JP2020517701A - 記憶および認知を改善する、ならびに記憶および認知障害を処置するための方法 - Google Patents
記憶および認知を改善する、ならびに記憶および認知障害を処置するための方法 Download PDFInfo
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- JP2020517701A JP2020517701A JP2019558399A JP2019558399A JP2020517701A JP 2020517701 A JP2020517701 A JP 2020517701A JP 2019558399 A JP2019558399 A JP 2019558399A JP 2019558399 A JP2019558399 A JP 2019558399A JP 2020517701 A JP2020517701 A JP 2020517701A
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- 229940124648 γ-Secretase Modulator Drugs 0.000 description 1
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Abstract
Description
本出願は、2017年4月26日出願の米国仮出願第62/490,377号の利益を主張する。先行出願の開示は、本出願の開示の一部とみなされる(参照により組み込まれる)。
本開示は、医薬化合物を投与することによる疾患の処置に関する。特に、本開示は、T型カルシウムチャネルアンタゴニストを投与することにより、記憶もしくは認知を改善するため、または記憶もしくは認知障害を処置するため、または疾患もしくは状態の認知症状を処置するための処置に関する。
T型カルシウムチャネルは膜脱分極の間に開口する低電圧活性化型カルシウムチャネルであり、活動電位または脱分極シグナル後に細胞へのカルシウム流入を媒介する。心筋および平滑筋内に存在することが知られているT型カルシウムチャネルは、更に、中枢神経系内の多くのニューロン細胞にも存在する。T型カルシウムチャネル(一過性開口型カルシウムチャネル)は、より陰性側の膜電位によって活性化される能力、それらの単一チャネルコンダクタンスの小ささ、および、L型カルシウムチャネルを標的とする従来のカルシウムチャネルアンタゴニスト薬に対するそれらの非反応性により、L型カルシウムチャネル(長時間作用性カルシウムチャネル)とは異なっている。
本開示は、T型カルシウムチャネルアンタゴニストを投与することにより、記憶もしくは認知を改善するため、または記憶もしくは認知障害を処置するため、または疾患もしくは状態の認知症状を処置するための処置に関する。方法は、かかる処置を必要とする対象に治療有効量のT型カルシウムチャネルアンタゴニストを投与することを含む。認知および/または記憶を改善する処置のためにT型カルシウムチャネルアンタゴニストを使用することも、提供される。本開示は、記憶を改善する処置のための医薬の製造におけるT型カルシウムチャネルアンタゴニストの使用も提供する。
本開示は、T型電位開口型カルシウムチャネルがドラベ症候群(すなわち、乳児重症ミオクロニー癲癇;SMEI)に関与していることを記載する。本開示は、かかるT型電位開口型カルシウムチャネルの調節がドラベ症候群の処置に有効でありうることを更に記載する。
特に定義されない限り、本明細書で用いられる全ての専門および科学用語は、本開示の属する分野の当業者によって一般的に理解されているのと同じ意味を有する。
本開示は、認知を改善する、記憶を改善する、認知障害を処置する、記憶障害を処置する、認知および/または記憶機能に影響を与える障害の認知症状を処置する方法を提供する。幾つかの実施形態では、方法は、処置を必要とする対象に、治療有効量の、本明細書に記載されるT型カルシウムチャネルアンタゴニストを投与することを含む。処置の対象には、マウス、ラット、他の齧歯類、ウサギ、イヌ、ネコ、ブタ、ウシ、ヒツジ、ウマ、霊長類、およびヒトを挙げることができる。幾つかの実施態様において、対象はヒトである。
本明細書に記載の方法のいずれか、またはその実施形態のいずれかで用いられるT型カルシウムチャネルアンタゴニストは、後述するT型カルシウムチャネルアンタゴニストの1つまたは複数でありうる。
記憶および/または認知を改善する処置のために、1つまたは複数の更なる治療薬が、本明細書に提供される化合物との組合せで使用できる。更なる治療薬の例としては、限定されないが、カルシウムチャネルアンタゴニスト(L型およびT型カルシウムチャネルアンタゴニストを含む)が挙げられる。薬物の組合せは、いずれかの薬物単独より安全または有効でありうる。加えて、本発明の化合物は、本発明の化合物の副作用または毒性の危険性を処置、予防、制御、改善または低減する1つまたは複数の他の薬物と組み合わせて使用することができる。かかる他の薬物は、その薬物に一般的に使用される経路および量により、本発明の化合物と同時に、または経時的に投与することができる。したがって、本発明の医薬組成物には、T型カルシウムチャネル阻害剤に加えて、1つまたは複数の他の活性成分を含有するものが挙げられる。組合せは、単位剤形形態の組合せ製品の一部として、または1つもしくは複数の更なる薬物が処置レジメンの一部として別々の剤形で投与されるキットもしくは処置プロトコルとして投与することができる。
