JP6804524B2 - Irak4モジュレーターとしての二環式縮合ヘテロアリールまたはアリール化合物 - Google Patents
Irak4モジュレーターとしての二環式縮合ヘテロアリールまたはアリール化合物 Download PDFInfo
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- JP6804524B2 JP6804524B2 JP2018510516A JP2018510516A JP6804524B2 JP 6804524 B2 JP6804524 B2 JP 6804524B2 JP 2018510516 A JP2018510516 A JP 2018510516A JP 2018510516 A JP2018510516 A JP 2018510516A JP 6804524 B2 JP6804524 B2 JP 6804524B2
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- Prior art keywords
- methoxy
- carboxamide
- alkyl
- mmol
- oxopyrrolidine
- Prior art date
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- 125000001072 heteroaryl group Chemical group 0.000 title claims description 34
- 125000002619 bicyclic group Chemical group 0.000 title description 3
- 101000977771 Homo sapiens Interleukin-1 receptor-associated kinase 4 Proteins 0.000 title 1
- 102100023533 Interleukin-1 receptor-associated kinase 4 Human genes 0.000 title 1
- 150000001875 compounds Chemical group 0.000 claims description 335
- 239000000203 mixture Substances 0.000 claims description 203
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 96
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 79
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 150000003839 salts Chemical class 0.000 claims description 57
- 239000001257 hydrogen Substances 0.000 claims description 53
- 229910052736 halogen Inorganic materials 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 45
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- 125000003118 aryl group Chemical group 0.000 claims description 40
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 38
- 208000035475 disorder Diseases 0.000 claims description 33
- 229910052805 deuterium Inorganic materials 0.000 claims description 31
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 29
- 125000005842 heteroatom Chemical group 0.000 claims description 27
- 150000002431 hydrogen Chemical class 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
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Classifications
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Description
