RU2012139491A - Бензизоксазолы и азабензизоксазолы как аллостерические потенциаторы mglur4, композиции и способы лечения неврологических дисфункций - Google Patents
Бензизоксазолы и азабензизоксазолы как аллостерические потенциаторы mglur4, композиции и способы лечения неврологических дисфункций Download PDFInfo
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- RU2012139491A RU2012139491A RU2012139491/04A RU2012139491A RU2012139491A RU 2012139491 A RU2012139491 A RU 2012139491A RU 2012139491/04 A RU2012139491/04 A RU 2012139491/04A RU 2012139491 A RU2012139491 A RU 2012139491A RU 2012139491 A RU2012139491 A RU 2012139491A
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- Prior art keywords
- alkyl
- group
- halogen
- optionally substituted
- membered ring
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- 238000000034 method Methods 0.000 title claims 20
- 239000000203 mixture Substances 0.000 title claims 17
- 102100038354 Metabotropic glutamate receptor 4 Human genes 0.000 title claims 8
- 101150025480 Grm4 gene Proteins 0.000 title 1
- 230000003281 allosteric effect Effects 0.000 title 1
- 150000008316 benzisoxazoles Chemical class 0.000 title 1
- 230000009251 neurologic dysfunction Effects 0.000 title 1
- 208000015015 neurological dysfunction Diseases 0.000 title 1
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 78
- 229910052717 sulfur Inorganic materials 0.000 claims abstract 73
- 229910052799 carbon Inorganic materials 0.000 claims abstract 67
- 229910052736 halogen Inorganic materials 0.000 claims abstract 57
- 150000002367 halogens Chemical group 0.000 claims abstract 57
- 150000001875 compounds Chemical class 0.000 claims abstract 48
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 42
- 239000001257 hydrogen Substances 0.000 claims abstract 42
- 150000002431 hydrogen Chemical group 0.000 claims abstract 39
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 39
- 125000003118 aryl group Chemical group 0.000 claims abstract 32
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract 32
- 125000000217 alkyl group Chemical group 0.000 claims 74
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 29
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims 18
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 18
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 17
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 17
- 230000004064 dysfunction Effects 0.000 claims 13
- 241000124008 Mammalia Species 0.000 claims 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 7
- 230000000694 effects Effects 0.000 claims 7
- 108010038422 metabotropic glutamate receptor 4 Proteins 0.000 claims 7
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 6
- 208000035475 disorder Diseases 0.000 claims 5
- 239000003814 drug Substances 0.000 claims 4
- 201000000980 schizophrenia Diseases 0.000 claims 4
- 208000019901 Anxiety disease Diseases 0.000 claims 3
- 208000018737 Parkinson disease Diseases 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 230000005062 synaptic transmission Effects 0.000 claims 3
- 208000031091 Amnestic disease Diseases 0.000 claims 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims 2
- 208000020925 Bipolar disease Diseases 0.000 claims 2
- 208000028698 Cognitive impairment Diseases 0.000 claims 2
- 206010012218 Delirium Diseases 0.000 claims 2
- 208000002720 Malnutrition Diseases 0.000 claims 2
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 claims 2
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 claims 2
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims 2
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims 2
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 claims 2
- 208000008589 Obesity Diseases 0.000 claims 2
- 208000028017 Psychotic disease Diseases 0.000 claims 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims 2
- 208000010877 cognitive disease Diseases 0.000 claims 2
- 229950006137 dexfosfoserine Drugs 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims 2
- 230000001071 malnutrition Effects 0.000 claims 2
- 235000000824 malnutrition Nutrition 0.000 claims 2
- 208000015380 nutritional deficiency disease Diseases 0.000 claims 2
- 235000020824 obesity Nutrition 0.000 claims 2
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 claims 2
- 230000003389 potentiating effect Effects 0.000 claims 2
- 206010061218 Inflammation Diseases 0.000 claims 1
- 208000000172 Medulloblastoma Diseases 0.000 claims 1
- 208000016285 Movement disease Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 230000036506 anxiety Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 230000004069 differentiation Effects 0.000 claims 1
- 239000006274 endogenous ligand Substances 0.000 claims 1
- 206010015037 epilepsy Diseases 0.000 claims 1
- 235000019441 ethanol Nutrition 0.000 claims 1
- 229930195712 glutamate Natural products 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 208000030159 metabolic disease Diseases 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 230000001272 neurogenic effect Effects 0.000 claims 1
- 210000002569 neuron Anatomy 0.000 claims 1
- 239000002858 neurotransmitter agent Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 235000019613 sensory perceptions of taste Nutrition 0.000 claims 1
- 230000004083 survival effect Effects 0.000 claims 1
- 230000024587 synaptic transmission, glutamatergic Effects 0.000 claims 1
- 230000035923 taste sensation Effects 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 0 N=*c1n[o]c2c1nccc2 Chemical compound N=*c1n[o]c2c1nccc2 0.000 description 7