本明細書に記載の方法で用いられるT型カルシウムチャネル阻害剤は、医薬組成物の形態で投与することができる。このように、本発明の開示は、特許請求される処置方法、または本明細書に記載の状態を処置するため医薬の製造に使用される、T型カルシウムチャネル阻害剤と少なくとも1つの薬学的に許容できる担体とを提供する。これらの組成物は、製薬分野で公知の方法で調製することができ、種々の経路により投与することができる。投与は、局所投与(経皮、表皮、眼内、ならびに鼻腔内、膣内および直腸内送達を含む経粘膜を含む)、肺内投与(例えば、ネブライザーなどによる粉末またはエアゾールの吸入または注入、気管内または鼻腔内)、経口または非経口投与であってもよい。非経口投与としては、静脈内、動脈内、皮下、腹腔内、筋肉内または注入もしくは点滴、あるいは頭蓋内(例えばクモ膜下または脳室内)投与が挙げられる。非経口投与は、単回ボーラス投与の形態であってもよく、または連続灌流ポンプによるものであってもよい。局所投与用の医薬組成物および製剤としては、経皮パッチ、軟膏、ローション剤、クリーム、ゲル、ドロップ、坐薬、スプレー、液剤および粉末剤が挙げられうる。従来の医薬用担体、水性、粉末性もしくは油性のベース剤、増粘剤などが必要となり、または望ましい場合もある。
全ての行動実験および電気生理的実験において、雌のUbe3am−/p+ KOマウス(すなわちASマウス)と野生型の雄とを交配させ、F1雑種129S2−C57BL/6のバックグラウンドを有するヘテロ接合ASマウス同腹仔コントロールを作製した。ASマウスは、長期増強(LTP)欠陥が挙げられる認知欠陥を有する。
対照マウス(「wt」)は、ビヒクルで処置し、ASマウスは、ビヒクル、または30mg/kgもしくは60mg/kgの用量のMK−8998(「CX」)を午前と午後の1日2回経口で与えて処置した。投与は、試験の1週間前に実施し、次に行動試験を動物に5週間にわたって実施した。
行動試験の後、動物を殺処分して海馬切片におけるシナプス可塑性を決定するまで、動物に処置を続けた。マウスをLTP測定のために2つの群にわけた。電極は、これらの実験の間で交換した。この設計は、実験変動を低減するが、薬物間の相互比較を可能にしない。
患者は、個体の年齢および教育から予測されるものを超えた認知機能障害の発症および進展を特徴とするが、日常の活動に差し支えるほど重大ではない、軽度認知機能障害を有する。この患者は、New York University(NYU)Paragraph Delayed Recall試験などのアルツハイマー病(AD)Cooperative Study Clinician’s Global Impression of Change for MCI(ADCS CGIC−MCI)、改変AD Assessment Scale−認知症サブスケール(ADAS−cog)、および/またはPatient Global Assessment(PGA)など、1つまたは複数の試験を使用して評価する。
本発明を、「発明の詳細な説明」に関連して記載したが、上記の記載は、あくまで例示を意図するものであり、本発明の範囲を限定することを目的とするものではなく、本発明の範囲は、添付の特許請求の範囲によって定義されると理解すべきである。本発明の多くの実施形態を記載した。しかしながら、本発明の技術思想および範囲から逸脱することなく、様々な修飾をなしうることが理解されよう。したがって、他の側面、効果、実施形態および修飾も、以下の特許請求の範囲内に含まれる。明確さのために、別々の実施形態の文脈で記載されている本発明の特定の特徴を単一の実施形態に組み合わせて提供できることも、更に理解される。逆に、簡素さのために、単一の実施形態の文脈で記載されている本発明の様々な特徴を別々に、または任意の適切な副組合せによって提供することもできる。
Claims (22)
- 対象において記憶および/または認知を改善するために処置する方法であって、前記対象に治療有効量のT型カルシウムチャネルアンタゴニストを投与することを含む方法。
- 前記処置が前記対象において認知を改善する、請求項1に記載の方法。
- 前記処置が前記対象において記憶を改善する、請求項1または2に記載の方法。
- 前記処置が認知障害を対象とする、請求項1から3のいずれか一項に記載の方法。
- 前記処置が記憶障害を対象とする、請求項1から4のいずれか一項に記載の方法。
- 前記処置が、加齢性認知機能障害、失認症、健忘症、健忘障害、筋萎縮性側索硬化症、アンジェルマン症候群、アスペルガー症候群、注意欠陥障害、注意欠陥/活動過多障害(ADHD)、自閉症、脳アミロイド血管症、認知機能不全、アルコールまたは薬物が原因の認知機能障害、せん妄、認知症、AIDS関連認知症、アルコール性認知症、アルツハイマー病、大脳外傷に関連する認知症、クロイツフェルトヤコブ病および他のプリオン誘発性認知症、変性認知症、ハンチントン病、頭蓋内腫瘍に関連する認知症、レビー小体病、多発脳梗塞性認知症、パーキンソン病、パーキンソン病様ALS認知症複合、ピック病、物質誘発性持続性認知症、血管性認知症、ドラベ症候群、頭部外傷、虚血、学習障害、学習機能障害、記憶機能障害、記憶喪失、精神遅滞、軽度認知機能障害、外傷性ストレス障害、プラダー・ウィリー症候群、進行性核上性麻痺、卒中、外傷性脳傷害、トリソミー(21番染色体トリソミー(ダウン症候群)を含む)、およびウェルニッケ・コルサコフ症候群からなる群から選択される状態を対象とする、請求項1から5のいずれか一項に記載の方法。