X、X’、Y、およびY’は、それぞれ独立に、CHまたはNであり、Zは、CまたはNであり、但し、X、X’、Z、Y、およびY’のうちの3個以下は、Nであり、
R1は、C1〜C6アルキルまたは−(C1〜C6アルキル)n(C1〜C6シクロアルキル)であり、アルキルまたはシクロアルキルは、重水素、ハロゲン、CN、OH、またはC1〜C6アルコキシで置換されていてもよく、
R2は、水素またはメチルであり、
R3は、水素、重水素、ハロゲン、ニトリル、−(CH2)tNR8aR8b、−(CH2)t(6〜10員アリール)、またはN、O、もしくはSから選択される1〜3個のヘテロ原子を有する−(CH2)t(5〜10員ヘテロアリール)であり、前記アリールまたはヘテロアリールは、1〜3個のC1〜C6アルキル、重水素、ハロゲン、CN、OH、ヒドロキシC1〜C6アルキル、またはC1〜C6アルコキシで置換されていてもよく、アルキルは、ヒドロキシル、ハロゲン、CN、またはC1〜C3アルコキシで置換されていてもよく、
R4aおよびR4bは、それぞれ独立に、水素、フッ素、OH、C1〜C3アルコキシ、またはCH2OR7であり、R7は、R1と一緒になり、ハロゲンまたはアルキルで置換されていてもよいC1〜C4アルキレンであり、
R5aおよびR5bは、それぞれ独立に、水素、C1〜C3アルキル、もしくはC1〜C3−アルコキシであり、前記アルキルもしくはアルコキシは、1〜3個の重水素、ハロゲン、OH、もしくはCNで置換されていてもよく、またはR5aおよびR5bは、それらが結合している原子と一緒になり、C3〜C7シクロアルキルもしくはC3〜C7ヘテロシクロアルキルを形成し、前記シクロアルキルもしくはヘテロシクロアルキルは、1〜3個の重水素、ハロゲン、OH、CN、もしくはC1〜C3アルキルで置換されていてもよく、
R6は、水素もしくはC1〜C3アルキルであり、またはR5bおよびR6は、それらが結合している原子と一緒になり、C3〜C7シクロアルキルもしくはC3〜C7ヘテロシクロアルキルを形成し、前記シクロアルキルもしくはヘテロシクロアルキルは、1〜3個の重水素、ハロゲン、OH、CN、もしくはC1〜C3アルキルで置換されていてもよく、
R8aおよびR8bは、それぞれ独立に、水素、−S(O)2R9、または−C(O)R9であり、
R9は、C1〜C6アルキル、C1〜C6シクロアルキル、6〜10員アリール、または1〜3個のヘテロ原子を有する5〜10員ヘテロアリールであり、前記アルキル、シクロアルキル、アリール、またはヘテロアリールは、1〜3個のC1〜C6アルキル、ハロゲン、CN、OH、C1〜C6アルコキシ、またはC1〜C6ヒドロキシで置換されていてもよく、
nは、0または1であり、
tは、0、1、2、または3である)の化合物、または前記化合物の薬学的に許容できる塩または前記化合物もしくは前記塩の互変異性体を提供する。
本明細書において別段の定義がない限り、本発明に関して使用される科学技術用語は、当業者により一般に理解される意味を有する。本明細書および添付の特許請求の範囲で使用する場合、単数形「1つの(a)」、「1つの(an)」、および「その(the)」は、文脈上そうでないことが明白に要求されない限り、複数の対象物を含む。
一実施形態では、上記におよび本明細書により完全に記載するように、本発明は、式I
X、X’、Y、およびY’は、それぞれ独立に、CHまたはNであり、Zは、CまたはNであり、但し、X、X’、Z、Y、およびY’のうちの3個以下は、Nであり、
R1は、C1〜C6アルキルまたは−(C1〜C6アルキル)n(C1〜C6シクロアルキル)であり、アルキルまたはシクロアルキルは、重水素、ハロゲン、CN、OH、またはC1〜C6アルコキシで置換されていてもよく、
R2は、水素またはメチルであり、
R3は、水素、重水素、ハロゲン、ニトリル、−(CH2)tNR8aR8b、−(CH2)t(6〜10員アリール)、またはN、O、もしくはSから選択される1〜3個のヘテロ原子を有する−(CH2)t(5〜10員ヘテロアリール)であり、前記アリールまたはヘテロアリールは、1〜3個のC1〜C6アルキル、重水素、ハロゲン、CN、OH、ヒドロキシC1〜C6アルキル、またはC1〜C6アルコキシで置換されていてもよく、アルキルは、ヒドロキシル、ハロゲン、CN、またはC1〜C3アルコキシで置換されていてもよく、
R4aおよびR4bは、それぞれ独立に、水素、フッ素、OH、C1〜C3アルコキシ、またはCH2OR7であり、R7は、R1と一緒になり、ハロゲンまたはアルキルで置換されていてもよいC1〜C4アルキレンであり、
R5aおよびR5bは、それぞれ独立に、水素、C1〜C3アルキル、もしくはC1〜C3−アルコキシであり、前記アルキルもしくはアルコキシは、1〜3個の重水素、ハロゲン、OH、もしくはCNで置換されていてもよく、またはR5aおよびR5bは、それらが結合している原子と一緒になり、C3〜C7シクロアルキルもしくはC3〜C7ヘテロシクロアルキルを形成し、前記シクロアルキルもしくはヘテロシクロアルキルは、1〜3個の重水素、ハロゲン、OH、CN、もしくはC1〜C3アルキルで置換されていてもよく、
