JP2009504581A - アデニン誘導体 - Google Patents
アデニン誘導体 Download PDFInfo
- Publication number
- JP2009504581A JP2009504581A JP2008525416A JP2008525416A JP2009504581A JP 2009504581 A JP2009504581 A JP 2009504581A JP 2008525416 A JP2008525416 A JP 2008525416A JP 2008525416 A JP2008525416 A JP 2008525416A JP 2009504581 A JP2009504581 A JP 2009504581A
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- JP
- Japan
- Prior art keywords
- purine
- pyrrolidin
- salts
- cancer
- chlorophenoxymethyl
- 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.)
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- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
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Abstract
【化1】
Description
本発明は、有益な特性を有する新規化合物、特に医薬品の調製に使用可能な化合物を見出す目的に基づいてなされた。
熱ショックタンパク質(HSP)
ある組織の細胞は、例えば、熱、低酸素症、酸化的ストレス、または重金属やアルコールなどの有毒物質などの外部ストレスに反応し、「熱ショックタンパク質」(HSP)の名称で知られている幾つかのシャペロンを活性化する。HSPの活性化は、該細胞を、このようなストレス因子によって生じる損傷から保護し、生理状態の回復を促進し、細胞のストレス耐性状態をもたらす。外部ストレスに対してHSPによって促進される最初に発見されたこの防御機構以外に、ストレスのない正常条件下の個々のHSPについても、さらなる重要なシャペロン機能に次第に説明がつくようになってきた。したがって様々なHSPは、例えば、細胞の幾つかの生物学的に重要なタンパク質の正しい折り畳み、細胞内局在性および機能、または調節された分解を調節する。
HSP90は、全細胞タンパク質質量の約1〜2%に相当する。HSP90は、通常、細胞内では二量体の形態であり、いわゆるコシャペロンと言われる非常に多くのタンパク質と関連している(例えば、Pratt、1997参照)。HSP90は、細胞の活力にとって必須であり(Youngら、2001)、例えば熱ショックなどの外部ストレスによって生来の折り畳みが変質した多くのタンパク質と相互作用して、元の折り畳みを修復し、またはタンパク質の凝集を防止することによって、細胞ストレスに対する応答において重要な役割を担っている(Smithら、1998)。HSP90が、恐らくは突然変異によって引き起こされた誤ったタンパク質の折り畳みを修正することから、突然変異作用に対する緩衝剤として重要であるという指標もある(RutherfordおよびLindquist、1998)。さらにHSP90は、調節上の重要性も有する。HSP90は、生理条件下において、小胞体のその相同体であるGRP94と共にコンホメーションの安定性を確実にし、様々なクライアントキータンパク質を成熟させるために、細胞バランスに役割を担っている。これらは、ステロイドホルモンの受容体と、Ser/Thrまたはチロシンキナーゼ(例えば、ERBB2、RAF−1、CDK4、およびLCK)と、例えば特異型p53またはテロメラーゼhTERTの触媒サブユニットなどの様々なタンパク質の一群の3つのグループに分けることができる。これらのタンパク質のそれぞれは、細胞の生理的過程および生化学的過程の調節に重要な役割を持っている。ヒトにおいて保存されたHSP90ファミリーは、細胞質HSP90α、誘発性HSP90βアイソフォーム(Hickeyら、1989)、小胞体のGRP94(Argonら、1999)、およびミトコンドリアマトリックス内のHSP75/TRAP1(Feltsら、2000)の4つの遺伝子からなる。ファミリーの全メンバーは類似の作用機序を有しているが、細胞内のそれらの局在性に依存して、異なるクライアントタンパク質に結合すると推測される。例えば、ERBB2は、GRP94の特異的クライアントタンパク質であるが(Argonら、1999)、腫瘍壊死因子のタイプ1受容体(TNFR1)または網膜芽細胞腫タンパク質(Rb)は、TRAP1のクライアントであることが判明している(Songら、1995;Chenら、1996)。HSP90は、多数のクライアントタンパク質および調節タンパク質との幾つかの複雑な相互作用に関与している(Smith、2001)。正確な分子詳細は未だ明らかになっていないが、生化学的実験および研究と共に最近のX線結晶学を活用することによって、HSP90のシャペロン機能の詳細を解読できるようになってきた(Prodromouら、1997;Stebbinsら、1997)。したがって、HSP90は、ATP依存性分子のシャペロンであり(Prodromouら、1997)、ATP加水分解にとって二量化が重要となっている。ATPの結合の結果、トロイダル二量体構造が形成され、その2つのN末端ドメインは互いに密接し、コンホメーションのスイッチとして作用する(ProdromouおよびPearl、2000)。
最初に発見されたHSP90阻害剤のクラスは、ベンゾキノンアンサマイシンと、化合物ハービマイシンAおよびゲルダナマイシンであった。当初、それらと共に、v−Src癌遺伝子での形質転換によって誘発された線維芽細胞における悪性表現型の復帰が検出された(Ueharaら、1985)。
治療標的としてのHSP90
HSP90が、腫瘍表現型に非常に重要な多数のシグナル経路の調節に関与していることと、HSP90活性の阻害によって、幾つかの天然産物がそれらの生物学的作用を発揮するという発見とに起因して、HSP90は、腫瘍治療剤の開発のための新規標的として現在試験下にある(Neckersら、1999)。
WO2005/034950およびWO2005/021552には、HSP90阻害剤としての他のピリドチオフェン誘導体が記載されている。WO2005/00300A1には、HSP90阻害剤としてのトリアゾール誘導体が記載されている。WO00/53169には、クマリンまたはクマリン誘導体を用いたHSP90の阻害が記載されている。WO03/041643A2には、HSP90阻害性ゼアララノール誘導体が開示されている。WO2004/050087A1およびWO2004/056782A1には、3位または5位において芳香族基で置換されているHSP90阻害性ピラゾール誘導体が開示されている。WO03/055860A1には、HSP90阻害剤としての3,4−ジアリールピラゾールが記載されている。WO02/36075A2には、HSP90阻害特性を有するプリン誘導体が開示されている。
本発明は、式Iの化合物
Xは、CH2またはCOを示し、
Yは、O、S、NH(CH2)n、またはCH2を示し、
R1は、H、A、またはHalを示し、
R2は、ArまたはHetを示し、