- 前記処置が、認知および/または記憶機能に影響を与える障害を対象とする、請求項1から5のいずれか一項に記載の方法。
- 前記認知および/または記憶機能に影響を与える障害が、不安障害、気分障害および精神病性障害から選択される、請求項7に記載の方法。
- 前記T型カルシウムチャネルアンタゴニストが、T型カルシウムチャネルを選択的に標的とするカルシウムチャネルアンタゴニストである、請求項1から8のいずれか一項に記載の方法。
- 前記T型カルシウムチャネルアンタゴニストが、L型カルシウムチャネルよりもT型カルシウムチャネルを選択的に標的とするカルシウムチャネルアンタゴニストである、請求項1から9のいずれか一項に記載の方法。
- 前記T型カルシウムチャネルアンタゴニストが小分子である、請求項1から10のいずれか一項に記載の方法。
- 前記T型カルシウムチャネルアンタゴニストが抗体である、請求項1から11のいずれか一項に記載の方法。
- 前記T型カルシウムチャネルアンタゴニストがsiRNAである、請求項1から11のいずれか一項に記載の方法。
- 前記T型カルシウムチャネルアンタゴニストがCaV3.1を選択的に標的とする、請求項1から13のいずれか一項に記載の方法。
- 前記T型カルシウムチャネルアンタゴニストがCaV3.2を選択的に標的とする、請求項1から14のいずれか一項に記載の方法。
- 前記T型カルシウムチャネルアンタゴニストがCaV3.3を選択的に標的とする、請求項1から14のいずれか一項に記載の方法。
- 細胞の膜電位が約−60mVから約−30mVの範囲、例えば約−40mVであるとき、前記T型カルシウムチャネルアンタゴニストが、前記細胞でT型カルシウムチャネルをアンタゴナイズする、請求項1から16のいずれか一項に記載の方法。
- 前記T型カルシウムチャネルアンタゴニストが、ミベフラジル、MK−8998、ジルチアゼム、ニフェジピン、ニトレンジピン、ニモジピン、ニルジピン、ニグルジピン、ニカルジピン、ニソルジピン、アムロジピン、フェロジピン、イスラジピン、リオシジン、ガロパミル、ベラパミル、チアパミル、ピモジド、チオリダジン、NNC55−0396、TTL−1177、アナンダミド、ピモジド、ペンフルリドール、クロピモジド、フルスピリレン、ハロペリドール、ドロペリドール、ベンペリドール、トリペリドール、メルペロン、レンペロン、アザペロン、ドンペリドン、アントラフェニン、アリピペラゾール、シプロフロキサシン、ダピプラゾール、ドロプロピジン、エトペリドン、イトラコナゾール、ケトコナゾール、レボドロプロピジン、メピプラゾール、ナフトピジル、ネファゾドン、ニアプラジン、オキシペルチン、ポサコナゾール、トラゾドン、ウラピジル、ベスナリノン、マニジピン、ニルバジピン、ベニジピン、エホニジピン、フルナリジン、アナンダミド、ロメリジン、ゾニサミド、U−92032、テトラロール、ミベフラジル、NNC55−0396、TTA−A2、TTA−A8、TTA−P1、4−アミノメチル−4−フルオロピペリジン(TTA−P2)、TTA−Q3、TTA−Q6、MK−5395、MK−6526、MK−8998、Z941、Z944、フェンスクシミド、メスクシミド、デスメチルメトスクシミド、エホニジピン、トリメタジオン、ジメタジオン、ABT−639、TTL−1177、KYSO5044、ニッケルおよびクルトキシン、ならびにそれらの組合せからなる群から選択される、請求項1から17のいずれか一項に記載の方法。
- 前記T型カルシウムチャネルアンタゴニストがTTA−A2である、請求項1から18のいずれか一項に記載の方法。
- 前記T型カルシウムチャネルアンタゴニストが実質的に血液脳関門を通過する、請求項1から19のいずれか一項に記載の方法。
- 前記対象に更なる治療薬を投与することを更に含む、請求項1から20のいずれか一項に記載の方法。
- 前記更なる治療薬が更なるT型カルシウムチャネル阻害剤である、請求項21に記載の方法。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022260016A1 (ja) * | 2021-06-07 | 2022-12-15 | 学校法人近畿大学 | T型カルシウムチャネル阻害剤 |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX2018004947A (es) | 2015-10-22 | 2018-11-09 | Cavion Inc | Metodos para el tratamiento de sindrome de angelman y de los trastornos relacionados. |
US11602512B1 (en) | 2016-07-22 | 2023-03-14 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11986451B1 (en) | 2016-07-22 | 2024-05-21 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
UY37341A (es) | 2016-07-22 | 2017-11-30 | Flamel Ireland Ltd | Formulaciones de gamma-hidroxibutirato de liberación modificada con farmacocinética mejorada |
