JP5898815B2 - 新規なピラゾロピリミジン - Google Patents
新規なピラゾロピリミジン Download PDFInfo
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- JP5898815B2 JP5898815B2 JP2015502311A JP2015502311A JP5898815B2 JP 5898815 B2 JP5898815 B2 JP 5898815B2 JP 2015502311 A JP2015502311 A JP 2015502311A JP 2015502311 A JP2015502311 A JP 2015502311A JP 5898815 B2 JP5898815 B2 JP 5898815B2
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Classifications
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C07—ORGANIC CHEMISTRY
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
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- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Diabetes (AREA)
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- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Hematology (AREA)
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- Cardiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- Surgery (AREA)
- Gynecology & Obstetrics (AREA)
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Description
WO2004/089471は、11β−ヒドロキシステロイドデヒドロゲナーゼ1型(11βHSD1)の活性のアンタゴニストとして働くと主張されるピラゾロピリミジンを開示している。
特に指示しない限り、本明細書および添付される特許請求の範囲の全体を通して、所与の化学式または名称は、互変異性体と、全ての立体、光学および幾何異性体(例えば、鏡像異性体、ジアステレオマー、E/Z異性体など)と、これらのラセミ化合物およびそれぞれの鏡像対が異なる割合にある混合物、ジアステレオマーの混合物、または前述の形態のいずれかの混合物であってそのような異性体および鏡像異性体が存在するもの、ならびに医薬品として許容されるこれらの塩およびこれらの溶媒和物を含めた塩であって、例えば遊離化合物の溶媒和物もしくは化合物の塩の溶媒和物を含めた水和物などを包含するものとする。
「医薬品として許容される」という文言は、堅実な医学的判断の範囲内で、過剰な毒性、刺激、アレルギー応答またはその他の問題もしくは合併症なしに人間および動物の組織と接触させて使用するのに適し、かつ妥当な利益/リスク比と釣り合った状態の化合物、材料、組成物および/または剤形を指すのに本明細書では用いられる。
本明細書で使用される「医薬品として許容される塩」は、開示された化合物の誘導体を指し、これは親化合物が酸またはその塩基塩を作製することによって変性したものである。医薬品として許容される塩の例には、アミンなどの塩基性残基の鉱酸塩または有機酸塩;カルボン酸などの酸性残基のアルカリ塩または有機塩;および同様のものが含まれるが、これらに限定するものではない。