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MA38885A1 - Dérivés d'éthynyle modulateurs allosteriques positifs (pam) du recepteur metabotropique du glutamate 4 (mglu4) - Google Patents

Dérivés d'éthynyle modulateurs allosteriques positifs (pam) du recepteur metabotropique du glutamate 4 (mglu4)

Info

Publication number
MA38885A1
MA38885A1 MA38885A MA38885A MA38885A1 MA 38885 A1 MA38885 A1 MA 38885A1 MA 38885 A MA38885 A MA 38885A MA 38885 A MA38885 A MA 38885A MA 38885 A1 MA38885 A1 MA 38885A1
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MA
Morocco
Prior art keywords
group
atom
lower alkyl
halogen
substituted
Prior art date
Application number
MA38885A
Other languages
English (en)
Other versions
MA38885B1 (fr
Inventor
Eric Vieira
Georg Jaeschke
Antonio Ricci
Daniel Rueher
Barbara Biemans
Wolfgang Guba
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of MA38885A1 publication Critical patent/MA38885A1/fr
Publication of MA38885B1 publication Critical patent/MA38885B1/fr

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    • C07ORGANIC CHEMISTRY
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    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72Quinazolines; Hydrogenated quinazolines
    • C07D239/95Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
    • C07D239/96Two oxygen atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • A61P25/10Antiepileptics; Anticonvulsants for petit-mal
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • 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
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72Quinazolines; Hydrogenated quinazolines
    • C07D239/86Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88Oxygen atoms
    • C07D239/91Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/04Heterocyclic 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
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/10Heterocyclic 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 linked by a carbon chain containing aromatic rings
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    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D471/02Heterocyclic 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
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    • C07D487/02Heterocyclic 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
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    • C07ORGANIC CHEMISTRY
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    • C07D487/02Heterocyclic 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
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    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Psychiatry (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Psychology (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Epidemiology (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Thiazole And Isothizaole Compounds (AREA)

Abstract

La présente invention porte sur des composés de formule i dans laquelle y représente n ou c-r1' ; g représente un noyau aromatique ou hétéroaromatique à 5 ou 6 chaînons contenant 0, 1, 2 ou 3 hétéroatomes, choisi dans le groupe constitué par les noyaux phényle, pyridinyle à différentes positions de n, imidazolyle, pyrazinyle, pyrimidinyle, thiophényle, thiazolyle, pyrazolyle ou thiadiazolyle, qui sont éventuellement substitués par 1, 2 ou 3 substituants, choisis dans le groupe constitué par les substituants halogéno, alkyle inférieur, alcoxy inférieur, alcoxy inférieur substitué par halogène ou nrr' ; r et r' sont chacun indépendamment de l'autre l'atome d'hydrogène ou un groupe alkyle inférieur ou ils peuvent former conjointement avec l'atome n auquel ils sont attachés un groupe hétérocyclique saturé à cinq ou six chaînons qui peut contenir un atome d'oxygène ou groupe nh ou n-(alkyle inférieur) supplémentaire ; r1 représente l'atome d'hydrogène, un atome d'halogène ou un groupe alkyle inférieur substitué par halogène ; r1' représente l'atome d'hydrogène, un atome d'halogène ou un groupe alkyle inférieur substitué par halogène ; r2 représente l'atome d'hydrogène ou un groupe alkyle inférieur, alcoxyalkyle inférieur, cycloalkyle ou hétérocycloalkyle ; ou r2 peut former conjointement avec l'atome de carbone le plus proche dans un groupe g un groupe (ia), a représentant -ch2-, -ch2ch2 ou -c(ch3)2- ; r3 est un groupe phényle ou pyridinyle, l'atome n dans le groupe pyridinyle pouvant être en différentes positions ; ou sur un sel ou sel d'addition d'acide pharmaceutiquement acceptable de ceux-ci, sur un mélange racémique de ceux-ci ou sur son énantiomère et/ou isomère optique et/ou stéréoisomère correspondant. Il a été trouvé de manière inattendue que les composés de formule générale i sont des modulateurs allostériques positifs (pam) du récepteur métabotropique du glutamate 4 (mglu4), utiles pour le traitement de la maladie de parkinson, de l'anxiété, de vomissements, d'un trouble obsessionnel-compulsif, de l'autisme, pour la neuroprotection et pour le traitement d'un cancer, d'une dépression et du diabète de type 2.
MA38885A 2013-09-25 2014-09-22 Dérivés d'éthynyle modulateurs allosteriques positifs (pam) du recepteur metabotropique du glutamate 4 (mglu4) MA38885B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP13185856 2013-09-25
PCT/EP2014/070100 WO2015044075A1 (fr) 2013-09-25 2014-09-22 Dérivés d'éthynyle

Publications (2)

Publication Number Publication Date
MA38885A1 true MA38885A1 (fr) 2017-12-29
MA38885B1 MA38885B1 (fr) 2018-11-30

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Family Applications (1)

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MA38885A MA38885B1 (fr) 2013-09-25 2014-09-22 Dérivés d'éthynyle modulateurs allosteriques positifs (pam) du recepteur metabotropique du glutamate 4 (mglu4)

