JPWO2014162737A1 - タウ凝集阻害剤 - Google Patents
タウ凝集阻害剤 Download PDFInfo
- Publication number
- JPWO2014162737A1 JPWO2014162737A1 JP2015509918A JP2015509918A JPWO2014162737A1 JP WO2014162737 A1 JPWO2014162737 A1 JP WO2014162737A1 JP 2015509918 A JP2015509918 A JP 2015509918A JP 2015509918 A JP2015509918 A JP 2015509918A JP WO2014162737 A1 JPWO2014162737 A1 JP WO2014162737A1
- Authority
- JP
- Japan
- Prior art keywords
- catechol
- group
- tau
- aggregation inhibitor
- tau aggregation
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
- 229940122777 Tau aggregation inhibitor Drugs 0.000 title claims abstract description 31
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical group OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims abstract description 98
- -1 catechol structure compound Chemical class 0.000 claims abstract description 79
- KDHUXRBROABJBC-UHFFFAOYSA-N 4-Aminocatechol Chemical compound NC1=CC=C(O)C(O)=C1 KDHUXRBROABJBC-UHFFFAOYSA-N 0.000 claims abstract description 31
- GGNQRNBDZQJCCN-UHFFFAOYSA-N benzene-1,2,4-triol Chemical compound OC1=CC=C(O)C(O)=C1 GGNQRNBDZQJCCN-UHFFFAOYSA-N 0.000 claims abstract description 24
- 125000001424 substituent group Chemical group 0.000 claims abstract description 22
- 230000002776 aggregation Effects 0.000 claims abstract description 17
- 238000004220 aggregation Methods 0.000 claims abstract description 17
- 208000034799 Tauopathies Diseases 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 6
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims abstract description 6
- 201000011240 Frontotemporal dementia Diseases 0.000 claims abstract description 4
- 201000010374 Down Syndrome Diseases 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 53
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000003277 amino group Chemical group 0.000 claims description 15
- IXWOUPGDGMCKGT-UHFFFAOYSA-N 2,3-dihydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1O IXWOUPGDGMCKGT-UHFFFAOYSA-N 0.000 claims description 12
- LPYUENQFPVNPHY-UHFFFAOYSA-N 3-methoxycatechol Chemical compound COC1=CC=CC(O)=C1O LPYUENQFPVNPHY-UHFFFAOYSA-N 0.000 claims description 10
- JXZABYGWFNGNLB-UHFFFAOYSA-N 4-methoxybenzene-1,2-diol Chemical compound COC1=CC=C(O)C(O)=C1 JXZABYGWFNGNLB-UHFFFAOYSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- WWOBYPKUYODHDG-UHFFFAOYSA-N 4-chlorocatechol Chemical compound OC1=CC=C(Cl)C=C1O WWOBYPKUYODHDG-UHFFFAOYSA-N 0.000 claims description 6
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- MGBKJKDRMRAZKC-UHFFFAOYSA-N 3-aminobenzene-1,2-diol Chemical compound NC1=CC=CC(O)=C1O MGBKJKDRMRAZKC-UHFFFAOYSA-N 0.000 claims description 5
- XESZUVZBAMCAEJ-UHFFFAOYSA-N 4-tert-butylcatechol Chemical compound CC(C)(C)C1=CC=C(O)C(O)=C1 XESZUVZBAMCAEJ-UHFFFAOYSA-N 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
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- SZIQALHLPUTBOS-UHFFFAOYSA-N 4-(1-hydroxy-2-morpholin-4-ylethyl)benzene-1,2-diol Chemical compound C=1C=C(O)C(O)=CC=1C(O)CN1CCOCC1 SZIQALHLPUTBOS-UHFFFAOYSA-N 0.000 claims description 4