例えば、そのような塩には、アンモニア、L−アルギニン、ベタイン、ベネタミン、ベンザチン、水酸化カルシウム、コリン、デアノール、ジエタノールアミン(2,2’−イミノビス(エタノール))、ジエチルアミン、2−(ジエチルアミノ)−エタノール、2−アミノエタノール、エチレンジアミン、N−エチル−グルカミン、ヒドラバミン、1H−イミダゾール、リシン、水酸化マグネシウム、4−(2−ヒドロキシエチル)−モルホリン、ピペラジン、水酸化カリウム、1−(2−ヒドロキシエチル)−ピロリジン、水酸化ナトリウム、トリエタノールアミン(2,2’,2”−ニトリロトリス(エタノール))、トロメタミン、水酸化亜鉛、酢酸、2.2−ジクロロ−酢酸、アジピン酸、アルギン酸、アスコルビン酸、L−アスパラギン酸、ベンゼンスルホン酸、安息香酸、2,5−ジヒドロキシ安息香酸、4−アセトアミド−安息香酸、(+)−ショウノウ酸、(+)−ショウノウ−10−スルホン酸、炭酸、ケイ皮酸、クエン酸、シクラミン酸、デカン酸、ドデシル硫酸、エタン−1,2−ジスルホン酸、エタンスルホン酸、2−ヒドロキシ−エタンスルホン酸、エチレンジアミン四酢酸、ギ酸、フマル酸、ガラクタル酸、ゲンチジン酸、D−グルコヘプトン酸、D−グルコン酸、D−グルクロン酸、グルタミン酸、グルタル酸、2−オキソ−グルタル酸、グリセロリン酸、グリシン、グリコール酸、ヘキサン酸、馬尿酸、臭化水素酸、塩酸、イソ酪酸、DL−乳酸、ラクトビオン酸、ラウリン酸、リシン、マレイン酸、(−)−L−リンゴ酸、マロン酸、DL−マンデル酸、メタンスルホン酸、ガラクタル酸、ナフタレン−1,5−ジスルホン酸、ナフタレン−2−スルホン酸、1−ヒドロキシ−2−ナフトエ酸、ニコチン酸、硝酸、オクタン酸、オレイン酸、オロト酸、シュウ酸、パルミチン酸、パモ酸(エンボン酸)、リン酸、プロピオン酸、(−)−L−ピログルタミン酸、サリチル酸、4−アミノ−サリチル酸、セバシン酸、ステアリン酸、コハク酸、硫酸、タンニン酸、(+)−L−酒石酸、チオシアン酸、p−トルエンスルホン酸、およびウンデシレン酸からの塩が含まれる。さらなる医薬品として許容される塩は、アルミニウム、カルシウム、リチウム、マグネシウム、カリウム、ナトリウム、および亜鉛などのような金属の陽イオンにより形成することができる(Pharmaceutical salts, Berge, S.M.et al., J.Pharm.Sci., (1977), 66, 1-19も参照)。
本発明の医薬品として許容される塩は、従来の化学的方法によって、塩基性または酸性部分を含有する親化合物から合成することができる。一般にそのような塩は、これらの化合物の遊離酸または塩基形態と十分な量の適切な塩基または酸とを、水中で、またはエーテル、酢酸エチル、エタノール、イソプロパノールもしくはアセトリトリルのような有機希釈剤中で、またはこれらの混合物中で反応させることによって調製することができる。例えば本発明の化合物を精製しまたは単離するのに有用である、上述のもの以外の酸の塩(例えば、トリフルオロ酢酸塩)も、本発明の一部を構成する。
化合物の生物学的活性を、下記の方法により決定した:
細胞系で発現したmGluR5受容体の活性化は、細胞内カルシウム濃度の増加をもたらす。カルシウム感受性蛍光色素および適切な蛍光プレートリーダーを使用すると、この機能的応答は検出可能になり定量可能になる。この技法は、mGluR5受容体の薬理学的修飾を特徴付けるのに使用することができた。
アッセイ実行の72時間前に、培地を、抗生剤を含まずに10%ウシ胎児血清を含むDMEMに置き換えることによって、mGluR5a発現が誘導された。アッセイ実行の24時間前に、細胞培地を、グルタミンおよびフェノールレッドなしで、DMEM、10%ウシ胎児血清による2つの洗浄ステップの後に交換した。アッセイ当日、ベルセンにより細胞を培養フラスコから取り出し、洗浄し、5mMグルコースおよび10mM HEPES pH7.4を含む変性Ringer液中に再懸濁し、ポリ−D−リシンでコーティングされた384ウェルプレート上に、ウェル当たり10,000細胞/60μlの密度で蒔いた。インキュベーター内で1時間の播種時間が過ぎた後、製造業者の手引きに従いカルシウム4キット(Molecular Devices Inc.、R8141)から4倍濃度の色素溶液20μlを添加することによって、細胞を色素染色し、さらに100分間インキュベートした。化合物を、DMSO中での11ポイント連続希釈、およびアッセイ緩衝液(puffer)(変性Ringer)中への最終希釈ステップによって調製して、最終DMSO濃度がアッセイにおいて1%であることを確認した。
測定は、2ステップ手順で行った。最初の測定は、細胞プレートに化合物を添加した直後に行って、定量し、非特異的作用(例えば、自己蛍光)に関連した化合物に関して補正をした。5分後、化合物の拮抗的活性を、EC90濃度のアゴニストグルタメート(EC90濃度は、グルタメート用量応答曲線により制御した。)を添加することによって測定した。全ての測定は、蛍光定量的撮像プレートリーダー(FLIPR、Molecular Devices Inc.)で行った。IC50値およびHill勾配は、蛍光シグナルのピーク高さを使用した、AssayExplorerソフトウェアによる11ポイント4パラメトリック非線形曲線当てはめから誘導した。