US11602513B1 (en) | 2016-07-22 | 2023-03-14 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11504347B1 (en) | 2016-07-22 | 2022-11-22 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11130750B2 (en) | 2017-02-15 | 2021-09-28 | Cavion, Inc. | Calcium channel inhibitors |
CN110770221B (zh) | 2017-04-26 | 2023-09-08 | 卡维昂公司 | 用于改善记忆和认知以及用于治疗记忆和认知障碍的方法 |
CA3115235A1 (en) | 2018-10-03 | 2020-04-09 | Cavion, Inc. | Treating essential tremor using (r)-2-(4-isopropylphenyl)-n-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)acetamide |
AU2020231916A1 (en) | 2019-03-01 | 2021-08-05 | Flamel Ireland Limited | Gamma-hydroxybutyrate compositions having improved pharmacokinetics in the fed state |
CN114129733A (zh) * | 2021-12-08 | 2022-03-04 | 中国科学院深圳先进技术研究院 | 一种缓解焦虑及相关能量代谢紊乱的药物及其应用 |
CN116392490A (zh) * | 2021-12-27 | 2023-07-07 | 中国科学院广州生物医药与健康研究院 | 氟桂利嗪的用途以及控制细胞内线粒体数量的方法 |
US11779557B1 (en) | 2022-02-07 | 2023-10-10 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11583510B1 (en) | 2022-02-07 | 2023-02-21 | Flamel Ireland Limited | Methods of administering gamma hydroxybutyrate formulations after a high-fat meal |
CN114601928B (zh) * | 2022-04-02 | 2023-03-17 | 首都医科大学 | 一种钙超载介导神经元死亡的标志物及应用 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008533020A (ja) * | 2005-03-09 | 2008-08-21 | メルク エンド カムパニー インコーポレーテッド | キナゾリノンt型カルシウムチャネル拮抗薬 |
KR20090044924A (ko) * | 2007-11-01 | 2009-05-07 | 한국과학기술연구원 | 피라졸릴카르복스아미도알킬피페라진 유도체 및 이의제조방법 |
JP2009534320A (ja) * | 2006-04-12 | 2009-09-24 | メルク エンド カムパニー インコーポレーテッド | ピリジルアミドt型カルシウムチャンネルアンタゴニスト |
US20100137403A1 (en) * | 2008-07-10 | 2010-06-03 | Scott Malstrom | Method for enhancing cognition or inhibiting cognitive decline |
JP2011518860A (ja) * | 2008-04-29 | 2011-06-30 | ファーネクスト | ゾニサミドおよびアカンプロセートを用いるアルツハイマー病および関連障害の処置のための併用組成物 |
Family Cites Families (68)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1319144C (en) | 1986-11-14 | 1993-06-15 | Quirico Branca | Tetrahydronaphthalene derivatives |
AU2436792A (en) | 1991-08-16 | 1993-03-16 | Merck & Co., Inc. | Quinazoline derivatives as inhibitors of hiv reverse transcriptase |
DE69729179T2 (de) | 1996-02-14 | 2004-12-30 | Isis Pharmaceuticals, Inc., Carlsbad | Lückenhaft Zucker-modifizierte Oligonukleotide |
AU2001235363A1 (en) | 2000-02-25 | 2001-09-03 | Novo-Nordisk A/S | Mibefradil analogues and their use |
