JP2001512459A - Ampaレセプタの活性を高めるベンゾフラザン化合物 - Google Patents
Ampaレセプタの活性を高めるベンゾフラザン化合物Info
- Publication number
- JP2001512459A JP2001512459A JP53589698A JP53589698A JP2001512459A JP 2001512459 A JP2001512459 A JP 2001512459A JP 53589698 A JP53589698 A JP 53589698A JP 53589698 A JP53589698 A JP 53589698A JP 2001512459 A JP2001512459 A JP 2001512459A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- ylcarbonyl
- benzofurazan
- compound according
- crr
- 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
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- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- PWEBUXCTKOWPCW-UHFFFAOYSA-L squarate Chemical compound [O-]C1=C([O-])C(=O)C1=O PWEBUXCTKOWPCW-UHFFFAOYSA-L 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
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- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/14—Thiadiazoles; Hydrogenated thiadiazoles condensed with carbocyclic rings or ring 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- 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
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- C07D271/12—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.下記の構造を持つ化合物であって ここで R1は、酸素又は硫黄であり、 R2及びR3は、−N=、−CR=、−CX=から成る基から個別に選択された ものであり、 Mは、=N−又は=CR4−であり、R4及びR8は個別のR、又はMを環の頂 点2’に結合する1つの結合部分を形成し、その結合部分は単結合から成る基か ら選択される。その基は−CRR’−、−CR=CR’−、−C(O)−、−O −、−S(O)y−、−NR−、−N=であり、 R5及びR7は、−(CRR')n−、−C(O)−、−CR=CR’−、−CR =CX−、−CRX−、−CXX’−、−S−、−O−の基から個別に選択され 、 R6は、−(CRR')m−、−C(O)−、−CR=CR’−、−CRX−、 −CXX’−、−S−、−O−の基から選択され、 ここでX及びX’は、−Br、−Cl、−F、−CN、−NO2、−OR、− SR、−NRR’、−C(O)R、−CO2R、−CONRR’、の基から個別 に選択される。ここで個々のX基上のR又はR’、又は2つの隣の基X上のR又 はR’は、共に1つの環を形成し、 R及びR’は、(i)水素、(ii)C1−C6枝つき又は枝なしアルキルから個 々に選択され、それは未置換か次の1つ以上の官能基で置換される。ハロゲン、 ニ トロ、アルコキシ、ヒドロキシ、アルキルチオ、アミノ、ケト、アルデヒド、カ ルボン酸、カルボキシルエステル、又はカルボキシルアミド、ここで1つの炭素 又は隣の炭素上の2つのアルキル基は共に1つの環をつくり、(iii)アリルは 、未置換か次の1つ以上の官能基で置換される。ハロゲン、ニトロ、アルコキシ 、ヒドロキシ、アリロキシ、アルキルチオ、アミノ、ケト、アルデヒド、カルボ ン酸、カルボキシルエステル、又はカルボキシルアミド、 m及びpは個々に0又は1で、 n及びyは個々に0、1又は2である、ことを特徴とするベンゾフラン化合物 。 2.R及びR’が、個々に(i)水素及び(ii)C1−C6枝つき又は枝なしアル キルから選択され、それらは、ハロゲン、ニトロ、アルコキシ、ヒドロキシ、ア ルキルチオ、アミノ、ケト、アルデヒド、カルボン酸、カルボキシルエステル、 又はカルボキシルアミドの内の、1つ以上の官能基で未置換か置換され、ここで 1つの炭素又は隣の炭素上の2つのアルキル基が、共に1つの環をつくることを 特徴とする、請求項1に記載の化合物。 3.R2及びR3が、−CR−で、Mが=CR4−であることを特徴とする、請求 項1に記載の化合物。 4.pが0、R1が酸素、R4及びR8が水素であることを特徴とする、請求項3 に記載の化合物。 5.R5及びR7が、−(CRR')n−で、R6が−(CRR')m−であることを 特徴とする、請求項4に記載の化合物。 6.R及びR’が水素、m=n=1で、上記化合物が1−(ベンゾフラザン−5 −イルカルボニル)ピペリジンであることを特徴とする、請求項5に記載の化合 物。 7.pが0、R1が硫黄、R4、R8、R及びR’が水素、m=n=1で、上記化 合物が1−(ベンゾ−2,1,3−チアジアゾール−5−イルカルボニル)ピペ リジンであることを特徴とする、請求項3に記載の化合物。 8.R5が−CR=CX−、R6が−(CRR')m−、R7が−(CRR')n−、 mが0であることを特徴とする、請求項4に記載の化合物。 9.R及びR’が水素であることを特徴とする、請求項8に記載の化合物。 10.Xがフルオリンでnが1、上記化合物が1−(ベンゾフラザン−5−イル カルボニル)−4−フルオロ−1,2,3,6−テトラヒドロピリジンであるこ とを特徴とする、請求項9に記載の化合物。 11.R5が−CR=CR’−、R6が−(CRR')m−、R7が−(CRR')n −、及びmが0であることを特徴とする、請求項4に記載の化合物。 12.R及びR’が水素であることを特徴とする、請求項11に記載の化合物。 