11β−HSD1のin vitro阻害を、ヒト肝臓マイクロソームによりコルチステロンから発生したコルチゾールを検出するHTRF(均質時間分解蛍光)技術(cisbio international、フランス)により決定した。化合物を、1時間、37℃で、NADPH(200μM)およびコルチゾン(80nM)を含有するTris緩衝液(20mM tris、5mM EDTA、pH6.0)中でインキュベートした。次いで反応で発生したコルチゾールを、2種のHTRFコンジュゲート:XL665に結合したコルチゾールおよびユーロピウムクリプテートで標識された抗コルチゾール抗体を用いる、競合的免疫アッセイにより検出した。検出反応のためのインキュベーション時間は2時間であった。コルチゾールの量は、ウェルの時間分解蛍光を読み取ることによって決定した(Ex 320/75nm;Em 615/8.5nmおよび665/7.5nm)。次いで2つの放出シグナルの比を計算した(Em665*10000/Em615)。各アッセイは、非阻害コルチゾール発生のための対照として化合物の代わりにビヒクル対照を用いたインキュベーション(100%CTL;「高値」)と、完全阻害酵素およびコルチゾールバックグランドのための対照としてカルベノキソロンを用いたインキュベーション(0%CTL;「低値」)とを含んでいた。各アッセイは、蛍光データをコルチゾール濃度に転換するためのコルチゾールの較正曲線も含んでいた。
各化合物の阻害パーセント(%CTL)を、カルベノキソロンシグナルに対して決定し、IC50曲線を作成した。
本発明は、精神医学的疾患、障害または状態;神経疾患、障害または状態の治療;ならびに疼痛疾患、障害または状態の治療および/または予防を含むがこれらに限定することのない、代謝型グルタミン酸5受容体の活性の阻害が療法上の利益である疾患、障害および/または状態の治療および/または予防に有用な、化合物を対象とする。
好ましくは本発明による化合物は、てんかん、アルツハイマー病、認知障害、記憶欠損、パーキンソン病、エイズ関連認知症、無酸素性虚血性損傷(卒中)、注意欠陥/多動性障害、振戦せん妄、神経変性、神経毒性、脆弱X、筋委縮性側索硬化症、ハンチントン舞踏病、自閉症、精神遅滞、ダウン症候群および頭部外傷からなる群から選択された、神経疾患、障害または状態の治療に有用である。好ましくは本発明による化合物は、慢性および急性片頭痛;神経痛、ヘルペス後神経痛、三叉神経痛;化学療法誘発性ニューロパシー;炎症および神経因性疼痛、糖尿病性ニューロパシー、関節炎、リウマチ様疾患、腰痛、術後疼痛、アンギナ、腎または胆道疝痛、月経、痛風などのその他の状態に関連した疼痛からなる群から選択された、疼痛疾患、障害または状態の治療、予防または寛解に有用である。
さらに本発明は、代謝型グルタミン酸5受容体の活性が療法上有益なものである、疾患、障害または状態の治療および/または予防のための化合物の使用に関する。
好ましくは本発明は、精神障害、統合失調症、抑うつおよびその他の気分障害(双極性)、不安障害(GAD、パニック、心的外傷後ストレス、恐怖症、急性ストレス、パラノイア)、強迫性障害、食欲不振/過食症、人格障害、成長障害、または性機能不全、物質関連障害、衝動制御障害からなる群から選択された、精神医学的疾患、障害、または状態の治療に有用であり、後の2つの群の障害には、物質(例えば、アルコール、ニコチン、その他の薬物物質)または活動(例えば、病的賭博、過食、性的活動)に対する身体的なまたは感情的な依存または中毒が含まれる。
好ましくは本発明は、てんかん、アルツハイマー病、認知障害、記憶欠損、パーキンソン病、エイズ関連認知症、無酸素性虚血性損傷(卒中)、注意欠陥/多動性障害、振戦せん妄、神経変性、神経毒性、脆弱X、筋委縮性側索硬化症、ハンチントン舞踏病、自閉症、精神遅滞、ダウン症候群および頭部外傷からなる群から選択された、神経疾患、障害または状態の治療のための、化合物の使用に関する。
好ましくは本発明は、慢性および急性片頭痛;神経痛(ヘルペス後神経痛、三叉神経痛);化学療法誘発性ニューロパシー;炎症および神経因性疼痛であって、糖尿病性ニューロパシー、関節炎、リウマチ様疾患、腰痛、術後疼痛を含めた疼痛、その他の状態(アンギナ、腎または胆道疝痛、月経、痛風)に関連した疼痛からなる群から選択された疼痛疾患、障害または状態の治療、予防または寛解のための、化合物の使用に関する。本発明の別の態様において、本発明は、本発明の化合物の有効量を人間に投与することを含む、上述の疾患および状態を治療および/または予防するための方法に関する。