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- 238000010172 mouse model Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002791 naphthoquinones Chemical class 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000007658 neurological function Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000001725 pyrenyl group Chemical group 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- CQRYARSYNCAZFO-UHFFFAOYSA-N salicyl alcohol Chemical compound OCC1=CC=CC=C1O CQRYARSYNCAZFO-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940048098 sodium sarcosinate Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000012134 supernatant fraction Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000007470 synaptic degeneration Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000003960 triphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C3=CC=CC=C3C12)* 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- 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
- A61K31/05—Phenols
-
- 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
- A61K31/05—Phenols
- A61K31/055—Phenols the aromatic ring being substituted by halogen
-
- 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
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
-
- 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
- A61K31/11—Aldehydes
-
- 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
- A61K31/12—Ketones
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (13)
- カテコール、
炭化水素基を除く、電子供与性の置換基Rを、カテコール環の4位に有する4位置換カテコール構造化合物、若しくは
電子供与性の置換基Rを、カテコール環の3位に有する3位置換カテコール構造化合物、
又はこれらの塩を含む、
タウオパチーの予防及び/又は治療に用いられるタウ凝集阻害剤。 - 前記4位置換カテコール構造化合物は、アミノ基、水酸基、アルコキシ基又はチオール基の何れかからなる置換基Rを、カテコール環の4位に有するものである請求項1記載のタウ凝集阻害剤。
- 前記4位置換カテコール構造化合物は、4-アミノカテコールである請求項2記載のタウ凝集阻害剤。
- 前記4位置換カテコール構造化合物は、1,2,4-ベンゼントリオールである請求項2記載のタウ凝集阻害剤。
- 前記4位置換カテコール構造化合物は、
4-(イソペンチルアミノ)カテコール、又は、
4-メトキシカテコールであることを特徴とする請求項2記載のタウ凝集阻害剤。 - 前記4位置換カテコール構造化合物は、
4-(4-アミノブタノイルアミノ)カテコール、
4-(モルホリノカルボニルアミノ)カテコール、又は、
4-(ジイソペンチルアミノ)カテコール
であることを特徴とする請求項1記載のタウ凝集阻害剤。 - 前記3位置換カテコール構造化合物は、アミノ基、水酸基、アルコキシ基又はチオール基の何れかからなる置換基Rを、カテコール環の3位に有するものである請求項1記載のタウ凝集阻害剤。
- 前記3位置換カテコール構造含有化合物は、3-メトキシカテコールである請求項7記載のタウ凝集阻害剤。
- 前記3位置換カテコール構造含有化合物は、ピロガロールである請求項7記載のタウ凝集阻害剤。
- 前記3位置換カテコール構造含有化合物は、3-アミノカテコールである請求項7記載のタウ凝集阻害剤。
- 2,3-ジヒドロキシベンズアルデヒド、4-tert-ブチルカテコール、3,4-ジヒドロベンジルアミン、4-クロロアセチルカテコール、1-(3,4-ジヒドロキシフェニル)-2-モルホリノエタノール、及び、4-クロロカテコールからなる群から選ばれたカテコール構造含有化合物又はその塩を含む、タウオパチーの予防及び/又は治療に用いられるタウ凝集阻害剤。
- 前記タウオパチーは、AD、ダウン症、前頭側頭型認知症、皮質基底核変性症(CBD)、又は進行性核上性麻痺(PSP)である請求項1乃至11の何れか1項に記載のタウ凝集阻害剤。
- 更に製薬上許容される等張化剤、緩衝剤、溶解補助剤、防腐剤、及びpH調整剤から選択される1又はそれ以上の添加剤を含有する請求項1乃至12の何れか1項に記載のタウ凝集阻害剤。
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JP2013076614 | 2013-04-02 | ||
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PCT/JP2014/001919 WO2014162737A1 (ja) | 2013-04-02 | 2014-04-02 | タウ凝集阻害剤 |
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US (1) | US9907799B2 (ja) |
EP (1) | EP2962687B1 (ja) |
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Citations (3)
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JP2003532634A (ja) * | 1999-12-30 | 2003-11-05 | プロテオテック・インコーポレイテッド | アミロイド症およびα−シヌクレイン線維疾患の処置用ポリヒドロキシル化芳香族化合物 |
