WO2011057208A3 - Aryl and heteroaryl sulfones as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction - Google Patents

Aryl and heteroaryl sulfones as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction Download PDF

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Publication number
WO2011057208A3
WO2011057208A3 PCT/US2010/055861 US2010055861W WO2011057208A3 WO 2011057208 A3 WO2011057208 A3 WO 2011057208A3 US 2010055861 W US2010055861 W US 2010055861W WO 2011057208 A3 WO2011057208 A3 WO 2011057208A3
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WO
WIPO (PCT)
Prior art keywords
methods
compositions
aryl
treating neurological
compounds
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Application number
PCT/US2010/055861
Other languages
French (fr)
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WO2011057208A2 (en
Inventor
P. Jeffrey Conn
Craig W. Lindsley
Corey R. Hopkins
Charles David Weaver
Colleen M. Niswender
Yiu-Yin Cheung
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Vanderbilt University
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Publication date
Priority to BR112012010738A priority Critical patent/BR112012010738A2/en
Priority to MX2012005248A priority patent/MX2012005248A/en
Priority to AU2010314891A priority patent/AU2010314891A1/en
Priority to RU2012121631/15A priority patent/RU2012121631A/en
Priority to CN2010800589711A priority patent/CN103079570A/en
Priority to CA2780128A priority patent/CA2780128A1/en
Application filed by Vanderbilt University filed Critical Vanderbilt University
Priority to EP10829242A priority patent/EP2498781A2/en
Priority to US13/508,535 priority patent/US8912336B2/en
Priority to JP2012538064A priority patent/JP2013510178A/en
Publication of WO2011057208A2 publication Critical patent/WO2011057208A2/en
Priority to IL219568A priority patent/IL219568A0/en
Publication of WO2011057208A3 publication Critical patent/WO2011057208A3/en

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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
    • A61K31/41—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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Psychiatry (AREA)
  • Epidemiology (AREA)
  • Obesity (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Psychology (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Furan Compounds (AREA)
  • Pyridine Compounds (AREA)

Abstract

In one aspect, the invention relates to sulfone compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds, for example, in treating neurological and psychiatric disorders or other disease state associated with glutamate dysfunction.
PCT/US2010/055861 2009-11-06 2010-11-08 Aryl and heteroaryl sulfones as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction WO2011057208A2 (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
MX2012005248A MX2012005248A (en) 2009-11-06 2010-11-08 Aryl and heteroaryl sulfones as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction.
AU2010314891A AU2010314891A1 (en) 2009-11-06 2010-11-08 Aryl and heteroaryl sulfones as MGLUR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
RU2012121631/15A RU2012121631A (en) 2009-11-06 2010-11-08 Aryl and heteroaryl sulfones as allosteric potentiating agents for mGluR4, compositions and methods for treating neurological dysfunctions
CN2010800589711A CN103079570A (en) 2009-11-06 2010-11-08 Aryl and heteroaryl sulfones as MGLUR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
CA2780128A CA2780128A1 (en) 2009-11-06 2010-11-08 Aryl and heteroaryl sulfones as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
BR112012010738A BR112012010738A2 (en) 2009-11-06 2010-11-08 "Aryl and heteroaryl sulfones as allosteric mglur4 enhancers, compositions and methods of treating neurological dysfunction"
EP10829242A EP2498781A2 (en) 2009-11-06 2010-11-08 Aryl and heteroaryl sulfones as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
US13/508,535 US8912336B2 (en) 2009-11-06 2010-11-08 Aryl and heteroaryl sulfones as mGluR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
JP2012538064A JP2013510178A (en) 2009-11-06 2010-11-08 Aryl and heteroaryl sulfones as mGluR4 allosteric enhancers, compositions, and methods of treating neurological dysfunction
IL219568A IL219568A0 (en) 2009-11-06 2012-05-03 Aryl and heteroaryl sulfones, as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US25885609P 2009-11-06 2009-11-06
US61/258,856 2009-11-06