R6は、水素もしくはC1〜C3アルキルであり、またはR5bおよびR6は、それらが結合している原子と一緒になり、C3〜C7シクロアルキルもしくはC3〜C7ヘテロシクロアルキルを形成し、前記シクロアルキルもしくはヘテロシクロアルキルは、1〜3個の重水素、ハロゲン、OH、CN、もしくはC1〜C3アルキルで置換されていてもよく、
R8aおよびR8bは、それぞれ独立に、水素、−S(O)2R9、または−C(O)R9であり、
R9は、C1〜C6アルキル、C1〜C6シクロアルキル、6〜10員アリール、または1〜3個のヘテロ原子を有する5〜10員ヘテロアリールであり、前記アルキル、シクロアルキル、アリール、またはヘテロアリールは、1〜3個のC1〜C6アルキル、ハロゲン、CN、OH、C1〜C6アルコキシ、またはC1〜C6ヒドロキシで置換されていてもよく、
nは、0または1であり、
tは、0、1、2、または3である)の化合物、または前記化合物の薬学的に許容できる塩または前記化合物もしくは前記塩の互変異性体を対象とする。
R1は、C1〜C6アルキルまたは−(C1〜C6アルキル)n(C1〜C6シクロアルキル)であり、アルキルまたはシクロアルキルは、重水素、ハロゲン、CN、OH、またはC1〜C6アルコキシで置換されていてもよく、
R2は、水素であり、
R3は、水素、重水素、ハロゲン、ニトリル、−(CH2)tNR8aR8b、−(CH2)t(6〜10員アリール)、またはN、O、もしくはSから選択される1〜3個のヘテロ原子を有する−(CH2)t(5〜10員ヘテロアリール)であり、前記アリールまたはヘテロアリールは、1〜3個のC1〜C6アルキル、重水素、ハロゲン、CN、OH、ヒドロキシC1〜C6アルキル、またはC1〜C6アルコキシで置換されていてもよく、
R4aおよびR4bは、それぞれ独立に、水素、フッ素、OH、C1〜C3アルコキシ、またはCH2OR7であり、R7は、R1と一緒になり、ハロゲンまたはアルキルで置換されていてもよいC1〜C4アルキレンであり、
R5aおよびR5bは、独立に、水素、C1〜C3アルキル、もしくはC1〜C3−アルコキシであり、前記アルキルもしくはアルコキシは、1〜3個の重水素、ハロゲン、OH、もしくはCNで置換されていてもよく、またはR5aおよびR5bは、それらが結合している原子と一緒になり、C3〜C7シクロアルキルもしくはC3〜C7ヘテロシクロアルキルを形成し、前記シクロアルキルもしくはヘテロシクロアルキルは、1〜3個の重水素、ハロゲン、OH、CN、もしくはC1〜C3アルキルで置換されていてもよく、
R6は、水素もしくはC1〜C3アルキルであり、またはR5bおよびR6は、それらが結合している原子と一緒になり、C3〜C7シクロアルキルもしくはC3〜C7ヘテロシクロアルキルを形成し、前記シクロアルキルもしくはヘテロシクロアルキルは、1〜3個の重水素、ハロゲン、OH、CN、もしくはC1〜C3アルキルで置換されていてもよく、
R8aおよびR8bは、それぞれ独立に、水素、−S(O)2R9、または−C(O)R9であり、
R9は、C1〜C6アルキル、C1〜C6シクロアルキル、6〜10員アリール、または1〜3個のヘテロ原子を有する5〜10員ヘテロアリールであり、前記アルキル、シクロアルキル、アリール、またはヘテロアリールは、1〜3個のC1〜C6アルキル、ハロゲン、CN、OH、C1〜C6アルコキシ、またはC1〜C6ヒドロキシで置換されていてもよく、
nは、0または1であり、tは、0、1、2、または3である)の化合物を対象とする。
R6は、水素であり、R8aおよびR8bは、それぞれ独立に、水素、−S(O)2R9、または−C(O)R9であり、R9は、C1〜C6アルキル、C1〜C6シクロアルキル、6〜10員アリール、または1〜3個のヘテロ原子を有する5〜10員ヘテロアリールであり、前記アルキル、シクロアルキル、アリール、またはヘテロアリールは、1〜3個のC1〜C6アルキル、ハロゲン、CN、OH、C1〜C6アルコキシ、またはC1〜C6ヒドロキシで置換されていてもよく、tは、0または1である。
本発明の化合物はまた、IRAK酵素が介在する、またはそうでなければIRAK酵素に関連する疾患もしくは状態の治療および/または予防に有用であり、その方法は、有効量の本発明の化合物を、それを必要とする対象に投与するステップを含む。
非ステロイド系抗炎症薬NSAID)、限定するものではないが、これには、非選択性COX1/2阻害剤、例えば、ピロキシカム、ナプロキセン、フルビプロフェン(flubiprofen)、フェノプロフェン、ケトプロフェン、イブプロフェン、エトドラク(ロジン)、メファナム酸(mefanamic acid)、スリンダク、アパゾン、ピラゾロン(フェニルブタゾンなど)、サリチル酸塩(アスピリンなど)など;選択的COX2阻害剤、例えば、セレコキシブ、ロフェコキシブ、エトリコキシブ、バルデコキシブ、メロキシカムなどがある;
