents Of The University Of California | Methods of using chemical libraries to search for new kinase inhibitors |
US6319955B1 (en) | 1998-01-06 | 2001-11-20 | The General Hospital Corporation | Use of MEK1 inhibitors as protective agents against damage due to ischemia |
US6150401A (en) | 1998-01-06 | 2000-11-21 | The General Hospital Corporation | Use of MEK1 inhibitors as protective agents against damage due to ischemia |
IT1299195B1 (it) | 1998-06-25 | 2000-02-29 | Sigma Tau Healthscience Spa | Composizione ad attivita' neuroprotettiva per la prevenzione ed il trattamento delle alterazioni nervose e comportamentali legate a stati |
US6147107A (en) | 1998-12-20 | 2000-11-14 | Virginia Commonwealth University | Specific inhibition of the P42/44 mitogen activated protein (map) kinase cascade sensitizes tumor cells |
US6696440B1 (en) | 1999-01-07 | 2004-02-24 | Warner-Lambert Company | Treatment of asthma with MEK inhibitors |
US6063383A (en) | 1999-01-28 | 2000-05-16 | Hsu; Wu-Ching | Pharmaceutical suppository composites for fever and influenza and method of producing the composites |
US6703420B1 (en) | 1999-03-19 | 2004-03-09 | Bristol-Myers Squibb Pharma Company | Amino-thio-acrylonitriles as MEK inhibitors |
AU2001236720A1 (en) | 2000-02-05 | 2001-08-14 | Bemis, Guy | Compositions useful as inhibitors of erk |
AU782878B2 (en) | 2000-02-05 | 2005-09-08 | Vertex Pharmaceuticals Incorporated | Pyrazole compositions useful as inhibitors of erk |
DE10017480A1 (de) | 2000-04-07 | 2001-10-11 | Transmit Technologietransfer | Verwendung von Substanzen, die als MEK Inhibitor wirken, zur Herstellung eines Arneimittels gegen DNA- und RNA-Viren |
WO2002002097A2 (en) * | 2000-06-30 | 2002-01-10 | Sweatt J David | Methods for treating seizure disorders by inhibiting mapk pathway activation with nitriles |
AU2001290940A1 (en) | 2000-09-15 | 2002-03-26 | Vertex Pharmaceuticals Incorporated | Isoxazoles and their use as inhibitors of erk |
IL149462A0 (en) | 2001-05-09 | 2002-11-10 | Warner Lambert Co | Method of treating or inhibiting neutrophil chemotaxis by administering a mek inhibitor |
WO2003039536A1 (en) | 2001-11-07 | 2003-05-15 | Yale University | Enhancement of taxane-based chemotherapy by a cdk1 antagonist |
EP1472206A1 (en) | 2002-02-05 | 2004-11-03 | Hormos Medical Corporation | Lignan derivatives |
US7235537B2 (en) | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
TWI343377B (en) | 2002-03-13 | 2011-06-11 | Array Biopharma Inc | N3 alkylated benzimidazole derivatives as mek inhibitors |
TW200520745A (en) * | 2003-09-19 | 2005-07-01 | Chugai Pharmaceutical Co Ltd | Novel 4-phenylamino-benzaldoxime derivatives and uses thereof as mitogen-activated protein kinase kinase (MEK) inhibitors |
US7732616B2 (en) | 2003-11-19 | 2010-06-08 | Array Biopharma Inc. | Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof |
US7517994B2 (en) | 2003-11-19 | 2009-04-14 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
TWI361066B (en) * | 2004-07-26 | 2012-04-01 | Chugai Pharmaceutical Co Ltd | 5-substituted-2-phenylamino benzamides as mek inhibitors |
WO2006134469A1 (en) * | 2005-06-14 | 2006-12-21 | Warner-Lambert Company Llc | Methods of preparing mek inhibitor |
AU2007299726A1 (en) * | 2006-09-22 | 2008-03-27 | Braincells, Inc. | Combination comprising an HMG-COA reductase inhibitor and a second neurogenic agent for treating a nervous system disorder and increasing neurogenesis |
EP2461682A4 (en) * | 2009-08-03 | 2013-03-06 | Theta Biomedical Consulting & Dev Co Inc | METHOD FOR TREATING AUTISTICAL DISEASES AND COMPOSITIONS THEREFOR |
-
2011
- 2011-08-05 EP EP11815379.0A patent/EP2600862B1/en not_active Not-in-force
- 2011-08-05 CA CA2807510A patent/CA2807510A1/en not_active Abandoned
- 2011-08-05 CN CN201180043887.7A patent/CN103221043B/zh not_active Expired - Fee Related
- 2011-08-05 WO PCT/US2011/046773 patent/WO2012019113A2/en active Application Filing
- 2011-08-05 ES ES11815379.0T patent/ES2575995T3/es active Active
- 2011-08-05 US US13/814,393 patent/US20150141380A1/en not_active Abandoned
- 2011-08-05 KR KR1020137005737A patent/KR20130113430A/ko not_active Application Discontinuation
- 2011-08-05 AU AU2011285611A patent/AU2011285611B2/en not_active Ceased
Also Published As
Publication number | Publication date |
---|---|
EP2600862A2 (en) | 2013-06-12 |
EP2600862A4 (en) | 2014-01-22 |
EP2600862B1 (en) | 2016-04-20 |
AU2011285611B2 (en) | 2014-10-02 |
WO2012019113A2 (en) | 2012-02-09 |
US20150141380A1 (en) | 2015-05-21 |
AU2011285611A1 (en) | 2013-03-14 |
KR20130113430A (ko) | 2013-10-15 |
WO2012019113A3 (en) | 2012-08-09 |
CN103221043A (zh) | 2013-07-24 |
CN103221043B (zh) | 2016-04-06 |
CA2807510A1 (en) | 2012-02-09 |
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