US7112319B2 (en) | 2001-04-06 | 2006-09-26 | The Research Foundation Of The City University Of New York | Identification, diagnosis, and treatment of neuropathologies, neurotoxicities, tumors, and brain and spinal cord injuries using microelectrodes with microvoltammetry |
ATE402999T1 (de) | 2002-01-17 | 2008-08-15 | Univ British Columbia | Bispezifische antisense oligonukleotide die igfbp-2 und igfbp-5 inhibieren und deren verwendung |
EP1553946A4 (en) | 2002-10-17 | 2008-07-16 | Merck & Co Inc | SLEEP IMPROVEMENT USING T-TYPE CALCIUM CHANNEL ANTAGONISTS |
US8487002B2 (en) | 2002-10-25 | 2013-07-16 | Paladin Labs Inc. | Controlled-release compositions |
WO2004084879A1 (en) | 2003-03-21 | 2004-10-07 | Dynogen Pharmaceuticals, Inc. | Methods for treating lower urinary tract disorders using smooth muscle modulators and alpha-2-delta subunit calcium channel modulators |
US7166603B2 (en) | 2003-07-23 | 2007-01-23 | Bristol-Myers Squibb Co. | Dihydropyrimidone inhibitors of calcium channel function |
US7157461B2 (en) | 2003-07-23 | 2007-01-02 | Bristol-Myers Squibb Co. | Substituted dihydropyrimidine inhibitors of calcium channel function |
KR100610731B1 (ko) | 2004-02-24 | 2006-08-09 | 한국과학기술연구원 | T-형 칼슘 채널 차단제로서 유용한 3,4-디히드로퀴나졸린유도체 및 그의 제조 방법 |
US7504431B2 (en) | 2004-04-16 | 2009-03-17 | Bristol-Myers Squibb Company | Sulfonyl amide inhibitors of calcium channel function |
CA2576191C (en) | 2004-08-20 | 2013-03-19 | University Of Virginia Patent Foundation | T type calcium channel inhibitors |
CA2576186A1 (en) | 2004-08-20 | 2006-03-02 | University Of Virginia Patent Foundation | T type calcium channel blockers and the treatment of diseases |
CA2611153A1 (en) | 2005-06-23 | 2007-01-04 | Merck & Co., Inc. | 3-fluoro-piperidine t-type calcium channel antagonists |
CA2611639A1 (en) | 2005-06-29 | 2007-01-04 | Merck & Co., Inc. | 4-fluoro-piperidine t-type calcium channel antagonists |
EP1906215A4 (en) | 2005-07-14 | 2012-04-18 | Teijin Chemicals Ltd | FOAM SHEET AND LIQUID CRYSTAL DISPLAY |
KR100654328B1 (ko) | 2005-08-26 | 2006-12-08 | 한국과학기술연구원 | 피페라지닐알킬피라졸계 t-타입 칼슘 채널 억제 화합물 및이의 제조방법 |
WO2007073497A2 (en) | 2005-12-22 | 2007-06-28 | Icagen, Inc. | Calcium channel antagonists |
KR100743255B1 (ko) | 2006-05-04 | 2007-07-27 | 한국과학기술연구원 | T-형 칼슘 채널에 활성을 지닌 신규1,3-다이옥소아이소인돌 유도체 |
KR100749843B1 (ko) | 2006-07-13 | 2007-08-21 | 한국과학기술연구원 | T-타입 칼슘 채널에 억제 활성을 지닌 신규2,4-디옥소-퀴나졸린 유도체 및 이의 제조방법 |