R3は、H、A、OA、O(CH)nC≡CH、O(CH)nCH=CH2、O(CH)nCN、OH、SA、SH、Hal、NO2、CN、(CH2)nOH、O(CH2)nOH、(CH2)nOA、O(CH2)nOA、(CH2)nCOOH、O(CH2)nCOOH、(CH2)nCOOA、O(CH2)nCOOA、(CH2)nNH2、O(CH2)mNH2、(CH2)nNHA、O(CH2)mNHA、(CH2)nNAA’、O(CH2)mNAA’、(CH2)nCOA、O(CH2)nCOA、(CH2)nCONH2、O(CH2)nCONH2、(CH2)nCONHA、O(CH2)nCONHA、(CH2)nCONAA’、O(CH2)nCONAA’、(CH2)nNHCOA、O(CH2)mNHCOA、(CH2)nNHSO2A、O(CH2)mNHSO2A、(CH2)nNASO2A、O(CH2)mNASO2A、(CH2)nNHCONH2、O(CH2)mNHCONH2、(CH2)nNHCONH2、O(CH2)mNACONH2、(CH2)nNHCONHA、O(CH2)mNHCONHA、(CH2)nNACONHA、O(CH2)mNACONHA、(CH2)nNHCONAA’、O(CH2)mNHCONAA’、(CH2)nNACONAA’、O(CH2)mNACONAA’、O(CH2)pCH(OH)(CH2)pOHまたは(CH2)pCH(OH)(CH2)pOHを示し、
A、A’は、それぞれ互いに独立に、1〜5個のH原子がF、Cl、および/またはBrで置換されていてもよい、1〜10個のC原子を有する非分岐鎖または分岐鎖のアルキル、Alk、あるいは3〜7個のC原子を有する環状アルキルを示し、
AおよびA’はまた、一緒になって、2、3、4、5、または6個のC原子を有するアルキレン鎖を示し、ここで1個または2個のCH2基は、O、S、SO、SO2、NH、NA、および/またはN−COOAで置換されていてもよく、
Alkは、2〜6個のC原子を有するアルケニルを示し、
Arは、フェニル、ナフチル、またはビフェニルを示し、そのそれぞれは非置換であるか、あるいはA、OA、OH、SH、SA、Hal、NO2、CN、(CH2)nAr’、(CH2)nCOOH、(CH2)nCOOA、CHO、COA、SO2A、CONH2、SO2NH2、CONHA、CONAA’、SO2NHA、SO2NAA’、NH2、NHA、NAA’、OCONH2、OCONHA、OCONAA’、NHCOA、NHCOOA、NACOOA、NHSO2OA、NASO2OA、NHCONH2、NACONH2、NHCONHA、NACONHA、NHCONAA’、NACONAA’、NHCO(CH2)nNH2および/または−O−(CH2)o−Het1で、一置換、二置換、三置換、四置換、または五置換されており、
Ar’は、フェニル、ナフチル、またはビフェニルを示し、そのそれぞれは非置換であるか、あるいはA、OA、OH、SH、SA、Hal、NO2、CN、(CH2)nフェニル、(CH2)nCOOH、(CH2)nCOOA、CHO、COA、SO2A、CONH2、SO2NH2、CONHA、CONAA’、SO2NHA、SO2NAA’、NH2、NHA、NAA’、OCONH2、OCONHA、OCONAA’、NHCOA、NHCOOA、NACOOA、NHSO2OA、NASO2OA、NHCONH2、NACONH2、NHCONHA、NACONHA、NHCONAA’および/またはNACONAA’で一置換、二置換、または三置換されており、
Hetは、1〜4個のN、O、および/またはS原子を有する、単環式または二環式の、飽和、不飽和、または芳香族複素環を示し、A、OA、OH、SH、SA、Hal、NO2、CN、(CH2)nAr’、(CH2)nCOOH、(CH2)nCOOA、CHO、COA、SO2A、CONH2、SO2NH2、CONHA、CONAA’、SO2NHA、SO2NAA’、NH2、NHA、NAA’、OCONH2、OCONHA、OCONAA’、NHCOA、NHCOOA、NACOOA、NHSO2OA、NASO2OA、NHCONH2、NACONH2、NHCONHA、NACONHA、NHCONAA’、NACONAA’、SO2A、=S、=NH、=NAおよび/または=O(カルボニル酸素)で一置換、二置換、または三置換されていてもよく、
Het1は、1〜2個のNおよび/またはO原子を有する単環式飽和複素環を示し、A、OA、OH、Hal、および/または=O(カルボニル酸素)で一置換または二置換されていてもよく、
Halは、F、Cl、Br、またはIを示し、
mは、2、3、4、5、または6を示し、
nは、0、1、2、3、または4を示し、
oは、1または2を示し、
pは、1、2、3、または4を示す]、
ならびにそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物に関する。
式IIの化合物
X、Y、R2、およびR3は、請求項1に記載の意味を有する)
を、式IIIの化合物
と反応させ、
かつ/または式Iの塩基もしくは酸が、それらの塩の1つに変換されることを特徴とする。
Iaにおいて、Yは、OまたはNH(CH2)nを示し、
Ibにおいて、R3は、H、A、OA、OH、O(CH)nC≡CH、O(CH)nCH=CH2、または(CH2)pCH(OH)(CH2)pOHを示し、
Icにおいて、Arは、非置換のフェニル、またはA、Hal、OA、OH、またはCNで一置換、二置換、三置換、四置換、または五置換されているフェニルを示し、
Idにおいて、Hetは、A、OA、および/またはHalで一置換、二置換、または三置換されていてもよい、1〜3個のN原子を有する単環式芳香族複素環を示し、
Ieにおいて、Aは、1〜5個のH原子がFおよび/またはClで置換されていてもよい、1〜6個のC原子を有する非分岐鎖または分岐鎖のアルキル、あるいはAlkを示し、
Ifにおいて、Xは、CH2またはCOを示し、
Yは、OまたはNH(CH2)nを示し、
R1は、H、A、またはHalを示し、
R2は、ArまたはHetを示し、
R3は、H、A、OA、OH、O(CH)nC≡CH、O(CH)nCH=CH2、または(CH2)pCH(OH)(CH2)pOHを示し、
Aは、1〜5個のH原子がFおよび/またはClで置換されていてもよい、1〜6個のC原子を有する非分岐鎖または分岐鎖のアルキル、あるいはAlkを示し、
Alkは、2〜6個のC原子を有するアルケニルを示し、
Arは、非置換のフェニル、またはA、Hal、OA、OH、もしくはCNで一置換、二置換、三置換、四置換、もしくは五置換されているフェニルを示し、
Hetは、A、OA、および/またはHalで一置換、二置換、または三置換されていてもよい、1〜3個のN原子を有する単環式芳香族複素環を示し、
Halは、F、Cl、Br、またはIを示し、
pは、1、2、3、または4を示し、
nは、0、1、または2を示す。
本発明の前記化合物は、塩ではないそれらの最終形態で使用することができる。一方、本発明は、かかる化合物をそれらの医薬品として許容される塩の形態で使用することも包含し、それらは当技術分野に知られている手順によって、様々な有機酸および無機酸ならびに塩基から誘導することができる。式Iの化合物の医薬品として許容される塩の形態は、その大部分が通常の方法によって調製される。式Iの化合物がカルボキシル基を含む場合、その適切な塩の1つは、該化合物を適切な塩基と反応させて、対応する塩基付加塩を得ることによって形成することができる。このような塩基は、例えば、水酸化カリウム、水酸化ナトリウム、および水酸化リチウムを含めたアルカリ金属水酸化物、アルカリ土類金属水酸化物、例えば、水酸化バリウムおよび水酸化カルシウム、アルカリ金属アルコキシド、例えば、カリウムエトキシドおよびナトリウムプロポキシド、ならびに様々な有機塩基、例えば、ピペリジン、ジエタノールアミン、およびN−メチルグルタミンである。式Iの化合物のアルミニウム塩も同様に含まれる。式Iの幾つかの化合物の場合において、酸付加塩は、これらの化合物を医薬品として許容される有機酸および無機酸で、例えばハロゲン化水素、例えば塩化水素、臭化水素、またはヨウ化水素、他の鉱酸および対応するそれらの塩、例えば硫酸塩、硝酸塩、またはリン酸塩等、ならびにアルキル−およびモノアリールスルホン酸塩、例えばエタンスルホン酸塩、トルエンスルホン酸塩、およびベンゼンスルホン酸塩、ならびに他の有機酸および対応するそれらの塩、例えば酢酸塩、トリフルオロ酢酸塩、酒石酸塩、マレイン酸塩、コハク酸塩、クエン酸塩、安息香酸塩、サリチル酸塩、アスコルビン酸塩等で処理することによって形成することができる。したがって、式Iの化合物の医薬品として許容される酸付加塩には、以下の、酢酸塩、アジピン酸塩、アルギン酸塩、アルギネート(arginate)、アスパラギン酸塩、安息香酸塩、ベンゼンスルホン酸塩(ベシラート)、重硫酸塩、亜硫酸水素塩、臭化物、酪酸塩、樟脳酸塩、カンファースルホン酸塩、カプリル酸塩、塩化物、クロロ安息香酸塩、クエン酸塩、シクロペンタンプロピオン酸塩、ジグルコン酸塩、二水素リン酸塩、ジニトロ安息香酸塩、ドデシル硫酸塩、エタンスルホン酸塩、フマル酸塩、ガラクタル酸塩(粘液酸由来)、ガラクツロン酸塩、グルコヘプタン酸塩、グルコン酸塩、グルタミン酸塩、グリセロリン酸塩、ヘミコハク酸塩、ヘミ硫酸塩、ヘプタン酸塩、ヘキサン酸塩、馬尿酸塩、塩酸塩、臭化水素酸塩、ヨウ化水素酸塩、2−ヒドロキシエタンスルホン酸塩、ヨウ化物、イセチオン酸塩、イソ酪酸塩、乳酸塩、ラクトビオン酸、リンゴ酸塩、マレイン酸塩、マロン酸塩、マンデル酸塩、メタリン酸塩、メタンスルホン酸塩、メチル安息香酸塩、リン酸一水素塩、2−ナフタレンスルホン酸塩、ニコチン酸塩、硝酸塩、シュウ酸塩、オレイン酸塩、パモ酸塩、ペクチン酸塩、過硫酸塩、フェニル酢酸塩、3−フェニルプロピオン酸塩、リン酸塩、ホスホン酸塩、フタル酸塩が含まれるが、これらに限定されるものではない。