13.nが1、上記化合物が1−(ベンゾフラザン−5−イルカルボニル)−1 ,2,3,6−テトラヒドロピリジンであることを特徴とする、請求項12に記 載の化合物。 14.R5及びR7が、−(CRR')n−で、R6が−C(O)−、−CRX−、 −CXX’−、−O−又は−S−、であることを特徴とする、請求項4に記載の 化合物。 15.R6が−CXX’−、R及びR’が水素、nが1、Xがフルオリン、上記 化合物が1−(ベンゾフラザン−5−イルカルボニル)−4’,4’−ジフルオ ロピペリジンであることを特徴とする、請求項14に記載の化合物。 16.R6が−CRX’−、R及びR’が水素、nが1であることを特徴とする 、請求項14に記載の化合物。 17.上記化合物が1−(ベンゾフラザン−5−イルカルボニル)−4’−フル オロピペリジン、1−(ベンゾフラザン−5−イルカルボニル)−4’−シアノ ピリジン、及び1−(ベンゾフラザン−5−イルカルボニル)−4’−ヒドロキ シピペリジンから選択されることを特徴とする、請求項16に記載の化合物。 18.R6が−O−、−S−又は−C(O)−、nが1、及びR及びR’が水素 、上記化合物が4−(ベンゾフラザン−5−イルカルボニル)モルフォリン、4 −(ベンゾフラザン−5−イルカルボニル)チオモルフォリン、及び4−(ベン ゾフラザン−5−イルカルボニル)ピペリドンから選択されることを特徴とする 、請求項14に記載の化合物。 19.Mが=CR4−、ここでR4とR8がMを環頂点2’に結合する結合部分を 共に形成し、結合部分は単結合が−CRR’−、−CR=CR’−、−C(O) −、−O−、−S−、−NR−、又は−N=、であることを特徴とする、請求項 1に記載の化合物。 20.R2とR3が−CR=、であることを特徴とする、請求項19に記載の化合 物。 21.pが0、R1が酸素、R5及びR7が−(CRR')n−、及びR6が−(CR R')m−、であることを特徴とする、請求項20に記載の化合物。 22.nが1であることを特徴とする、請求項21に記載の化合物。 23.結合部分が−CRR’−、−O−、−S−、又は−N=、であることを 特徴とする、請求項21に記載の化合物。 24.結合部分が、−O−、であることを特徴とする、請求項23に記載の化合 物。 25.対象哺乳動物のAMPAレセプタ作用を高めるため、製薬上許容される基 剤であると、請求項1から24のいずれかに記載されていることを特徴とする化 合物の使用。 26.上記高揚が、グルタミン酸塩の不足状態や、興奮を示すシナプスの数や強 度又はAMPAレセプタの数の低下によって起こる記憶やその他の認識作用の悪 化を、軽減する効果があると、請求項25に記載されていることを特徴とする化 合物の使用。 27.上記高揚が、グルタミン酸塩の不足状態や、興奮を示す結合部の数や強度 又はAMPAレセプタの数の低下によって起こる皮質部/溝部の不均衡から引き 起こされる精神分裂症や精神分裂様挙動の取り扱いに効果があると、請求項25 に記載されていることを特徴とする化合物の使用。 28.上記高揚が、AMPAレセプタの作用に依存する挙動の認識を促進するの に効果があると、請求項25に記載されていることを特徴とする化合物の使用。 29.上記化合物が、請求項2から18のいずれかに従うと、請求項25に記載 されていることを特徴とする化合物の使用。 30.上記化合物が、下記の構成の基から選択されると、請求項26に記載され ていることを特徴とする化合物の使用。 a.1−(ベンゾフラザン−5−イルカルボニル)ピペリジン、 b.1−(ベンゾ−2,1,3−チアジアゾール−5−イルカルボニル)ピペリ ジン、 c.1−(ベンゾフラザン−5−イルカルボニル)−4−フルオロ−1,2,3 ,6−テトラヒドロピリジン、 d.1−(ベンゾフラザン−5−イルカルボニル)−4’−フルオロピペリジン 、 e.1−(ベンゾフラザン−5−イルカルボニル)−4’,4’−ジフルオロピ ペリジン、 f.1−(ベンゾフラザン−5−イルカルボニル)−4’−シアノピペリジン、 g.1−(ベンゾフラザン−5−イルカルボニル)−4’−ヒドロキシピペリジ ン、 h.4−(ベンゾフラザン−5−イルカルボニル)モルフォリン、 i.4−(ベンゾフラザン−5−イルカルボニル)チオモルフォリン、及び j.4−(ベンゾフラザン−5−イルカルボニル)−4−ピペリドン。
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US08/800,108 US6110935A (en) | 1997-02-13 | 1997-02-13 | Benzofurazan compounds for enhancing glutamatergic synaptic responses |
US08/800,108 | 1997-02-13 | ||
PCT/US1998/002713 WO1998035950A1 (en) | 1997-02-13 | 1998-02-13 | Benzofurazan compounds which enhance ampa receptor activity |
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JP2006516283A (ja) * | 2003-01-13 | 2006-06-29 | コーテックス ファーマシューティカルズ, インコーポレイテッド | 睡眠不足とストレスに起因する知覚衰退の処置方法 |
JP2010514838A (ja) * | 2007-01-03 | 2010-05-06 | コルテックス・ファーマシューティカルズ・インコーポレーテッド | グルタミン酸作動性シナプス応答を増強する3−置換−[1,2,3]−ベンゾトリアジノン化合物 |
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Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
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IN188837B (ja) | 1998-05-22 | 2002-11-09 | Torrent Pharmaceuticals Ltd | |
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WO2011109398A2 (en) | 2010-03-02 | 2011-09-09 | President And Fellows Of Harvard College | Methods and compositions for treatment of angelman syndrome and autism spectrum disorders |