- AFQIIKMZWPERMA-UHFFFAOYSA-N CCCC(NC)NCC Chemical compound CCCC(NC)NCC AFQIIKMZWPERMA-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
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- 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
- A61K31/42—Oxazoles
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- 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
- A61K31/42—Oxazoles
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- A61K31/42—Oxazoles
- A61K31/424—Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
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- 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
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- A61K31/4355—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
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- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Psychology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Measuring And Recording Apparatus For Diagnosis (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30348110P | 2010-02-11 | 2010-02-11 | |
| US61/303,481 | 2010-02-11 | ||
| PCT/US2011/024627 WO2011100614A1 (en) | 2010-02-11 | 2011-02-11 | BENZISOXAZOLES AND AZABENZISOXAZOLES AS mgluR4 ALLOSTERIC POTENTIATORS, COMPOSITIONS, AND METHODS OF TREATING NEUROLOGICAL DYSFUNCTION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2012139491A true RU2012139491A (ru) | 2014-03-20 |
Family
ID=44368169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2012139491/04A RU2012139491A (ru) | 2010-02-11 | 2011-02-11 | Бензизоксазолы и азабензизоксазолы как аллостерические потенциаторы mglur4, композиции и способы лечения неврологических дисфункций |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8916584B2 (enExample) |
| EP (1) | EP2533642A4 (enExample) |
| JP (1) | JP2013519685A (enExample) |
| KR (1) | KR20120120416A (enExample) |
| CN (1) | CN102834009A (enExample) |
| AU (1) | AU2011215645A1 (enExample) |
| BR (1) | BR112012020271A2 (enExample) |
| CA (1) | CA2789434A1 (enExample) |
| IL (1) | IL221389A0 (enExample) |
| MX (1) | MX2012009377A (enExample) |
| RU (1) | RU2012139491A (enExample) |
| SG (1) | SG183261A1 (enExample) |
| WO (1) | WO2011100614A1 (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2010208176A1 (en) | 2009-01-28 | 2011-09-15 | 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 |
| EP2771346A4 (en) | 2011-10-25 | 2015-06-03 | Merck Sharp & Dohme | ISOXAZOLOPYRIDIN-orexin |
| WO2013088315A1 (en) | 2011-12-15 | 2013-06-20 | Pfizer Limited | Sulfonamide derivatives |
| EA029352B1 (ru) * | 2013-09-25 | 2018-03-30 | Ф. Хоффманн-Ля Рош Аг | Производные этинила |
| KR101532211B1 (ko) * | 2014-04-30 | 2015-06-30 | 세종대학교산학협력단 | Ampk 억제기능에 기반한 뇌졸중 치료용 약학적 조성물 및 방법 |
| KR102746352B1 (ko) * | 2014-08-13 | 2024-12-24 | 오클랜드 유니서비시즈 리미티드 | 트립토판 디옥시게나제 (ido1 및 tdo)의 억제제 및 치료에서 이들의 용도 |
| 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 |
| WO2016115282A1 (en) * | 2015-01-13 | 2016-07-21 | Vanderbilt University | Benzoisoxazole-substituted compounds as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction |
| WO2016123629A1 (en) | 2015-01-30 | 2016-08-04 | Vanderbilt University | Indazole and azaindazole substituted compounds as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction |
| US10227343B2 (en) | 2015-01-30 | 2019-03-12 | Vanderbilt University | Isoquiniline and napthalene-substituted compounds as mGluR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction |
| WO2016179351A1 (en) | 2015-05-05 | 2016-11-10 | Northwestern University | Treatment of levodopa-induced dyskinesias |
| CN104926745A (zh) * | 2015-07-14 | 2015-09-23 | 佛山市赛维斯医药科技有限公司 | 含苯并异恶唑和末端卤代苄基类结构的化合物及其用途 |
| CN104974103A (zh) * | 2015-07-14 | 2015-10-14 | 佛山市赛维斯医药科技有限公司 | 一类含苯并异恶唑和烷氧苯基类结构的化合物及其用途 |
| CA2996681C (en) | 2015-08-27 | 2024-04-09 | Auckland Uniservices Limited | Inhibitors of tryptophan dioxygenases (ido1 and tdo) and their use in therapy |
| 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 |
| US10968227B2 (en) | 2016-11-08 | 2021-04-06 | Vanderbilt University | Isoquinoline ether 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 |
| WO2019006157A1 (en) | 2017-06-28 | 2019-01-03 | Vanderbilt University | Pyridine quinoline compounds as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction |
| US11427573B2 (en) | 2017-08-16 | 2022-08-30 | Vanderbilt University | Indazole compounds as MGLUR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction |
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| US20080194557A1 (en) * | 2007-01-18 | 2008-08-14 | Joseph Barbosa | Methods and compositions for the treatment of pain, inflammation and cancer |
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| CA2677843A1 (en) * | 2007-02-20 | 2008-08-28 | Novartis Ag | Macrocyclic compounds as hcv ns3 protease inhibitors |
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- 2011-02-11 EP EP11742914.2A patent/EP2533642A4/en not_active Withdrawn
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| WO2011100614A1 (en) | 2011-08-18 |
| EP2533642A4 (en) | 2013-08-07 |
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| CA2789434A1 (en) | 2011-08-18 |
| US8916584B2 (en) | 2014-12-23 |
| BR112012020271A2 (pt) | 2017-08-29 |
| SG183261A1 (en) | 2012-09-27 |
| JP2013519685A (ja) | 2013-05-30 |
| IL221389A0 (en) | 2012-10-31 |
| KR20120120416A (ko) | 2012-11-01 |
| EP2533642A1 (en) | 2012-12-19 |
| MX2012009377A (es) | 2012-09-12 |
| AU2011215645A1 (en) | 2012-09-20 |
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