KR100969686B1 (ko) | 2006-08-07 | 2010-07-14 | 한국과학기술연구원 | 신규한 티아졸계 화합물 및 이를 함유하는 t-형 칼슘 채널저해제 |
EP2061462A2 (en) | 2006-09-15 | 2009-05-27 | Schering Corporation | Treating pain, diabetes and lipid metabolism disorders |
US20080076750A1 (en) | 2006-09-15 | 2008-03-27 | Aslanian Robert G | Azetidinone Derivatives and Methods of Use Thereof |
WO2008033447A1 (en) | 2006-09-15 | 2008-03-20 | Schering Corporation | Azetidine and azetidone derivatives useful in treating pain and disorders of lipid metabolism |
AR062790A1 (es) | 2006-09-15 | 2008-12-03 | Schering Corp | Derivados de azetidina utiles en el tratamiento del dolor, diabetes y trastornos del metabolismo de los lipidos |
CN101583612A (zh) | 2006-09-15 | 2009-11-18 | 先灵公司 | 治疗脂质代谢障碍的氮杂环丁酮衍生物 |
WO2008050200A1 (en) | 2006-10-24 | 2008-05-02 | Pfizer Products Inc. | Oxadiazole compounds as calcium channel antagonists |
US20080227823A1 (en) | 2007-03-12 | 2008-09-18 | Hassan Pajouhesh | Amide derivatives as calcium channel blockers |
WO2008112715A2 (en) * | 2007-03-12 | 2008-09-18 | Vm Discovery Inc. | Novel agents of calcium ion channel modulators |
WO2008117148A1 (en) | 2007-03-23 | 2008-10-02 | Pfizer Products Inc. | Substituted oxadiazole analogs as calcium channel antagonists |
CA2685753A1 (en) | 2007-05-09 | 2008-11-20 | Neuromed Pharmaceuticals Ltd. | Bicyclic pyrimidine derivatives as calcium channel blockers |
KR100863239B1 (ko) | 2007-05-23 | 2008-10-15 | 한국과학기술연구원 | 신규한 2-이미노-1,3-티아졸린계 화합물 및 이를 함유하는t-형 칼슘 채널 저해제 |
CA2692783A1 (en) | 2007-07-10 | 2009-01-15 | Merck Sharp & Dohme Corp. | Quinazolinone t-type calcium channel antagonists |
KR101079459B1 (ko) | 2007-09-14 | 2011-11-03 | 이화여자대학교 산학협력단 | 신규한 화합물, 이의 제조방법 및 이를 포함하는 통증억제용 조성물 |
JP2011500808A (ja) | 2007-10-24 | 2011-01-06 | メルク・シャープ・エンド・ドーム・コーポレイション | 複素環アミドt型カルシウムチャネルアンタゴニスト |
AU2008317351A1 (en) | 2007-10-24 | 2009-04-30 | Merck Sharp & Dohme Corp. | Pyrazinyl amide T-type calcium channel antagonists |
AU2008317353B2 (en) | 2007-10-24 | 2014-08-07 | Merck Sharp & Dohme Llc | Heterocycle phenyl amide T-type calcium channel antagonists |
WO2009056934A1 (en) | 2007-10-31 | 2009-05-07 | Pfizer Products Inc. | 1,4-dihydronaphthyridine derivatives |
CA2722706A1 (en) | 2008-04-28 | 2009-11-05 | Zalicus Pharmaceuticals Ltd. | Di-t-butylphenyl piperazines as calcium channel blockers |