WO2009003147A1 (en) * | 2007-06-26 | 2008-12-31 | Parkinson's Institute | Methods and compositions for the treatment of neurological disorders |
JP2012508740A (ja) * | 2008-11-14 | 2012-04-12 | パーキンソンズ インスティテュート | 変性α−シヌクレイン機能の治療のための組成物および方法 |
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GB1144905A (en) | 1965-03-25 | 1969-03-12 | Fisons Pharmaceuticals Ltd | Substituted bis-(2-carboxy-chromonyl-oxy) derivatives and preparation and pharmaceutical compositions thereof |
JPS62106015A (ja) | 1985-10-31 | 1987-05-16 | Sumitomo Pharmaceut Co Ltd | 抗痴呆薬 |
AU2001253597A1 (en) | 2000-04-12 | 2001-10-30 | Minerva Biotechnologies Corporation | Treatment of neurodegenerative disease |
AU2002243451A1 (en) | 2001-01-02 | 2002-07-16 | Sention, Inc. | Use of catecholamine reuptake inhibitors to enhance memory |
GB0117326D0 (en) | 2001-07-16 | 2001-09-05 | Univ Aberdeen | Napthoquinone-type inhibitors of protein aggregation |
JP2005505548A (ja) | 2001-08-29 | 2005-02-24 | ユクロ ヨーロピアン コントラクト リサーチ ゲーエムベーハー ウント コー.カーゲー | 神経細胞変性の病気の治療のためのβ−アドレナリン受容体拮抗薬を使用する方法 |
US20050009925A1 (en) | 2001-12-11 | 2005-01-13 | Bymaster Franklin Porter | Use of norepinephrine reuptake inhibitors for the treatment of cognitive failure |
US8455687B2 (en) * | 2002-05-31 | 2013-06-04 | Proteotech, Inc. | Compounds and compositions for use as modulators of tau aggregation and alleviation of tauopathies |
US20110263696A1 (en) | 2007-03-30 | 2011-10-27 | Graves Donald J | Proanthocyanidins from cinnamon and its water soluble extract inhibit tau aggregation |
US8669048B2 (en) | 2008-06-24 | 2014-03-11 | Parkinson's Institute | Pluripotent cell lines and methods of use thereof |
WO2011071920A2 (en) | 2009-12-07 | 2011-06-16 | Board Of Regents, The University Of Texas System | Promoting cycling of apoe4 isoform |
US20140249180A1 (en) | 2011-10-03 | 2014-09-04 | National Center For Geriatrics And Gerontology | Tau aggregation inhibitor |
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2014
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- 2014-04-02 WO PCT/JP2014/001919 patent/WO2014162737A1/ja active Application Filing
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JP2003532634A (ja) * | 1999-12-30 | 2003-11-05 | プロテオテック・インコーポレイテッド | アミロイド症およびα−シヌクレイン線維疾患の処置用ポリヒドロキシル化芳香族化合物 |
WO2009003147A1 (en) * | 2007-06-26 | 2008-12-31 | Parkinson's Institute | Methods and compositions for the treatment of neurological disorders |
JP2012508740A (ja) * | 2008-11-14 | 2012-04-12 | パーキンソンズ インスティテュート | 変性α−シヌクレイン機能の治療のための組成物および方法 |
Non-Patent Citations (1)
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CAN.J.CHEM., vol. 90, JPN6017050950, 2012, pages 865 - 873, ISSN: 0003715291 * |
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EP2962687A4 (en) | 2016-09-28 |
US20160030437A1 (en) | 2016-02-04 |
WO2014162737A1 (ja) | 2014-10-09 |
EP2962687A1 (en) | 2016-01-06 |
EP2962687B1 (en) | 2019-06-05 |
US9907799B2 (en) | 2018-03-06 |
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