(a)有効量の式Iの化合物、ならびに/あるいはそれらの医薬品として有用な誘導体、溶媒和物、および立体異性体、ならびにあらゆる比のそれらの混合物と、
(b)有効量の追加の医薬品有効成分と
の個別包装からなる一組(キット)に関する。
使用
本発明の化合物は、HSP90が役割を担う疾患の治療における、哺乳類動物、特にヒトのための医薬品有効成分として適している。
;ウィルス性病原体が、A型肝炎、B型肝炎、C型肝炎、インフルエンザ、水痘、アデノウィルス、単純ヘルペスI型(HSV−I)、単純ヘルペスII型(HSV−II)、牛疫、ライノウィルス、エコーウィルス、ロタウィルス、呼吸器合胞体ウィルス(RSV)、パピローマウィルス、パポバウィルス、サイトメガロウィルス、エキノウィルス、アルボウィルス、ハンタウィルス、コクサッキーウィルス、ムンプスウィルス、麻疹ウィルス、風疹ウィルス、ポリオウィルス、I型ヒト免疫不全ウィルス(HIV−I)、およびII型ヒト免疫不全ウィルス(HIV−II)からなる群から選択されるウィルス性疾患;移植体における免疫抑制;炎症誘発性疾患、例えば、関節リウマチ(rheumatoid arthritis)、喘息(asthma)、多発性硬化症(multiple sclerosis)、1型糖尿病(type 1 diabetes)、紅斑性狼瘡(lupus erythematosus)、乾癬(psoriasis)、および炎症性大腸炎(innammatory bowel disease);嚢胞性線維症(cystic fibrosis);血管新生(angiogenesis)に関連する疾患、例えば、糖尿病性網膜症(diabetic retinopathy)、血管腫(haemangioma)、子宮内膜症(endometriosis)、腫瘍血管新生(tumour angiogenesis)など;感染症(infectious diseases);自己免疫疾患(autoimmune diseases);虚血(ischaemia);神経再生促進(promotion of nerve regeneration);線維形成性疾患(fibrogenetic diseases)、例えば硬化性皮膚炎(sclerodermatitis)、多発性筋炎(polymyositis)、全身性紅斑性狼瘡(systemic lupus)、肝硬変(cirrhosis of the Iiver)、ケロイド形成(keloid formation)、間質性腎炎(interstitial nephritis)、および肺線維症(pulmonary fibrosis)などの治療のための医薬品の調製に使用することが好ましい。
の結果生じる。
HSP90阻害性を測定するための試験方法
ゲルダナマイシンまたは17−アリルアミノ−17−デメトキシゲルダナマイシン(17AAG)のHSP90との結合、ならびにその競合阻害を利用して、本発明の化合物の阻害活性を決定することができる(Carrerasら、2003、Chiosisら、2002)。特定の場合には、放射性リガンドフィルター結合試験を使用する。ここで使用される放射性リガンドは、トリチウム標識17−アリルアミノゲルダナマイシン、[3H]17AAGである。このフィルター結合試験によって、ATP結合部位を妨害する阻害剤を標的とする研究が可能となる。
材料
組換えヒトHSP90α(E.coil発現、95%純度)
[3H]17AAG(17−アリルアミノゲルダナマイシン、[アリルアミノ−2,3−3H。比放射能:1.11x1012Bq/mmol(Moravek、MT−1717)
HEPESフィルター緩衝剤(50mMのHEPES、pH7.0、5mMのMgCl2、BSA0.01%)
マルチスクリーンFB(1μm)フィルタープレート(Millipore、MAFBNOB50)
方法
まず、96ウェルマイクロタイターフィルタープレートを洗浄し、0.1%のポリエチレンイミンで被覆する。
反応温度22℃
反応時間:30分、800rpmで振とう
試験体積:50μl
最終濃度:
50mMのHEPES HCI、pH7.0、5mMのMgCl2、0.01%(w/v)BSA
HSP90:1.5μg/アッセイ
[3H]17AAG:0.08μM
反応の終了時に、フィルタープレートの上清を、真空マニホールド(Multiscreen Separation System、Millipore)を利用して吸引除去し、そのフィルターを2回洗浄する。次いでフィルタープレートを、βカウンター(Microbeta、Wallac)中、シンチレーター(Microscint20、Packard)で測定する。
LC−MS条件
以下の、イオン源エレクトロスプレー(正モード)、走査100〜1000m/e、フラグメント電圧60V、ガス温度300℃、DAD220nmの特徴を有するHP1100シリーズHewlett Packard System。
カラム:Chromolith SpeedROD RP−18e 50−4.6
溶媒:Merck KGaA製LiChrosolvグレード
勾配
P1:溶媒A:H2O(0.1%TFA)
溶媒B:ACN(0.1%TFA)
99%A→100%B:ランタイム6分/流量3.0ml/分
P2:溶媒A:H2O(0.01%TFA)
溶媒B:ACN(0.01%TFA)
99%A→100%B:ランタイム5分/流量2.75ml/分
N:溶媒A:H2O(0.01%TFA)
溶媒B:ACN(0.01%TFA)
90%A→100%B:ランタイム5分/流量2.75ml/分
以下の実施例で示される保持時間RT[分]およびM+H+データMWは、LC−MS測定の測定結果である。
6−[(R)−2−(5−フルオロ−2−メトキシフェノキシメチル)ピロリジン−1−イル]−9H−プリン(「A1」)の調製
1.1 反応を、窒素雰囲気下で実施する。トリエチルアミン151mlに続いてtert−ブタノール300mlを、(R)−プロリンメチルエステル83.77gのtert−ブタノール600ml中溶液に添加する。次いで、二炭酸ジ−tert−ブチル[(BOC)2O]96.03gのtert−ブタノール100ml中溶液を滴加し、その混合液を室温で20時間撹拌する。堆積した沈殿物を分離する。生成物をろ液に入れる。溶媒を除去し、残渣をジエチルエーテル700mlに溶解する。溶液を、1NのHCl500mlで2回、飽和Na2CO3溶液500mlで1回、および飽和NaCl溶液500mlで1回洗浄する。Na2SO4で乾燥させた後、溶媒を除去し、BOC−(R)−プロリンメチルエステル(「1」)86.7gを黄色油として得る。
さらなる中間化合物の調製
A−1 トリエチルアミン247.9μlを、「2」300mgのジクロロメタン5ml中溶液に添加し、次いで塩化メタンスルホニル127.1μlを滴加し、混合液を室温でさらに45分間撹拌する。通常の後処理によって、(R)−2−メタンスルホニルオキシメチル−N−BOC−ピロリジン(「3」)392mgを得る。