免疫調節および/または抗炎症剤、限定するものではないが、メトトレキセート、レフルノミド、シクレソニド、クロロキン、ヒドロキシクロロキン、d−ペニシラミン、オーラノフィン、スルファサラジン、アウロチオマレイン酸ナトリウム、シクロスポリン、アザチオプリン、クロモリン、ヒドロキシカルバミド、レチノイド、フマル酸塩(フマル酸モノメチルやフマル酸ジメチルなど)、酢酸グラチラマー、ミトキサントロン、テリフルノミド、トシル酸スプラタスト、ミコフェノール酸モフェチルおよびシクロホスファミド、ラキニモド、ボクロスポリン、PUR−118、AMG 357、AMG 811、BCT197がある;
抗マラリア剤、限定するものではないが、これには、ヒドロキシクロロキン(プラケニル)およびクロロキン(アラレン)、シクロホスファミド(シトキサン)、メトトレキセート(リウマトレックス)、アザチオプリン(イムラン)、メサラミン(アサコール)およびスルファサラジン(アザルフィジン)がある:
抗生剤、限定するものではないが、これには、フラジールまたはシプロフロキサシンがある;
抗TNFα剤、限定するものではないが、これには、インフリキシマブ、アダリムマブ、セルトリズマブペゴール、ゴリムマブ、およびエタネルセプトがある;
抗CD20剤、限定するものではないが、これには、リツキシマブ、オクレリズマブ、オファツムマブ、およびPF−05280586がある;
止痢薬、例えば、ジフェノキシレート(ロモティル)およびロペラミド(イモジウム)など;
胆汁酸結合剤、例えば、コレスチラミン、アロセトロン(ロトロネックス)、およびウビプロストン(ubiprostone)(アミティーザ)など;
緩下剤、例えば、マグネシアミルク剤、ポリエチレングリコール(ミララックス)、ドゥルコラックス、コレクトールおよびセノコット、ならびにジサイクロミン(ベンチル)などの抗コリン作用剤または鎮痙剤など;
Tリンパ球活性化阻害剤、限定するものではないが、これには、アバタセプトがある:
抗IL1治療剤、限定するものではないが、これには、アナキンラ、リロナセプト、カナキヌマブ、ゲボキズマブ、MABp1、およびMEDI−8968がある;
経口的に、吸入により、注射により、局所的に、直腸に、眼送達により投与することができるグルココルチコイド受容体モジュレーター、限定するものではないが、これには、ベタメタゾン、プレドニゾン、ヒドロコルチゾン、プレドニゾロン、フルニソリド、トリアムシノリンアセトニド(triamcinoline)、ベクロメタゾン、ジプロピオネート、ブデソニド、プロピオン酸フルチカゾン、シクレソニド、フロ酸モメタゾン、フルオシノニド、デスオキシメタゾン、メチルプレドニゾロン、またはPF−04171327がある;
アミノサリチル酸誘導体、限定するものではないが、これには、スルファサラジンおよびメサラジンがある;
抗α4インテグリン剤、限定するものではないが、これには、ナタリズマブがある;
α1−またはα2−アドレナリン作動性アゴニスト剤、限定するものではないが、これには、プロピルヘキシドリン(propylhexidrine)、フェニレフリン、フェニルプロパノールアミン、プソイドエフェドリンまたは塩酸ナファゾリン、塩酸オキシメタゾリン、塩酸テトラヒドロゾリン、塩酸キシロメタゾリンまたは塩酸エチルノルエピネフリンがある;
β−アドレナリン作動性アゴニスト、限定するものではないが、これには、メタプロテレノール、イソプロテネロール、イソプレナリン、アルブテロール、サルブタモール、ホルモテロール、サルメテロール、テルブタリン、オルシプレナリン、メシル酸ボトルテロール、ピルブテロールがある;
抗コリン作動剤、限定するものではないが、これには、臭化イプラトロピウム、臭化チオトロピウム、臭化オキシトロピウム、臭化アクリジニウム(aclindinium bromide)、グリコピロレート、ピレンジピン(pirenzipine)、またはテレンゼピンがある;
吸入型長時間作用性ベータ−アゴニスト、長時間作用性ムスカリンアンタゴニスト、および長時間作用性コルチコステロイド、限定するものではないが、これには、以下の参考文献に含まれるものがある:Y.Mushtaq、The COPD pipeline、Nat Rev Drug Discov、2014、13(4)、253〜254。http://dx.doi.org/10.1038/nrd425;
ロイコトリエン経路モジュレーター、限定するものではないが、これには、5−LO阻害剤(ジロートンなど)、FLAPアンタゴニスト(ベリフラポン、フィボフラポンなど)、LTD4アンタゴニスト(モンテルカスト、ザフィルルカスト、またはプランルカストなど)がある;
H1受容体アンタゴニスト、限定するものではないが、これには、セチリジン、ロラチジン、デスロラチジン、フェキソフェナジン、アステミゾール、アゼラスチン、またはクロルフェニラミンがある;
PDE4阻害剤、限定するものではないが、これには、アプレミラスト、ロフルミラスト、またはAN2728がある;