1日当たり適用可能な本発明の化合物の用量範囲は、通常は1〜1000mg、好ましくは5〜800mg、より好ましくは5〜500mgである。各投薬単位は、1〜1000mg、好ましくは1〜500mgを都合良く含有していてもよい。
実際の、医薬品として有効な量または療法上の投薬は、当然ながら、患者の年齢および体重、投与経路、および疾患の重症度などの当業者に公知の因子に依存することになる。いずれにせよ、患者固有の状態に基づいて医薬品として有効な量を送達させる投薬量および手法で、組合せが投与される。
本発明の化合物を投与するのに適切な調製物は、当業者に明らかであり、例えば、錠剤、丸薬、カプセル、坐薬、ロゼンジ、トローチ、溶液、シロップ、エリキシル、サッシェ、注射剤、吸入剤、粉末などを含むことになる。医薬品として活性な(1種または複数の)化合物の含量は、全体として組成物の0.1〜95重量%、好ましくは5.0〜90重量%の範囲にあるべきである。
適切な錠剤は、例えば、本発明の1種または複数の化合物を、公知の賦形剤、例えば不活性希釈剤、担体、崩壊剤、助剤、界面活性剤、結合剤および/または潤滑剤と混合することによって得ることができる。錠剤は、数層からなるものであってもよい。
本発明による化合物は、特に上述の疾患および状態の治療、予防または寛解のために、その他の活性物質と併せて使用されてもよい。そのような組合せに適切なその他の活性物質には、例えば、述べた適応の1つに関して本発明による代謝型グルタミン酸5受容体アンタゴニストの療法上の効果を増強するもの、および/または本発明による代謝型グルタミン酸5受容体アンタゴニストの投薬量を低減させるものが含まれる。そのような組合せに適切な療法薬には、例えば、H2遮断薬(例えば、シメチジン、ラニチジン)、プロトンポンプ阻害剤、例えばピリジニルメチルスルフィニルベンズイミダゾール(例えば、オメプラゾール、エソメプラゾール、ランソプラゾール、パントプラゾール、ラベプラゾール、またはレミノプラゾールなどの関連物質)など、抗アルツハイマー薬、例えばβ−セクレターゼ阻害剤、γ−セクレターゼ阻害剤、ムスカリンアゴニスト、ムスカリンポテンシエーター、HMG−CoAレダクターゼ阻害剤、NSAID、および抗アミロイド抗体が含まれる。このリストには、催眠鎮静薬、抗不安薬、抗精神病薬、抗てんかん薬、選択的セロトニン再取込み阻害剤、選択的セロトニンおよびノルエピネフリン(norepihephrine)再取込み阻害剤、三環系抗うつ剤、モノアミンオキシダーゼ阻害剤、5−HT2アゴニストまたはアンタゴニスト、GlyT1阻害剤、ならびに限定するものではないが、リスペリドン、クロザピン、オランザピン、ハロペリドール、フルオキセチン、プラゼパム、サノメリン、リチウム、フェノバルビトールおよびこれらの塩、およびこれらの組合せなども含まれる。
さらに、レボドーパ(選択的脳外デカルボキシラーゼ阻害剤を含みまたは含まない)、ビペリデンなどの抗コリン作動薬、エンタカポンなどのCOMT阻害剤、A2aアデノシンアンタゴニスト、コリン作動性アゴニスト、NMDA受容体アゴニストまたはアンタゴニスト、およびドーパミンアゴニストのような薬物との組合せである。リストはさらに、オピエートアゴニストまたはアンタゴニスト、カルシウムチャネルアンタゴニスト、ナトリウムチャネルアンタゴニスト、COX−2選択的阻害剤、NK1アンタゴニスト、GABA−A受容体モジュレーター、ドーパミンアゴニストまたはアンタゴニスト、ノルエピネフリンモジュレーター、ニコチンアゴニストまたはアンタゴニストであってニコチンを含むもの、およびムスカリンアゴニストまたはアンタゴニストを含む。そのような組合せにも適切な療法薬には、例えば、メタドン、レボ−α−アセチルマトドール(acetylmathdol)、ブプレノルフィン、およびナルトレキソン、ジスルフィラム、およびアカムプロセート、ブスピロン、バルプロエート、およびガバペンチンが含まれる。
以下に記述される化合物は、質量分析計でイオン化した後のその特性質量、薄層クロマトグラフィープレートでのそのRf値、および/または分析HPLCでのその保持時間を通して特徴付けられた。
カラム:
勾配1(G1):
溶媒A:水(0.1%ギ酸を含む。)
溶媒B:アセトニトリル(0.1%ギ酸を含む。)
HPLCシステム:DA−およびMS−検出器を備えたAgilent 1100
勾配(室温):
溶媒A:水(0.1%トリフルオロ酢酸を含む。)
溶媒B:メタノール(0.1%トリフルオロ酢酸を含む。)
HPLCシステム:DA−およびMS−検出器を備えたAgilent 1100
勾配(温度60℃)
中間体1
5−ブロモ−アゼパン−4−オンヒドロブロミド
収量:79.0g(理論値の87%)
ESI−MS: m/z=192(M+H)+
Rt(HPLC): 0.64分(方法B)