6−[(R)−2−(4−クロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン(「A2」)の調製
2.1 実施例1.3と同様に、「2」および4−クロロフェノールによって、化合物(R)−2−(4−クロロフェノキシメチル)−N−BOC−ピロリジン(「7」)を得る。
6−[(R)−2−(3,4−ジフルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン(「A3」)の調製
3.1 実施例1.3と同様に、「2」および3,4−ジフルオロフェノールによって、化合物(R)−2−(3,4−ジフルオロフェノキシメチル)−N−BOC−ピロリジン(「9」)を得る。
6−[(R)−2−(2−メトキシフェノキシメチル)ピロリジン−1−イル]−9H−プリン(「A16」)の調製
4.1 「3」75mg、2−メトキシフェノール58.99μl、および炭酸セシウム87.3mgのDMF1.5ml中混合液を、100℃で16時間撹拌する。混合液を、水10mlで希釈し、酢酸エチルで3回抽出する。各有機相を混合し、さらに通常の後処理にかけ、(R)−2−(2−メトキシフェノキシメチル)−N−BOC−ピロリジン(「11」)63.7mgを得る。
6−{(R)−2−[(2−フルオロフェニルアミノ)メチル]ピロリジン−1−イル}−9H−プリン(「A31」)の調製
5.1 トリアセトキシ水素化ホウ素ナトリウム82.24mgを、0℃で、「4」50mgおよび2−フルオロアニリン26.67μlのジクロロメタン1ml中混合液に添加する。その混合液を室温に加熱し、さらに16時間撹拌する。反応混合液をシリカゲルでクロマトグラフし、(R)−2−[(2−フルオロフェニルアミノ)メチル]−N−BOC−ピロリジン(「13」)30.9mgを得る。
6−{(R)−2−[(フェニルアミノ)メチル]ピロリジン−1−イル}−9H−プリン(「A32」)、HPLC保持時間2.54分、勾配P2、[M+H]+295。
6−{(R)−2−[(2−クロロフェニルアミノ)メチル]ピロリジン−1−イル}−9H−プリン(「A33」)、HPLC保持時間2.78分、勾配P2、[M+H]+329。
6−{(R)−2−[(2−クロロフェニルアミノ)カルボニル]ピロリジン−1−イル}−9H−プリン(「A34」)の調製
6.1 まず、BOC−D−プロリン150mgおよびトリフェニルホスフィン(ポリマー結合)696.87mgを、フリットを備えた8mlのプラスチックシンブルに入れ、ジクロロメタン4mlを添加し、その混合液を5分間振とうする。次いで、トリクロロアセトニトリル139.75μlを滴加し、その混合液を室温でさらに4時間振とうする。その後、フリットを介して反応溶液をろ過し、2−クロロアニリン73.48μl、モルホリノメチル−ポリスチレン597.3mg、およびジクロロメタン1mlを入れた第2の(12ml)プラスチックシンブルに直接入れる。混合液を室温でさらに16時間撹拌する。次いで混合液をろ過し、ろ液を蒸発させ、残渣をRP18カラムでクロマトグラフする。通常の後処理によって、(R)−2−[(2−クロロフェニルアミノ)カルボニル]−N−BOC−ピロリジン(「15」)14.3mgを得る。
6−{(R)−2−[(2−フルオロフェニルアミノ)カルボニル]ピロリジン−1−イル}−9H−プリン(「A35」)、HPLC保持時間2.51分、勾配P2、[M+H]+327。
7.1 トリエチルアミン93.84μlを、(R)−2−(2−クロロフェノキシメチル)ピロリジントリフルオロ酢酸75mgおよび2−アミノ−6−クロロ−9H−プリン39.5mgのn−ブタノール1ml中混合液に滴加する。反応混合液を100℃で2.5時間撹拌する。その混合液を冷却し、堆積した沈殿物を分離し、ろ液をRP18カラム12gで直接クロマトグラフする。単離した生成物の画分を通常の精製にかけ、2−アミノ−6−[(R)−2−(2−クロロフェノキシメチル)−ピロリジン−1−イル]−9H−プリン(「A36」)45.4mgを得る。HPLC保持時間2.77分、勾配P2、[M+H]+345。
8.1 「3」100mg、2−フルオロフェノール50.3μl、炭酸セシウム116.6mg、およびDMF2mlの混合液を、100℃で16時間撹拌する。通常の後処理によって、(R)−2−(2−フルオロフェノキシメチル)−N−BOC−ピロリジン49.5mgを得る。
9.1 エチル(R)−5−オキソピロリジン−2−カルボキシラート1.0g、ベンジルクロロホルメート949.8μ1、ビス(トリメチルシリル)リチウムアミド6.9ml(THF中)のTHF25ml中の標準条件下での反応、ならびに後処理によって、エチル(R)−5−オキソ−N−ベンジルオキシカルボニルピロリジン−2−カルボキシラート(「17」)730mgを得る。
以下の化合物は、実施例6と同様にして得られる。
以下の化合物は、実施例1と同様にして得られる。
2−クロロ−6−[(2R,4S)−2−(2−クロロフェノキシメチル)−4−プロプ−2−イニルオキシピロリジン−1−イル]−9H−プリン(「A48」)の調製
6−[(2R,4S)−2−(2−クロロフェノキシメチル)−4−プロプ−2−イニルオキシピロリジン−1−イル]−9H−プリン(「A49」)、保持時間2.95分、勾配HPLC P2、[M+H]+384、
2−クロロ−6−[(2R,4S)−2−(2−クロロフェノキシメチル)−4−アリルオキシピロリジン−1−イル]−9H−プリン(「A50」)、保持時間3.51分、勾配HPLC P2、[M+H]+421、
6−[(2R,4S)−2−(2−クロロフェノキシメチル)−4−アリルオキシピロリジン−1−イル]−9H−プリン(「A51」)、保持時間3.01分、勾配HPLC P2、[M+H]+386、
2−クロロ−6−[(2R,4S)−2−フェノキシメチル−4−ヒドロキシピロリジン−1−イル]−9H−プリン(「A53」)、保持時間2.92分、勾配HPLC P2、[M+H]+346、
2−クロロ−6−[(2R,4S)−2−(2−フルオロフェノキシメチル)−4−ヒドロキシピロリジン−1−イル]−9H−プリン(「A54」)、保持時間2.93分、勾配HPLC P2、[M+H]+365、
2−クロロ−6−[(2R,4S)−2−(2−フルオロフェノキシメチル)−4−プロプ−2−イニルオキシピロリジン−1−イル]−9H−プリン(「A55」)、保持時間3.29分、勾配HPLC P2、[M+H]+402、
2−クロロ−6−[(2R,4S)−2−フェノキシメチル−4−プロプ−2−イニルオキシピロリジン−1−イル]−9H−プリン(「A56」)、保持時間3.28分、勾配HPLC P2、[M+H]+384。
DEI−MSフラグメントの解釈
化合物「A29」
本発明の有効成分100gおよびリン酸一水素二ナトリウム5gの再蒸留水3l中溶液を、2Nの塩酸を使用してpH6.5に調節し、滅菌ろ過し、注入バイアルに移し、滅菌条件下で凍結乾燥させ、滅菌条件下で封止する。各注入バイアルは、有効成分5mgを含有する。
本発明の有効成分20gと、大豆レシチン100gおよびココアバター1400gとの混合物を溶融し、成形型に注ぎ冷却する。各坐剤は、有効成分20mgを含有する。
溶剤は、再蒸留水940ml中、本発明の有効成分1g、NaH2PO4・2H2O9.38g、Na2HPO4・12H2O28.48g、および塩化ベンザルコニウム0.1gから調製する。pHを6.8に調節し、溶液を1lにし、放射線によって滅菌する。この溶液は、点眼剤の形態で使用することができる。
本発明の有効成分500mgを、無菌条件下でワセリン99.5gと混合する。
本発明の有効成分1kg、ラクトース4kg、ジャガイモデンプン1.2kg、タルク0.2kg、およびステアリン酸マグネシウム0.1kgの混合物を、通常のやり方で圧縮して、各錠剤が有効成分10gを含有するように錠剤を得る。
錠剤を実施例Eと同様に圧縮し、その後通常のやり方で、ショ糖、ジャガイモデンプン、タルク、トラガカント、および色素のコーティングで被覆する。
各カプセルが有効成分20mgを含有するように、本発明の有効成分2kgを通常のやり方で硬質ゼラチンカプセル剤に入れる。