ビタミンD受容体モジュレーター、限定するものではないが、これには、パリカルシトールがある;
Nrf2経路活性化剤、限定するものではないが、これには、フマル酸塩、スルフォロファン、およびバルドキソロンメチルがある;
RAR関連オーファン受容体(ROR)ファミリーのモジュレーター、特に、RORg;
ケモカイン受容体のモジュレーターおよび/またはアンタゴニスト、限定するものではないが、これには、CCR2アンタゴニスト(CCX140、BMS−741672、PF−4634817、CCX−872、NOX−E36など)、CCR2/5アンタゴニスト(PF−4634817など)、CCR9(ベルシルノン、CCX507など)、CCR1モジュレーター、CCR4モジュレーター、CCR5モジュレーター、CCR6モジュレーター、CXCR6モジュレーター、CXCR7モジュレーター)、およびCXCR2モジュレーター(ダニリキシン、AZD5069など)がある;
プロスタグランジン、限定するものではないが、これには、プロスタシクリンがある;
PDE5阻害剤、限定するものではないが、これには、シルデナフィル、PF−489791、バルデナフィル、およびタダラフィルがある;
エンドセリン受容体アンタゴニスト、限定するものではないが、これには、ボセンタン、アンブリセンタン、スパルセンタン、アトラセンタン、ジボテンタン、およびマシテンタンがある;
可溶性グアニル酸シクラーゼ活性化剤、限定するものではないが、これには、リオシグアトがある;
インターフェロン、限定するものではないが、これには、インターフェロンベータ−1a、インターフェロンベータ−1bがある;
スフィンゴシン−1−リン酸受容体モジュレーター、限定するものではないが、これには、フィンゴリモドおよびポネシモドがある。
補体経路の阻害剤、限定するものではないが、これには、C5aRアンタゴニスト(CCX168、PMX−53、NN8210など)、C5阻害剤(エクリズマブなど)、補体因子BおよびDの阻害剤、MASP2の阻害剤(OMS−721など)、ならびにARC−1905がある;
ヤヌスキナーゼ(JAK1、JAK2、JAK3、TYK2の複数のうちの1種)の阻害剤、限定するものではないが、これには、デセルノチニブ、セルドゥラチニブ、JTE−052、ルキソリチニブ、トファシチニブ(tofacitnib)、バリシチニブ、ペフィシチニブ、GLPG−0634、INCB−47986、INCB−039110、PF−04965842、XL−019、ABT−494、R−348、GSK−2586184、AC−410、BMS−911543、およびPF−06263276がある;
他の抗炎症または免疫調節キナーゼの阻害剤、限定するものではないが、これには、脾臓チロシンキナーゼ(SYK)阻害剤、p38 MAPキナーゼ阻害剤(PF−3715455、PH−797804、AZD−7624、AKP−001、UR−13870、FX−005、セマピモド、ペクスメチニブ、ARRY−797、RV−568、ディルマピモド、ラリメチニブなど)、PI3K阻害剤(GSK−2126458、ピララリシブ、GSK−2269557など)、PI3Kgおよび/またはPI3Kd阻害剤(CAL−101/GS−1101、ドゥベリシブなど)、JNK阻害剤、ERK1および/または2阻害剤、IKKb阻害剤、BTK阻害剤、ITK阻害剤、ASK1阻害剤(GS−4997など)、PKC阻害剤(ソトラスタウリンなど)、TrkAアンタゴニスト(CT−327など)、MEK1阻害剤(E6201など)がある;
抗酸化剤、限定するものではないが、これには、ミエロペルオキシダーゼ阻害剤(AZD−3241など)、NOX4および他のNOX酵素(GKT−137831など)、ならびにN−アセチルシステインがある;
IL5の阻害剤、限定するものではないが、これには、メポリズマブ、レスリズマブ、およびベンラリズマブがある;
IL4の阻害剤、限定するものではないが、これには、パソコリズマブ、アルトラキンセプト、およびピトラキンラがある;
IL13の阻害剤、限定するものではないが、これには、トラロキヌマブ、アンルキンズマブ、およびレブリキズマブがある;
抗IL6剤、限定するものではないが、これには、トシリズマブ、オロキズマブ、シルツキシマブ、PF−4236921、およびシルクマブがある;
IL17/IL17Rの阻害剤/アンタゴニスト、限定するものではないが、これには、セクキヌマブ、RG−7624、ブロダルマブ、およびイクセキズマブがある;
IL12および/またはIL23のアンタゴニスト、限定するものではないが、これには、チルドラキズマブ、グセルクマブ、MEDI2070、およびAMG 139がある;
IL33の阻害剤、限定するものではないが、これには、AMG 282がある;
IL9の阻害剤、限定するものではないが、これには、MEDI−528がある;
GM−CSFの阻害剤、限定するものではないが、これには、MT203がある;
抗CD4薬剤、限定するものではないが、これには、トレガリズマブおよびリゲリモドがある;