US9700596B2 (en) | 2011-03-04 | 2017-07-11 | The Regents Of The University Of California | Locally released growth factors to mediate motor recovery after stroke |
CN102633731B (zh) * | 2012-03-13 | 2014-04-30 | 四川大学华西医院 | 6-喹喔啉甲酸酰胺化合物、制备方法和应用 |
KR101421032B1 (ko) * | 2012-12-28 | 2014-07-22 | 주식회사 레고켐 바이오사이언스 | (2-메틸-1-(3-메틸벤질)-1H-벤조[d]이미다졸-5일)(피페리딘-5-일)메탄온의 제조방법 |
CN105579575A (zh) | 2013-06-13 | 2016-05-11 | 维罗技术有限责任公司 | 用于治疗代谢失调的组合物和方法 |
CN107286114B (zh) * | 2016-04-13 | 2020-08-18 | 中国人民解放军军事医学科学院毒物药物研究所 | Ampa受体增效剂的脑靶向前药及其医药用途 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3981864A (en) * | 1973-09-08 | 1976-09-21 | Eisai Co., Ltd. | 1,3-Benzodioxol derivatives |
FR2499991A1 (fr) * | 1981-02-19 | 1982-08-20 | Sandoz Sa | Nouveaux 2,1,3-benzothiadiazoles et 2,1,3-benzoxadiazoles, leur preparation et leur application comme medicaments |
US4420485A (en) * | 1982-09-29 | 1983-12-13 | Hoechst-Roussel Pharmaceuticals Inc. | 1'-[3-(1,2-Benzisoxazol-3-yl) proply]spiro[benzofuran-2(3H),3' or 4'-piperidines or 3'-pyrrolidines] |
US5112824A (en) * | 1989-12-08 | 1992-05-12 | Merck & Co., Inc. | Benzofuran compounds as class III antiarrhythmic agents |
US5032604A (en) * | 1989-12-08 | 1991-07-16 | Merck & Co., Inc. | Class III antiarrhythmic agents |
IL96507A0 (en) * | 1989-12-08 | 1991-08-16 | Merck & Co Inc | Nitrogen-containing spirocycles and pharmaceutical compositions containing them |
CA2450801C (en) * | 1992-07-24 | 2009-11-17 | The Regent Of The University Of California | Drugs that enhance synaptic responses mediated by ampa receptors |
DK0709384T3 (da) * | 1994-10-31 | 1999-08-23 | Merck Patent Gmbh | Benzylpiperidinderivater med høj affinitet til aminosyrereceptorers bindingssteder |
US5650409A (en) * | 1995-06-02 | 1997-07-22 | Cortex Pharmaceuticals, Inc. | Benzoyl piperidines/pyrrolidines for enhancing synaptic response |
US5736543A (en) * | 1996-04-03 | 1998-04-07 | The Regents Of The University Of California | Benzoxazines for enhancing synaptic response |
US5985871A (en) | 1997-12-24 | 1999-11-16 | Cortex Pharmaceuticals, Inc. | Benzoxazine compounds for enhancing synaptic response |
-
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JP2006516283A (ja) * | 2003-01-13 | 2006-06-29 | コーテックス ファーマシューティカルズ, インコーポレイテッド | 睡眠不足とストレスに起因する知覚衰退の処置方法 |
JP2010514838A (ja) * | 2007-01-03 | 2010-05-06 | コルテックス・ファーマシューティカルズ・インコーポレーテッド | グルタミン酸作動性シナプス応答を増強する3−置換−[1,2,3]−ベンゾトリアジノン化合物 |
JP2010535858A (ja) * | 2007-08-10 | 2010-11-25 | コーテックス ファーマシューティカルズ, インコーポレイテッド | グルタミン酸作動性シナプス反応を増大するための二環式アミド |
JP2012516845A (ja) * | 2009-02-02 | 2012-07-26 | コーテックス ファーマシューティカルズ, インコーポレイテッド | グルタミン酸作動性シナプス反応を増強するための二環式アミド誘導体 |
JP2013523892A (ja) * | 2010-04-15 | 2013-06-17 | アラーガン インコーポレイテッド | 視覚障害を処置するための組成物および方法 |
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