US20090298834A1 (en) | 2008-06-02 | 2009-12-03 | Hassan Pajouhesh | 4-(aminomethyl)cyclohexanamine derivatives as calcium channel blockers |
US8377968B2 (en) | 2008-06-02 | 2013-02-19 | Zalicus Pharmaceuticals, Ltd. | N-piperidinyl acetamide derivatives as calcium channel blockers |
KR101014887B1 (ko) | 2008-06-26 | 2011-02-15 | 한국과학기술연구원 | 칼슘이온 채널 조절제로서 유효한 이미다졸릴알킬카르보닐유도체 및 그의 제조방법 |
KR20100005476A (ko) | 2008-07-07 | 2010-01-15 | 한국과학기술연구원 | T-형 칼슘 채널에 활성을 지닌 신규 아이소인돌리논유도체 및 이의 제조방법 |
GB0813142D0 (en) * | 2008-07-17 | 2008-08-27 | Glaxo Group Ltd | Novel compounds |
KR101052620B1 (ko) | 2008-08-28 | 2011-07-29 | 한국과학기술연구원 | 신규 페닐아세테이트 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 t-형 칼슘 이온 채널의 활성에 의해 유발되는 질환의 예방 또는 치료용 조성물 |
KR101052065B1 (ko) | 2008-10-15 | 2011-07-27 | 한국과학기술연구원 | 칼슘이온 채널 조절제로서 유효한 피라졸릴메틸아민-피페라진 유도체와 이의 제조방법 |
TW201028421A (en) | 2009-01-15 | 2010-08-01 | Abbott Lab | Novel benzenesulfonamides as calcium channel blockers |
CN102458416A (zh) | 2009-06-05 | 2012-05-16 | 陶制药有限责任公司 | 用于治疗癌症或癌前病症的交错方法 |
BR112012003179A2 (pt) | 2009-08-12 | 2016-03-01 | Carlos Alberto Barcelo Rojas | sistema bio-eletrônico |
JP5846372B2 (ja) | 2010-01-29 | 2016-01-20 | 国立大学法人 岡山大学 | Dravet症候群の発症可能性の判定方法およびその利用 |
US8575361B2 (en) | 2010-03-02 | 2013-11-05 | Concert Pharmaceuticals Inc. | Tetrahydronaphthalene derivatives |
WO2012032415A2 (en) | 2010-09-08 | 2012-03-15 | Pronova Biopharma Norge As | Compositions comprising a fatty acid oil mixture comprising epa and dha in free acid form, a surfactant, and a statin |
WO2012094612A1 (en) * | 2011-01-07 | 2012-07-12 | Zenyaku Kogyo Kabushikikaisha | Method of treating essential tremor |
AU2013259617A1 (en) | 2012-05-08 | 2014-11-27 | Zafgen, Inc. | Treating hypothalamic obesity with MetAP2 inhibitors |
SG11201505206WA (en) | 2013-01-10 | 2015-07-30 | Tau Therapeutics Llc | T-type calcium channel inhibitors for treatment of cancer |
US10292989B2 (en) | 2014-03-28 | 2019-05-21 | University Of Virginia Patent Foundation | General anesthetics that are not neurotoxic |
KR101679262B1 (ko) | 2015-06-08 | 2016-11-24 | 한국과학기술연구원 | 4-이소프로필크로만-3-올 화합물 |
GB2539472A (en) | 2015-06-17 | 2016-12-21 | Gw Res Ltd | Use of cannabinoids in the treatment of epilepsy |
US9351968B1 (en) | 2015-09-09 | 2016-05-31 | Ovid Therapeutics Inc | Methods of treating developmental disorders using pipradrol |