2−エチル−5,6,7,8−テトラヒドロ−4H−チアゾロ[4,5−d]アゼピンヒドロブロミド
収量:0.39g(定量的)
ESI−MS: m/z=183(M+H)+
Rt(HPLC): 0.39分(方法J)
2−メトキシ−5,6,7,8−テトラヒドロ−4H−チアゾロ[4,5−d]アゼピントリフルオロアセテート
収量:1.26g(理論値の51%)
ESI−MS: m/z=333(M+H)+
収量:0.40g(理論値の47%)、Rt(HPLC):1.49分(方法J)
収量:90mg(理論値の23%)、ESI−MS: m/z=171(M+H)+;Rt(HPLC):0.15分(方法J)。
2−メチル−5,6,7,8−テトラヒドロ−4H−チアゾロ[4,5−d]アゼピンヒドロクロリド
3−クロロ−6,7,8,9−テトラヒドロ−5H−1,2,7−トリアザ−ベンゾシクロヘプテントリフルオロ−アセテート
2−メトキシメチル−5,6,7,8−テトラヒドロ−4H−チアゾロ[2,3−d]アゼピンヒドロブロミド
5,6,7,8−テトラヒドロ−4H−チアゾロ[4,5−d]アゼピンヒドロクロリド
2−イソプロピル−5,6,7,8−テトラヒドロ−4H−チアゾロ[4,5−d]アゼピン
6,7,8,9−テトラヒドロ−5H−ピリド[2,3−d]アゼピン
(例1)
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(2−クロロ−5,6,8,9−テトラヒドロ−ピリド[2,3−d]アゼピン−7−イル)−メタノン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(2−メトキシ−5,6,8,9−テトラヒドロ−ピリド[2,3−d]アゼピン−7−イル)−メタノン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(4,5,7,8−テトラヒドロ−チエノ[2,3−d]アゼピン−6−イル)−メタノン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(2−エチル−4,5,7,8−テトラヒドロ−チアゾロ[4,5−d]アゼピン−6−イル)−メタノン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(4,5,7,8−テトラヒドロ−チアゾロ[4,5−d]アゼピン−6−イル)−メタノン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(2−メチル−4,5,7,8−テトラヒドロ−3H−1λ*4*−チアゾロ[4,5−d]アゼピン−6−イル)−メタノン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(3−クロロ−5,6,8,9−テトラヒドロ−1,2,7−トリアザ−ベンゾシクロヘプテン−7−イル)−メタノン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(2−メトキシメチル−4,5,7,8−テトラヒドロ−チアゾロ[4,5−d]アゼピン−6−イル)−メタノン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−4,5,7,8−テトラヒドロ−チアゾロ[4,5−d]アゼピン−6−イル)−メタノン
(6−クロロ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(4,5,7,8−テトラヒドロ−チアゾロ[4,5−d]アゼピン−6−イル)−メタノン
6−(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−カルボニル)−3,4,5,6,7,8−ヘキサヒドロ−チアゾロ[4,5−d]アゼピン−2−オン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(2−イソプロピル−4,5,7,8−テトラヒドロ−チアゾロ[4,5−d]アゼピン−6−イル)−メタノン
(6−クロロ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(2−メチル−4,5,7,8−テトラヒドロ−チアゾロ[4,5−d]アゼピン−6−イル)−メタノン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(5,6,8,9−テトラヒドロ−ピリド[2,3−d]アゼピン−7−イル)−メタノン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(1−メチル−4,5,7,8−テトラヒドロ−1H−イミダゾ[4,5−d]アゼピン−6−イル)−メタノン