CRTH2アンタゴニスト、限定するものではないが、これには、AZD−1981がある;
Bリンパ球刺激物質(BLYS;BAFFとしても公知)、SLE患者においてしばしば増加するタンパク質の阻害剤、限定するものではないが、これには、ベリムマブ、タバルマブ、ブリシビモド、およびアタシセプトがある;
CD22特異的モノクローナル抗体、限定するものではないが、これには、エプラツズマブがある;
インターフェロン−αの阻害剤、限定するものではないが、これには、シファリムマブおよびロンタリズマブがある;
I型インターフェロン受容体の阻害剤、限定するものではないが、これには、MEDI−546がある;
FcγRIIBアゴニスト、限定するものではないが、これには、SM−101がある;
熱ショックタンパク質10(Hsp10、シャペロニン10またはEPFとしても公知)の変性および/または組換え版、限定するものではないが、これには、INV−103がある;
TNFスーパーファミリー受容体12A(TWEAK受容体)の阻害剤、限定するものではないが、これには、BIIB−023、エナバツズマブ、およびRG−7212がある;
キサンチンオキシダーゼの阻害剤、限定するものではないが、これには、アロプリノール、ベンズブロマロン、フェブキソスタット、トピロキソスタット、チソプリン、およびイノシトールがある;
URAT1(SLC22A12としても公知)の阻害剤、限定するものではないが、これには、レシヌラド、RDEA 3170、UR1102、およびレボトフィスパム(levotofispam)がある;
痛風の追加治療および/または尿酸レベルの低減、限定するものではないが、これには、コルヒチン、ペグロチカーゼ、ベンズヨーダロン、イソブロミニジオン、BCX4208、およびアルハロフェナートがある;
Toll様受容体(TLR)の阻害剤、限定するものではないが、これには、TLR7、TLR8、TLR9(IMO−8400、IMO−3100、DV−1179など)、TLR2、および/またはTLR 4(VB−201、OPN−305など)のうちの1種または複数種がある;
TLRのアゴニスト、限定するものではないが、これには、TLR7(GSK2245035、AZD8848など)、TLR9(AZD1419など)がある;
活性化剤SIRT1、限定するものではないが、これには、SRT2104がある;
A3受容体アゴニスト、限定するものではないが、これには、CF101がある;
乾癬の治療に役立つ他の薬剤、限定するものではないが、これには、IDP−118、LAS41004、LEO 80185、LEO 90100、PH−10、WBI−1001、CNT01959、BT−061、シムジア、ウステキヌマブ、MK−3222/SCH 900222、ACT−128800、AEB071、アリトレチノイン、ASP015K、Apo805K1、BMS−582949、FP187、ヘクトラール(ドキセルパルシフェロール)、LEO 22811、Ly3009104(INCB28050)、カルシポトリエンフォーム(STF 115469)、トファシチニブ(CP−690、550)、M518101、およびCycloPsorb(商標)がある;
抗線維化剤、限定するものではないが、これには、ピルフェニドン、LOXL2の阻害剤(シムツズマブなど)、FT−011、エピレグリンおよび/またはTGFαのモジュレーター(LY−3016859など)、TGFβのモジュレーター(LY−2382770、フレソリムマブなど)がある;
プロリルヒドロキシラーゼ阻害剤、限定するものではないが、これには、GSK1278863、FG−2216、ASP−1517/FG−4592、AKB−6548、JTZ−951、BAY−85−3934、およびDS−1093がある;
顆粒球マクロファージコロニー刺激因子の阻害剤、限定するものではないが、これには、GSK3196165(MOR103)、PD−0360324、およびマブリリムマブがある;
MAdCAMおよび/またはα4β7インテグリンの阻害剤、限定するものではないが、これには、PF−00547659およびMEDI7183(アブリルマブ)がある;
結合組織増殖因子(CTGF)の阻害剤、限定するものではないが、これには、PF−06473871がある;カテプシンCの阻害剤、限定するものではないが、これには、GSK2793660がある;
可溶性エポキシド加水分解酵素の阻害剤、限定するものではないが、これには、GSK2269557がある;
TNFR1関連死ドメインタンパク質の阻害剤、限定するものではないが、これには、GSK2862277がある;
抗CD19剤、限定するものではないが、これには、MEDI−551およびAMG 729がある;
ICOSリガンドの抗B7RP1剤/阻害剤、限定するものではないが、これには、MEDI5872およびAMG−557がある;
胸腺間質性リンパタンパク質の阻害剤、限定するものではないが、これには、AMG157がある;
IL2の阻害剤、限定するものではないが、これには、ダクリズマブがある;