MX2018004947A (es) | 2015-10-22 | 2018-11-09 | Cavion Inc | Metodos para el tratamiento de sindrome de angelman y de los trastornos relacionados. |
CN105534977A (zh) * | 2016-01-14 | 2016-05-04 | 山东大学 | T型钙离子通道抑制剂nnc55-0396在制备抗神经退行性疾病药物中的应用 |
CN110770221B (zh) | 2017-04-26 | 2023-09-08 | 卡维昂公司 | 用于改善记忆和认知以及用于治疗记忆和认知障碍的方法 |
CN110799215A (zh) | 2017-04-26 | 2020-02-14 | 卡维昂公司 | 治疗Dravet综合征的方法 |
GB2571978A (en) * | 2018-03-15 | 2019-09-18 | Andre Fisahn | Uses, compositions and methods |
CA3115235A1 (en) | 2018-10-03 | 2020-04-09 | Cavion, Inc. | Treating essential tremor using (r)-2-(4-isopropylphenyl)-n-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)acetamide |
TW202122084A (zh) | 2019-10-02 | 2021-06-16 | 美商卡凡恩公司 | 用於治療神經毒性之方法及材料 |
-
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008533020A (ja) * | 2005-03-09 | 2008-08-21 | メルク エンド カムパニー インコーポレーテッド | キナゾリノンt型カルシウムチャネル拮抗薬 |
JP2009534320A (ja) * | 2006-04-12 | 2009-09-24 | メルク エンド カムパニー インコーポレーテッド | ピリジルアミドt型カルシウムチャンネルアンタゴニスト |
KR20090044924A (ko) * | 2007-11-01 | 2009-05-07 | 한국과학기술연구원 | 피라졸릴카르복스아미도알킬피페라진 유도체 및 이의제조방법 |
JP2011518860A (ja) * | 2008-04-29 | 2011-06-30 | ファーネクスト | ゾニサミドおよびアカンプロセートを用いるアルツハイマー病および関連障害の処置のための併用組成物 |
US20100137403A1 (en) * | 2008-07-10 | 2010-06-03 | Scott Malstrom | Method for enhancing cognition or inhibiting cognitive decline |
Non-Patent Citations (2)
Title |
---|
LEARN. MEM. (1999) VOL.6, NO.5, P.399-416, JPN6022055621, ISSN: 0004958944 * |
NEUROBIOL. DIS. (2016) VOL.94, P.106-115, JPN6022014355, ISSN: 0004958943 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022260016A1 (ja) * | 2021-06-07 | 2022-12-15 | 学校法人近畿大学 | T型カルシウムチャネル阻害剤 |
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RU2019137952A (ru) | 2021-05-26 |
SG11201909960UA (en) | 2019-11-28 |
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CA3061720A1 (en) | 2018-11-01 |
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SG10202111885PA (en) | 2021-12-30 |
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WO2018200850A1 (en) | 2018-11-01 |
IL270180B (en) | 2022-06-01 |
EP3615521A4 (en) | 2021-02-17 |
AU2018260699B2 (en) | 2022-04-28 |
EP3615521A1 (en) | 2020-03-04 |
RU2019137952A3 (ja) | 2021-05-31 |
CN110770221A (zh) | 2020-02-07 |
AU2018260699A1 (en) | 2019-11-14 |
KR102654466B1 (ko) | 2024-04-08 |
KR20200003394A (ko) | 2020-01-09 |
CN110770221B (zh) | 2023-09-08 |
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