6−(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−カルボニル)−3−メチル−3,4,5,6,7,8−ヘキサヒドロ−チアゾロ[4,5−d]アゼピン−2−オン
(6−ブロモ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(6−メチル−1,4,5,6−テトラヒドロ−2H−アゼピノ[4,5−b]インドール−3−イル)−メタノン
(6−クロロ−ピラゾロ[1,5−a]ピリミジン−2−イル)−(2−イソプロピル−4,5,7,8−テトラヒドロ−チアゾロ[4,5−d]アゼピン−6−イル)−メタノン
6−(6−クロロ−ピラゾロ[1,5−a]ピリミジン−2−カルボニル)−3,4,5,6,7,8−ヘキサヒドロ−チアゾロ[4,5−d]アゼピン−2−オン
尚、本発明は以下の事項を含んでいる。
〔1〕下記の群から選択される化合物またはその医薬品として許容される塩。
〔2〕医薬として使用される、前記〔1〕に記載の化合物。
〔3〕医薬品として許容される助剤、希釈剤および/または担体と混合された、少なくとも1種の前記〔1〕に記載の化合物またはその医薬品として許容される塩を含む、医薬品組成物。
〔4〕精神医学的疾患、障害もしくは状態;神経疾患、障害もしくは状態;または疼痛疾患、障害もしくは状態の治療に使用される、前記〔1〕に記載の化合物またはその医薬品として許容される塩。
〔5〕治療がなされる精神医学的疾患、障害または状態が、精神障害、統合失調症、抑うつおよび双極性気分障害、不安障害、全般性不安障害、パニック、心的外傷後ストレス、恐怖症、急性ストレス、パラノイア、強迫性障害、食欲不振、過食症、人格障害、成長障害、性機能不全、物質関連障害、ならびに衝動制御障害からなる群から選択されることを特徴とする、前記〔4〕に記載の使用される化合物。
〔6〕治療がなされる神経疾患、障害または状態が、てんかん、アルツハイマー病、認知障害、記憶欠損、パーキンソン病、エイズ関連認知症、卒中などの無酸素性虚血性損傷、注意欠陥/多動性障害、振戦せん妄、神経変性、神経毒性、脆弱X、筋委縮性側索硬化症、ハンチントン舞踏病、自閉症、精神遅滞、ダウン症候群、および頭部外傷からなる群から選択されることを特徴とする、前記〔4〕に記載の使用される化合物。
〔7〕治療がなされる疼痛疾患、障害または状態が、慢性片頭痛、急性片頭痛、神経痛、ヘルペス後神経痛、三叉神経痛、化学療法誘発性ニューロパシー、炎症性疼痛、神経因性疼痛、糖尿病性ニューロパシー、関節炎、リウマチ様疾患、腰痛、術後疼痛、アンギナ、月経、痛風、腎疝痛および胆道疝痛に関連した疼痛からなる群から選択されることを特徴とする、前記〔4〕に記載の使用される化合物。
Claims (7)
- 医薬を調製するための、請求項1に記載の化合物の使用。
- 少なくとも1種の請求項1に記載の化合物またはその医薬品として許容される塩を含む、医薬品組成物。
- 精神医学的疾患若しくは障害;神経疾患若しくは障害;または疼痛疾患、障害もしくは状態の治療のための、請求項1に記載の化合物またはその医薬品として許容される塩を含有する医薬品組成物。
- 治療がなされる精神医学的疾患又は障害が、精神障害、統合失調症、抑うつおよび双極性気分障害、不安障害、全般性不安障害、パニック、心的外傷後ストレス、恐怖症、急性ストレス、パラノイア、強迫性障害、食欲不振、過食症、人格障害、成長障害、性機能不全、物質関連障害、ならびに衝動制御障害からなる群から選択されることを特徴とする、請求項4に記載の医薬品組成物。
- 治療がなされる神経疾患又は障害が、てんかん、アルツハイマー病、認知障害、記憶欠損、パーキンソン病、エイズ関連認知症、卒中などの無酸素性虚血性損傷、注意欠陥/多動性障害、振戦せん妄、神経変性、神経毒性、脆弱X、筋委縮性側索硬化症、ハンチントン舞踏病、自閉症、精神遅滞、ダウン症候群、および頭部外傷からなる群から選択されることを特徴とする、請求項4に記載の医薬品組成物。
- 治療がなされる疼痛疾患、障害または状態が、慢性片頭痛、急性片頭痛、神経痛、ヘルペス後神経痛、三叉神経痛、化学療法誘発性ニューロパシー、炎症性疼痛、神経因性疼痛、糖尿病性ニューロパシー、関節炎、リウマチ様疾患、腰痛、術後疼痛、アンギナ、月経、痛風、腎疝痛および胆道疝痛に関連した疼痛からなる群から選択されることを特徴とする、請求項4に記載の医薬品組成物。
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