ロイシンリッチリピート神経タンパク質6Aの阻害剤、限定するものではないが、これには、抗リンゴ(バイオゲン)がある;
インテグリンの阻害剤、限定するものではないが、これには、アルファ−V/ベータ−6(STX−100)およびアルファ−V/ベータ−3(VPI−2690B)がある;
抗CD40L剤、限定するものではないが、これには、CDP−7657がある;
ドーパミンD3受容体のモジュレーター、限定するものではないが、これには、ABT−614がある;
ガレクチン−3の阻害剤および/またはモジュレーター、限定するものではないが、これには、GCS−100およびGR−MD−02がある;
糖尿病性腎症を治療するための薬剤、限定するものではないが、これには、DA−9801およびASP−8232がある;
急性腎損傷を治療するための薬剤、限定するものではないが、これには、THR−184、TRC−160334、NX−001、EA−230、ABT−719、CMX−2043、BB−3、およびMTP−131がある;
インフラマソームのモジュレーター、限定するものではないが、これには、NLRP3の阻害剤がある;
ブロモドメインのモジュレーター、限定するものではないが、これには、BRD4がある;
GPR43のモジュレーター;ならびに
TRPチャネルの阻害剤、限定するものではないが、これには、TRPA1、TRPC3、TRPC5、TRPC6、およびTRPC6がある。
式Iaの化合物は、以下に記載の方法、ならびに有機化学の分野で公知の合成方法、または当業者によく知られている修飾および変換によって調製することができる。本明細書で使用する出発材料は、市販されているか、または当技術分野で公知の常法[例えば、Compendium of Organic Synthetic Methods、Vol.I〜XII(Wiley−Interscience刊)などの標準の参考書に開示の方法]によって調製することができる。好ましい方法として、以下に記載の方法が挙げられるが、これらだけに限らない。
本発明の様々な化合物の合成を以下で説明する。本発明の範囲内の追加の化合物は、これらの実施例において説明する方法を単独でまたは当技術分野で通常公知の技術と組み合わせて使用して、調製することができる。
実験は、通常、特に酸素または水分に敏感な試薬または中間体が用いられる場合、不活性雰囲気(窒素またはアルゴン)下で行った。適切な場合には無水溶媒(通常、Aldrich Chemical Company、Milwaukee、WisconsinのSure−Seal(商標)製品)を含めた市販の溶媒および試薬をさらに精製することなく通常使用した。生成物は、真空下で通常乾燥させた後、さらなる反応を行うか、または生物学的試験にかけた。質量分析データは、液体クロマトグラフィー−質量分析(LCMS)、大気圧化学電離(APCI)、またはガスクロマトグラフィー−質量分析(GCMS)装置により報告される。核磁気共鳴(NMR)データの化学シフトは、用いた重水素化溶媒の残存ピークを参照し、百万分率(ppm、δ)で表す。
略語
ACE−Cl:クロロギ酸1−クロロエチル
Boc:tert−ブトキシカルボニル
CO:一酸化炭素
DBU:1,8−ジアザビシクロ[5.4.0]ウンデカ−7−エン
DCE:ジクロロエタン
DCM:ジクロロメタン
DIEA:ジイソプロピルエチルアミン
DMAP:4−ジメチルアミノピリジン
DMF:ジメチルホルムアミド
DMSO:ジメチルスルホキシド
EDCI:1−エチル−3−(3−ジメチルアミノプロピル)カルボジイミド
EtOAc:酢酸エチル
EtOH:エチルアルコール
FA:ギ酸
h:時間
HATU:O−(7−アザベンゾトリアゾール−1−イル)−N,N,N’,N’−テトラメチルウロニウムヘキサフルオロホスフェート
HCl:塩酸
HNO3:硝酸
H2O:水
H2O2:過酸化水素
HOAc:酢酸
HOBT:ヒドロキシベンゾトリアゾール
H2SO4:硫酸
K2CO3:炭酸カリウム
KHMDS:カリウムビス(トリメチルシリル)アミド
LiOH・H2O:水酸化リチウム一水和物
PMB:パラ−メトキシベンジル
MeCN:アセトニトリル
MeOH:メタノール
MgSO4:硫酸マグネシウム
min:分
MS:質量分析
Na:ナトリウム
Na2S2O3:ヒドロ亜硫酸ナトリウム
Na2SO4:硫酸ナトリウム
NH4Cl:塩化アンモニウム
NaHCO3:重炭酸ナトリウム
NaHMDS:ナトリウムビス(トリメチルシリル)アミド
N−BuLi:n−ブチルリチウム
NBS:N−ブロモスクシンイミド
Pd(PPh3)4:テトラキス(トリフェニルホスフィン)パラジウム(0)
PdCl2(dppf):[1,1’−ビス(ジフェニルホスフィノ)フェロセン]ジクロロパラジウム(II)、
POCl3:オキシ塩化リン
SNAr:芳香族求核置換
TBAF:テトラブチルアンモニウムフルオリド
TBA−HSO4:硫酸水素テトラブチルアンモニウム
TBS:tert−ブチルシリル