本発明の有効成分1kgの再蒸留水60l中溶液を滅菌ろ過し、アンプルに移し、滅菌条件下で凍結乾燥させ、滅菌条件下で封止する。各アンプルは、有効成分10mgを含有する。
Claims (20)
- 式Iの化合物
Xは、CH2またはCOを示し、
Yは、O、S、NH(CH2)nまたはCH2を示し、
R1は、H、A、またはHalを示し、
R2は、ArまたはHetを示し、
R3は、H、A、OA、O(CH)nC≡CH、O(CH)nCH=CH2、O(CH)nCN、OH、SA、SH、Hal、NO2、CN、(CH2)nOH、O(CH2)nOH、(CH2)nOA、O(CH2)nOA、(CH2)nCOOH、O(CH2)nCOOH、(CH2)nCOOA、O(CH2)nCOOA、(CH2)nNH2、O(CH2)mNH2、(CH2)nNHA、O(CH2)mNHA、(CH2)nNAA’、O(CH2)mNAA’、(CH2)nCOA、O(CH2)nCOA、(CH2)nCONH2、O(CH2)nCONH2、(CH2)nCONHA、O(CH2)nCONHA、(CH2)nCONAA’、O(CH2)nCONAA’、(CH2)nNHCOA、O(CH2)mNHCOA、(CH2)nNHSO2A、O(CH2)mNHSO2A、(CH2)nNASO2A、O(CH2)mNASO2A、(CH2)nNHCONH2、O(CH2)mNHCONH2、(CH2)nNHCONH2、O(CH2)mNACONH2、(CH2)nNHCONHA、O(CH2)mNHCONHA、(CH2)nNACONHA、O(CH2)mNACONHA、(CH2)nNHCONAA’、O(CH2)mNHCONAA’、(CH2)nNACONAA’、O(CH2)mNACONAA’、O(CH2)pCH(OH)(CH2)pOHまたは(CH2)pCH(OH)(CH2)pOHを示し、
A、A’は、それぞれ互いに独立に、1〜5個のH原子がF、Cl、および/またはBrで置換されていてもよい、1〜10個のC原子を有する非分岐鎖または分岐鎖のアルキル、Alk、あるいは3〜7個のC原子を有する環状アルキルを示し、
AおよびA’はまた、一緒になって、2、3、4、5、または6個のC原子を有するアルキレン鎖を示し、ここで、1個または2個のCH2基は、O、S、SO、SO2、NH、NA、および/またはN−COOAで置換されていてもよく、
Alkは、2〜6個のC原子を有するアルケニルを示し、
Arは、フェニル、ナフチル、またはビフェニルを示し、そのそれぞれは非置換であるか、あるいはA、OA、OH、SH、SA、Hal、NO2、CN、(CH2)nAr’、(CH2)nCOOH、(CH2)nCOOA、CHO、COA、SO2A、CONH2、SO2NH2、CONHA、CONAA’、SO2NHA、SO2NAA’、NH2、NHA、NAA’、OCONH2、OCONHA、OCONAA’、NHCOA、NHCOOA、NACOOA、NHSO2OA、NASO2OA、NHCONH2、NACONH2、NHCONHA、NACONHA、NHCONAA’、NACONAA’、NHCO(CH2)nNH2および/または−O−(CH2)o−Het1で一置換、二置換、三置換、四置換、または五置換され、
Ar’は、フェニル、ナフチル、またはビフェニルを示し、そのそれぞれは非置換であるか、あるいはA、OA、OH、SH、SA、Hal、NO2、CN、(CH2)nフェニル、(CH2)nCOOH、(CH2)nCOOA、CHO、COA、SO2A、CONH2、SO2NH2、CONHA、CONAA’、SO2NHA、SO2NAA’、NH2、NHA、NAA’、OCONH2、OCONHA、OCONAA’、NHCOA、NHCOOA、NACOOA、NHSO2OA、NASO2OA、NHCONH2、NACONH2、NHCONHA、NACONHA、NHCONAA’および/またはNACONAA’で一置換、二置換、または三置換され、
Hetは、1〜4個のN、O、および/またはS原子を有する、単環式または二環式の飽和、不飽和、または芳香族複素環を示し、A、OA、OH、SH、SA、Hal、NO2、CN、(CH2)nAr’、(CH2)nCOOH、(CH2)nCOOA、CHO、COA、SO2A、CONH2、SO2NH2、CONHA、CONAA’、SO2NHA、SO2NAA’、NH2、NHA、NAA’、OCONH2、OCONHA、OCONAA’、NHCOA、NHCOOA、NACOOA、NHSO2OA、NASO2OA、NHCONH2、NACONH2、NHCONHA、NACONHA、NHCONAA’、NACONAA’、SO2A、=S、=NH、=NAおよび/または=O(カルボニル酸素)で一置換、二置換、または三置換されていてもよく、
Het1は、1〜2個のNおよび/またはO原子を有する単環式飽和複素環を示し、A、OA、OH、Hal、および/または=O(カルボニル酸素)で一置換または二置換されていてもよく、
Halは、F、Cl、Br、またはIを示し、
mは、2、3、4、5、または6を示し、
nは、0、1、2、3、または4を示し、
oは、1または2を示し、
pは、1、2、3、または4を示す]、
ならびにそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物。 - YがOまたはNH(CH2)nを示す、請求項1に記載の式Iの化合物、ならびにそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物。
- R3が、H、A、OA、OH、O(CH)nC≡CH、O(CH)nCH=CH2、または(CH2)pCH(OH)(CH2)pOHを示す、請求項1または2に記載の化合物、ならびにそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物。
- Arが、非置換のフェニル、またはA、Hal、OA、OH、もしくはCNで一置換、二置換、三置換、四置換、もしくは五置換されているフェニルを示す、請求項1から3の一項または複数項に記載の化合物、ならびにそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物。
- Hetが、A、OA、および/またはHalで一置換、二置換、または三置換されていてもよい、1〜3個のN原子を有する単環式芳香族複素環を示す、請求項1から4の一項または複数項に記載の化合物、ならびにそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物。
- Aが、1〜5個のH原子がFおよび/またはClで置換されていてもよい、1〜6個のC原子を有する非分岐鎖または分岐鎖のアルキル、あるいはAlkを示す、請求項1から12の一項または複数項に記載の化合物、ならびにそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物。
- Xが、CH2またはCOを示し、
Yが、OまたはNH(CH2)nを示し、
R1が、H、A、またはHalを示し、
R2が、ArまたはHetを示し、
R3が、H、A、OA、OH、O(CH)nC≡CH、O(CH)nCH=CH2、または(CH2)pCH(OH)(CH2)pOHを示し、
Aが、1〜5個のH原子がFおよび/またはClで置換されていてもよい、1〜6個のC原子を有する非分岐鎖または分岐鎖のアルキル、あるいはAlkを示し、
Alkが、2〜6個のC原子を有するアルケニルを示し、
Arが、非置換のフェニル、またはA、Hal、OA、OH、もしくはCNで一置換、二置換、三置換、四置換、もしくは五置換されているフェニルを示し、
Hetが、A、OA、および/またはHalで一置換、二置換、または三置換されていてもよい、1〜3個のN原子を有する単環式芳香族複素環を示し、
Halが、F、Cl、Br、またはIを示し、
pが、1、2、3、または4を示し、
nが、0、1、または2を示す
請求項1から6の一項または複数項に記載の化合物、ならびにそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物。 - 以下の群から選択される、請求項1に記載の化合物:
(実施例A1) 6−[(R)−2−(5−フルオロ−2−メトキシフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A2) 6−[(R)−2−(4−クロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A3) 6−[(R)−2−(3,4−ジフルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A4) 6−[(R)−2−(4−メチルフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A5) 6−[(R)−2−(ピリジン−2−イルオキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A6) 6−[(R)−2−(6−メチルピリジン−2−イルオキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A7) 6−[(R)−2−(2,5−ジフルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A8) 6−[(R)−2−(3,5−ジフルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A9) 6−[(R)−2−(2,4−ジフルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A10) 6−[(R)−2−(2−フルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A11) 6−[(R)−2−(3−フルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A12) 6−[(R)−2−(2,3−ジフルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A13) 6−[(R)−2−(4−メトキシフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A14) 6−[(R)−2−(4−シアノフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A15) 6−[(R)−2−(4−フルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A16) 6−[(R)−2−(2−メトキシフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A17) 6−[(R)−2−(2−エチルフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A18) 6−[(R)−2−(2−メチルフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A19) 6−[(R)−2−(フェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A20) 6−[(R)−2−(2−クロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A21) 6−[(R)−2−(2,3−ジクロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A22) 6−[(R)−2−(2−トリフルオロメチルフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A23) 6−[(R)−2−(2,4−ジクロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A24) 6−[(R)−2−(2−クロロ−5−メチルフェノキシメチル)ピロリジン−1−イル]−9H−プリン
(実施例A25) 6−[(R)−2−(2,6−ジクロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A26) 6−[(R)−2−(2,5−ジクロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A27) 6−[(R)−2−(2−クロロ−4−フルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A28) 6−[(R)−2−(2−クロロ−4−メトキシフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A29) 2−クロロ−6−[(R)−2−(2−クロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A30) 6−[(R)−2−(4−クロロピリジン−3−イルオキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A31) 6−{(R)−2−[(2−フルオロフェニルアミノ)メチル]ピロリジン−1−イル}−9H−プリン、
(実施例A32) 6−{(R)−2−[(フェニルアミノ)メチル]ピロリジン−1−イル}−9H−プリン、
(実施例A33) 6−{(R)−2−[(2−クロロフェニルアミノ)メチル]ピロリジン−1−イル}−9H−プリン、
(実施例A34) 6−{(R)−2−[(2−クロロフェニルアミノ)カルボニル]ピロリジン−1−イル}−9H−プリン、
(実施例A35) 6−{(R)−2−[(2−フルオロフェニルアミノ)カルボニル]ピロリジン−1−イル}−9H−プリン、
(実施例A36) 2−アミノ−6−[(R)−2−(2−クロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A37) 2−フルオロ−6−[(R)−2−(2−クロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A38) 2−クロロ−6−[(R)−2−(2−フルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A39) 6−[(2R,5R)−2−ブト−3−エニル−5−(2−クロロフェノキシ−メチル)ピロリジン−1−イル]−9H−プリン、
(実施例A40) 4−[(2S,5R)−5−(2−クロロフェノキシメチル)−1−(9H−プリン−6−イル)ピロリジン−2−イル]ブタン−1,2−ジオール、
(実施例A41) 3−[(2S,5R)−5−(2−クロロフェノキシメチル)−1−(9H−プリン−6−イル)ピロリジン−2−イル]プロパン−1−オール、
(実施例A42) 6−{(R)−2−[(2−フルオロベンジルアミノ)カルボニル]ピロリジン−1−イル}−9H−プリン、
(実施例A44) 6−[(S)−2−(2−クロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A45) 6−[(S)−2−(フェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A46) 6−[(S)−2−(2−メチルフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A47) 2−フルオロ−6−[(R)−2−(2−フルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A48) 2−クロロ−6−[(2R,4S)−2−(2−クロロフェノキシメチル)−4−プロプ−2−イニルオキシピロリジン−1−イル]−9H−プリン、
(実施例A49) 6−[(2R,4S)−2−(2−クロロフェノキシメチル)−4−プロプ−2−イニルオキシピロリジン−1−イル]−9H−プリン、