Publications (2)

Publication Number Publication Date
WO2011057208A2 WO2011057208A2 (en) 2011-05-12
WO2011057208A3 true WO2011057208A3 (en) 2014-03-20

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PCT/US2010/055861 WO2011057208A2 (en) 2009-11-06 2010-11-08 Aryl and heteroaryl sulfones as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction

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Country Link
US (1) US8912336B2 (en)
EP (1) EP2498781A2 (en)
JP (1) JP2013510178A (en)
KR (1) KR20120115252A (en)
CN (1) CN103079570A (en)
AU (1) AU2010314891A1 (en)
BR (1) BR112012010738A2 (en)
CA (1) CA2780128A1 (en)
IL (1) IL219568A0 (en)
MX (1) MX2012005248A (en)
RU (1) RU2012121631A (en)
WO (1) WO2011057208A2 (en)

Families Citing this family (16)

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CA2751176A1 (en) 2009-01-28 2010-08-05 Vanderbilt University Substituted 1,1,3,3-tetraoxidobenzo[d][1,3,2]dithiazoles as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
US8759377B2 (en) 2009-11-23 2014-06-24 Vanderbilt University Substituted dioxopiperidines and dioxopyrrolidines as MGLUR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
GB201104153D0 (en) 2011-03-11 2011-04-27 Glaxo Group Ltd Novel compounds
WO2016115272A1 (en) 2015-01-13 2016-07-21 Vanderbilt University Benzothiazole and benzisothiazole-substituted compounds as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
WO2016123627A1 (en) 2015-01-30 2016-08-04 Vanderbilt University Isoquiniline and napthalene-substituted compounds as mglur4 allosteric potentiators, compounds, and methods of treating neurological dysfunction
US10526323B2 (en) 2015-01-30 2020-01-07 Vanderbilt University Indazole and azaindazole substituted compounds as mGluR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
US9987242B2 (en) 2015-05-05 2018-06-05 Northwestern University Treatment of Levodopa-induced Dyskinesias
AR105556A1 (en) * 2015-08-03 2017-10-18 Hoffmann La Roche ETHYLENE DERIVATIVES
US10710997B2 (en) 2016-09-01 2020-07-14 Vanderbilt University Isoquinoline amide and isoquinoline amide-substituted compounds as mGluR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
US10294222B2 (en) 2016-09-01 2019-05-21 Vanderbilt University Benzomorpholine and benzomorpholine-substituted compounds as MGLUR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
WO2018089544A1 (en) 2016-11-08 2018-05-17 Vanderbilt University Isoquinoline amine compounds as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
WO2018089546A1 (en) 2016-11-08 2018-05-17 Vanderbilt University Isoquinoline ether compounds as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
CN108148054B (en) * 2016-12-05 2021-01-08 中国科学院大连化学物理研究所 Pyridyl bridged chiral oxazoline compound and synthetic method thereof
US11319304B2 (en) 2017-06-28 2022-05-03 Vanderbilt University Pyridine quinoline compounds as MGLUR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
SG11202001264UA (en) 2017-08-16 2020-03-30 Univ Vanderbilt Indazole compounds as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
CN112409251B (en) * 2020-11-26 2022-07-05 成都百泉生物医药科技有限公司 Omeprazole process impurity and preparation method thereof

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Publication number Publication date
RU2012121631A (en) 2013-12-20
CA2780128A1 (en) 2011-05-12
MX2012005248A (en) 2012-06-14
WO2011057208A2 (en) 2011-05-12
CN103079570A (en) 2013-05-01
JP2013510178A (en) 2013-03-21
KR20120115252A (en) 2012-10-17
US8912336B2 (en) 2014-12-16
BR112012010738A2 (en) 2019-09-24
EP2498781A2 (en) 2012-09-19
US20120245185A1 (en) 2012-09-27
IL219568A0 (en) 2012-06-28
AU2010314891A1 (en) 2012-06-07

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