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Country Link
US (2) US20160207890A1 (fr)
EP (1) EP3049409B1 (fr)
JP (1) JP6134441B2 (fr)
KR (1) KR101757603B1 (fr)
CN (1) CN105579447B (fr)
AR (1) AR097721A1 (fr)
AU (1) AU2014327504B2 (fr)
BR (1) BR112016005994A2 (fr)
CA (1) CA2924376A1 (fr)
CL (1) CL2016000677A1 (fr)
CR (1) CR20160075A (fr)
DK (1) DK3049409T3 (fr)
EA (1) EA029352B1 (fr)
ES (1) ES2630319T3 (fr)
HU (1) HUE034849T2 (fr)
IL (1) IL244039B (fr)
MA (1) MA38885B1 (fr)
MX (1) MX370341B (fr)
MY (1) MY183953A (fr)
PE (1) PE20160666A1 (fr)
PH (1) PH12016500427A1 (fr)
PL (1) PL3049409T3 (fr)
SG (1) SG11201602029VA (fr)
SI (1) SI3049409T1 (fr)
TW (1) TWI527801B (fr)
UA (1) UA116277C2 (fr)
WO (1) WO2015044075A1 (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UA117855C2 (uk) * 2014-02-25 2018-10-10 Ф. Хоффманн-Ля Рош Аг Похідні етинілу
JP6539749B2 (ja) * 2015-03-19 2019-07-03 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft mGluR4のモジュレーターとしての3−(4−エチニルフェニル)ヘキサヒドロピリミジン−2,4−ジオン誘導体
HUE045145T2 (hu) 2015-07-15 2019-12-30 Hoffmann La Roche Etinil-származékok metabotróp glutamátreceptor-modulátorokként
AR105556A1 (es) 2015-08-03 2017-10-18 Hoffmann La Roche Derivados de etinilo
WO2017031116A1 (fr) * 2015-08-18 2017-02-23 The Arizona Board Of Regents On Behalf Of The University Of Arizona Inhibiteurs de ku70/80 à petites molécules et utilisations associées
JP6936305B2 (ja) 2016-07-18 2021-09-15 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft エチニル誘導体
CN112566906B (zh) 2018-07-26 2024-11-12 多曼治疗学公司 取代的喹唑啉酮衍生物和它们作为mglur4的正变构调节剂的用途

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10330359A (ja) * 1997-03-31 1998-12-15 Nippon Bayeragrochem Kk フエニルアセチレン誘導体及び除草剤
GB0503646D0 (en) * 2005-02-22 2005-03-30 Novartis Ag Organic compounds
NZ581817A (en) * 2007-06-03 2012-05-25 Univ Vanderbilt Benzamide mglur5 positive allosteric modulators and methods of making and using same
IN2012DN02580A (fr) * 2009-09-04 2015-08-28 Univ Vanderbilt
WO2011100614A1 (fr) * 2010-02-11 2011-08-18 Vanderbilt University Benzisoxazoles et azabenzisoxazoles en tant que potentialisateurs allostériques du sous-type 4 du récepteur du glutamate métabotropique (mglur4), compositions, et procédés de traitement de dysfonctionnements neurologiques
US8420661B2 (en) * 2010-04-13 2013-04-16 Hoffmann-La Roche Inc. Arylethynyl derivatives
EP2568809A4 (fr) * 2010-05-12 2013-11-06 Univ Vanderbilt Potentialisateurs allostériques hétérocycliques sulfonés du mglur4, compositions associées et méthodes de traitement d'un dysfonctionnement neurologique
UA110862C2 (uk) * 2011-10-07 2016-02-25 Ф. Хоффманн-Ля Рош Аг Похідні етинілу як алостеричні модулятори метаботропного рецептора глутамату mglur 5
CN102503888A (zh) * 2011-10-08 2012-06-20 西安交通大学 2-芳基-1,3-异喹啉二酮类抗肿瘤化合物及其合成方法和用途

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HK1220200A1 (zh) 2017-04-28
MX2016002717A (es) 2016-06-08
DK3049409T3 (en) 2017-07-10
IL244039B (en) 2019-06-30
CN105579447B (zh) 2018-11-13
CR20160075A (es) 2016-05-04
PE20160666A1 (es) 2016-07-09
MY183953A (en) 2021-03-17
SG11201602029VA (en) 2016-04-28
PL3049409T3 (pl) 2017-09-29
MX370341B (es) 2019-12-10
US9676732B2 (en) 2017-06-13
EP3049409B1 (fr) 2017-05-03
EA201690408A1 (ru) 2016-07-29
HUE034849T2 (en) 2018-03-28
UA116277C2 (uk) 2018-02-26
EA029352B1 (ru) 2018-03-30
AU2014327504A1 (en) 2016-02-18
JP6134441B2 (ja) 2017-05-24
TW201524963A (zh) 2015-07-01
EP3049409A1 (fr) 2016-08-03
WO2015044075A1 (fr) 2015-04-02
MA38885B1 (fr) 2018-11-30
KR20160044581A (ko) 2016-04-25
IL244039A0 (en) 2016-04-21
ES2630319T3 (es) 2017-08-21
AR097721A1 (es) 2016-04-13
KR101757603B1 (ko) 2017-07-12
TWI527801B (zh) 2016-04-01
AU2014327504B2 (en) 2018-01-04
JP2016531869A (ja) 2016-10-13
BR112016005994A2 (pt) 2017-08-01
CN105579447A (zh) 2016-05-11
CL2016000677A1 (es) 2016-11-04
SI3049409T1 (sl) 2017-08-31
CA2924376A1 (fr) 2015-04-02
US20170114028A1 (en) 2017-04-27
US20160207890A1 (en) 2016-07-21
PH12016500427A1 (en) 2016-05-16

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