(実施例A50) 2−クロロ−6−[(2R,4S)−2−(2−クロロフェノキシメチル)−4−アリルオキシピロリジン−1−イル]−9H−プリン、
(実施例A51) 6−[(2R,4S)−2−(2−クロロフェノキシメチル)−4−アリルオキシ−ピロリジン−1−イル]−9H−プリン、
(実施例A52) 6−[(R)−2−(2−ブロモフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A53) 2−クロロ−6−[(2R,4S)−2−フェノキシメチル−4−ヒドロキシ−ピロリジン−1−イル]−9H−プリン、
(実施例A54) 2−クロロ−6−[(2R,4S)−2−(2−フルオロフェノキシメチル)−4−ヒドロキシピロリジン−1−イル]−9H−プリン、
(実施例A55) 2−クロロ−6−[(2R,4S)−2−(2−フルオロフェノキシメチル)−4−プロプ−2−イニルオキシピロリジン−1−イル]−9H−プリン、
(実施例A56) 2−クロロ−6−[(2R,4S)−2−フェノキシメチル−4−プロプ−2−イニルオキシ−ピロリジン−1−イル]−9H−プリン、
(実施例A57) 2−メチル−6−[(R)−2−(2−フルオロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A58) 2−メチル−6−[(R)−2−(2−クロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
(実施例A59) 6−[(R)−2−(2−クロロフェノキシメチル)ピロリジン−1−イル]−9H−プリン、
ならびにそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物。 - 少なくとも1種の式Iの化合物、ならびに/あるいはそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物、ならびに任意選択で賦形剤および/または助剤を含む医薬品。
- 式Iの化合物、ならびにそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物の、HSP90の阻害、調節、および/または調整が役割を担う疾患の治療および/または予防のための医薬品を調製するための使用。
- 腫瘍疾患、ウィルス性疾患の治療または予防のため、移植体における免疫抑制、炎症誘発性疾患、嚢胞性線維症、血管新生に関連する疾患、感染症、自己免疫疾患、虚血、線維形成性疾患のため、神経再生促進のため、癌細胞、腫瘍細胞の増殖、および腫瘍転移を阻害するため、化学療法によって生じる毒性から正常細胞を保護するため、誤ったタンパク質の折り畳みまたは凝集が主な原因因子である疾患の治療のための医薬品を調製するための、式Iの化合物、ならびにそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物の請求項11に記載の使用。
- 前記腫瘍疾患が、線維肉腫、粘液肉腫、脂肪肉腫、軟骨肉腫、骨肉腫、脊索腫、血管肉腫、内皮腫、リンパ管肉腫、リンパ管内皮肉腫、滑膜腫、中皮腫、ユーイング腫瘍、平滑筋肉腫、横紋筋肉腫、結腸癌、膵臓癌、乳癌、卵巣癌、前立腺癌、扁平上皮細胞癌、基底細胞癌、腺癌、汗腺癌、脂腺癌、乳頭状癌、乳頭状腺癌、嚢胞腺癌、骨髄癌、気管支癌、腎細胞癌、肝臓癌、胆管癌、絨毛癌、セミノーマ、胚性癌腫、ウィルムス腫瘍、子宮頸癌、睾丸腫瘍、肺癌、小細胞肺癌、膀胱癌、上皮癌、神経膠腫、星状細胞腫、髄芽腫、頭蓋咽頭腫、上衣腫、松果体腫、血管芽腫、聴神経腫、乏突起膠腫、髄膜腫、黒色腫、神経芽細胞腫、網膜芽細胞腫、白血病、リンパ腫、多発性骨髄腫、ワルデンシュトレーム型マクログロブリン血症、および重鎖病である、請求項12に記載の使用。
- 前記ウィルス性疾患のウィルス性病原体が、A型肝炎、B型肝炎、C型肝炎、インフルエンザ、水痘、アデノウィルス、単純ヘルペスI型(HSV−I)、単純ヘルペスII型(HSV−II)、牛疫、ライノウィルス、エコーウィルス、ロタウィルス、呼吸器合胞体ウィルス(RSV)、パピローマウィルス、パポバウィルス、サイトメガロウィルス、エキノウィルス、アルボウィルス、ハンタウィルス、コクサッキーウィルス、ムンプスウィルス、麻疹ウィルス、風疹ウィルス、ポリオウィルス、I型ヒト免疫不全ウィルス(HIV−I)、およびII型ヒト免疫不全ウィルス(HIV−II)からなる群から選択される、請求項12に記載の使用。
- 前記炎症誘発性疾患が、関節リウマチ、喘息、多発性硬化症、1型糖尿病、紅斑性狼瘡、乾癬、および炎症性大腸炎である、請求項12に記載の使用。
- 前記血管新生に関連する疾患が、糖尿病性網膜症、血管腫、子宮内膜症、および腫瘍血管新生である、請求項12に記載の使用。
- 前記線維形成性疾患が、硬化性皮膚炎、多発性筋炎、全身性紅斑性狼瘡、肝硬変、ケロイド形成、間質性腎炎、および肺線維症である、請求項12に記載の使用。
- 誤ったタンパク質の折り畳みまたは凝集が主な原因因子である前記疾患が、スクレイピー、クロイツフェルトヤコブ病、ハンチントン病、またはアルツハイマー病である、請求項12に記載の使用。
- 少なくとも1種の式Iの化合物、ならびに/あるいはそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物、ならびに少なくとも1種の追加の医薬品有効成分を含む医薬品。
- (a)有効量の式Iの化合物、ならびに/あるいはそれらの医薬品として使用可能な誘導体、塩、溶媒和物、互変異性体、および立体異性体、ならびにあらゆる比のそれらの混合物と、
(b)有効量の追加の医薬品有効成分と
の個別包装からなる一組(キット)。
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DE102005037733A DE102005037733A1 (de) | 2005-08-10 | 2005-08-10 | Adeninderivate |
DE102005037733.5 | 2005-08-10 | ||
PCT/EP2006/007147 WO2007017069A1 (de) | 2005-08-10 | 2006-07-20 | Adeninderivate |
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EP (1) | EP1912994B1 (ja) |
JP (1) | JP5033129B2 (ja) |
AR (1) | AR055604A1 (ja) |
AU (1) | AU2006278944B2 (ja) |
CA (1) | CA2618633C (ja) |
DE (1) | DE102005037733A1 (ja) |
ES (1) | ES2463683T3 (ja) |
WO (1) | WO2007017069A1 (ja) |
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AU2008281918A1 (en) * | 2007-07-27 | 2009-02-05 | F. Hoffmann-La Roche Ag | 2-azetidinemethaneamines and 2-pyrrolidinemethaneamines as TAAR-ligands |
NZ586129A (en) * | 2007-11-14 | 2012-06-29 | Myrexis Inc | Therapeutic compounds and their use in treating diseases and disorders |
DE102008027574A1 (de) | 2008-06-10 | 2009-12-17 | Merck Patent Gmbh | Neue Pyrrolidinderivate als MetAP-2 Inhibitoren |
DE102008061214A1 (de) * | 2008-12-09 | 2010-06-10 | Merck Patent Gmbh | Chinazolinamidderivate |
DE102009005193A1 (de) * | 2009-01-20 | 2010-07-22 | Merck Patent Gmbh | Neue heterocyclische Verbindungen als MetAP-2 Inhibitoren |
AR077405A1 (es) | 2009-07-10 | 2011-08-24 | Sanofi Aventis | Derivados del indol inhibidores de hsp90, composiciones que los contienen y utilizacion de los mismos para el tratamiento del cancer |
FR2949467B1 (fr) | 2009-09-03 | 2011-11-25 | Sanofi Aventis | Nouveaux derives de 5,6,7,8-tetrahydroindolizine inhibiteurs d'hsp90, compositions les contenant et utilisation |
US10940150B2 (en) | 2014-07-28 | 2021-03-09 | Technische Universitaet Dresden | Thymine derivatives and quinazoline-dione derivatives for the inhibition of HSP27 |
CN115666568A (zh) * | 2019-11-15 | 2023-01-31 | 佐治亚州立大学研究基金会 | 小分子聚合酶抑制剂 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2003037860A2 (en) * | 2001-10-30 | 2003-05-08 | Conforma Therapeutics Corporation | Purine analogs having hsp90-inhibiting activity |
US20030139427A1 (en) * | 2002-08-23 | 2003-07-24 | Osi Pharmaceuticals Inc. | Bicyclic pyrimidinyl derivatives and methods of use thereof |
JP2003528886A (ja) * | 2000-03-24 | 2003-09-30 | デューク・ユニバーシティ | Crp94−リガンド相互作用の特徴付けおよびそれに関連する精製、スクリーニングおよび治療法 |
WO2006046024A1 (en) * | 2004-10-25 | 2006-05-04 | Astex Therapeutics Limited | Ortho- condensed pyridine and pyrimidine derivatives (e. g. purines) as protein kinases inhibitors |
WO2006075095A2 (fr) * | 2005-01-13 | 2006-07-20 | Aventis Pharma S.A. | Utilisation de derives de la purine comme inhibiteurs de la proteine hsp90 et pour le traitement du cancer |
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2005
- 2005-08-10 DE DE102005037733A patent/DE102005037733A1/de not_active Withdrawn
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- 2006-07-20 EP EP06776313.6A patent/EP1912994B1/de not_active Not-in-force
- 2006-07-20 ES ES06776313.6T patent/ES2463683T3/es active Active
- 2006-07-20 AU AU2006278944A patent/AU2006278944B2/en not_active Ceased
- 2006-07-20 US US12/063,384 patent/US7977343B2/en not_active Expired - Fee Related
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- 2006-07-20 WO PCT/EP2006/007147 patent/WO2007017069A1/de active Application Filing
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JP2003528886A (ja) * | 2000-03-24 | 2003-09-30 | デューク・ユニバーシティ | Crp94−リガンド相互作用の特徴付けおよびそれに関連する精製、スクリーニングおよび治療法 |
WO2003037860A2 (en) * | 2001-10-30 | 2003-05-08 | Conforma Therapeutics Corporation | Purine analogs having hsp90-inhibiting activity |
US20030139427A1 (en) * | 2002-08-23 | 2003-07-24 | Osi Pharmaceuticals Inc. | Bicyclic pyrimidinyl derivatives and methods of use thereof |
WO2006046024A1 (en) * | 2004-10-25 | 2006-05-04 | Astex Therapeutics Limited | Ortho- condensed pyridine and pyrimidine derivatives (e. g. purines) as protein kinases inhibitors |
WO2006075095A2 (fr) * | 2005-01-13 | 2006-07-20 | Aventis Pharma S.A. | Utilisation de derives de la purine comme inhibiteurs de la proteine hsp90 et pour le traitement du cancer |
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US20100160352A1 (en) | 2010-06-24 |
AR055604A1 (es) | 2007-08-29 |
AU2006278944B2 (en) | 2011-11-24 |
CA2618633C (en) | 2014-02-04 |
EP1912994B1 (de) | 2014-03-12 |
AU2006278944A1 (en) | 2007-02-15 |
US7977343B2 (en) | 2011-07-12 |
EP1912994A1 (de) | 2008-04-23 |
WO2007017069A1 (de) | 2007-02-15 |
ES2463683T3 (es) | 2014-05-28 |
DE102005037733A1 (de) | 2007-02-15 |
CA2618633A1 (en) | 2007-02-15 |
JP5033129B2 (ja) | 2012-09-26 |
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