TBSCl:tert−ブチルジメチルシリルクロリド
TEA:トリエチルアミン
TFA:トリフルオロ酢酸
TFAA:無水トリフルオロ酢酸
THF:テトラヒドロフラン
TLC:薄層クロマトグラフィー
Zn:亜鉛
8−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−2−メトキシキノリン−3−カルボキサミド
(m, 1H), 7.36-7.43 (m, 1H), 7.30-7.35 (m, 1H).HPLC:Ultimate XB−C18、3um、3.0×50mm、SN:111201514、移動相:1分間で水中1%MeCN(0.1%TFA)〜水中5%MeCN(0.1%TFA)にし、次いで5分間で水中5%MeCN(0.1%TFA)〜100%MeCN(0.1%TFA)にし、2分間100%MeCN(0.1%TFA)に保持し、次いで8.01分の時点で水中1%MeCN(0.1%TFA)に戻し、2分間保持する。流速1.2ml/分。保持時間3.19分。
ステップ2:ジメチル2−(3−ヒドロキシ−2−ニトロベンジリデン)マロネートの調製
7.22 (d, 1H), 6.86 (d, 1H), 3.90 (s, 3H), 3.62 (s, 3H).HPLC:Ultimate XB−C18、3um、3.0×50mm、SN:111201514、移動相:1分間で水中1.0%MeCN(0.1%TFA)〜水中5%MeCN(0.1%TFA)にし、次いで5分間で水中5%MeCN(0.1%TFA)〜100%MeCN(0.1%TFA)にし、2分間100%MeCN(0.1%TFA)に保持し、次いで8.01分の時点で水中1%MeCN(0.1%TFA)に戻し、2分間保持する。流速1.2ml/分。保持時間3.92分。
ステップ3:メチル8−ヒドロキシ−2−オキソ−1,2−ジヒドロキノリン−3−カルボキシレートの調製
7.26 (d, 1H), 7.06-7.16 (m, 2H), 3.90 (s, 3H). MS m/z 220 [M+H]+.
ステップ4:メチル8−(ベンジルオキシ)−2−オキソ−1,2−ジヒドロキノリン−3−カルボキシレートの調製
2H), 7.36-7.44 (m, 3H), 7.27-7.36 (m, 2H), 7.14 (t, 1H), 5.32 (s, 2H), 3.82 (s,
3H). MS m/z 310 [M+H]+.
ステップ5:メチル8−ヒドロキシ−2−メトキシキノリン−3−カルボキシレートの調製
7.37-7.46 (m, 3H), 7.29-7.36 (m, 3H), 7.21 (d, 1H), 5.38 (s, 2H), 4.23 (s, 3H),
4.19 (s, 2H), 3.98 (s, 4H).Waters Acquity HSS T3、2.1×50mm、C18、1.7μm;カラム温度60℃、水中0.1%ギ酸(v/v);移動相B:MeCN中0.1%ギ酸(v/v)、流速−1.25ml/分、初期条件:A−95%:B−5%;0.0〜0.1分は初期に保持;0.1〜1.0分にかけてA−5%:B−95%に直線ランプ;1.0〜1.1分はA−5%:B−95%に保持;1.1〜1.5分で初期条件に戻す。保持時間0.81分。MS m/z 234 [M+H]+.
ステップ6:8−ヒドロキシ−2−メトキシキノリン−3−カルボキサミドの調製
1H), 7.72 (br s, 1H), 7.50 (d, 1H), 7.43 (d, 1H), 7.22-7.38 (m, 6H), 7.10-7.17
(m, 1H), 5.81 (br s, 2H), 5.30 (s, 1H), 4.21 (s, 2H), 4.18 (s, 3H).Waters Acquity HSS T3、2.1×50mm、C18、1.7μm;カラム温度60℃、水中0.1%ギ酸(v/v);移動相B:MeCN中0.1%ギ酸(v/v)、流速−1.25ml/分、初期条件:A−95%:B−5%;0.0〜0.1分は初期に保持;0.1〜1.0分にかけてA−5%:B−95%に直線ランプ;1.0〜1.1分はA−5%:B−95%に保持;1.1〜1.5分で初期条件に戻す。保持時間0.74分。MS m/z 219 [M+H]+.
ステップ7:8−ヒドロキシ−2−メトキシキノリン−3−カルボニトリルの調製
7.38-7.49 (m, 4H), 7.31-7.38 (m, 3H), 5.39 (s, 1H), 4.25 (s, 2H), 4.23 (s, 3H).Waters Acquity HSS T3、2.1×50mm、C18、1.7μm;カラム温度60℃、水中0.1%ギ酸(v/v);移動相B:アセトニトリル中0.1%ギ酸(v/v)、流速−1.25ml/分、初期条件:A−95%:B−5%;0.0〜0.1分は初期に保持;0.1〜1.0分にかけてA−5%:B−95%に直線ランプ;1.0〜1.1分はA−5%:B−95%に保持;1.1〜1.5分で初期条件に戻す。保持時間0.89分。MS m/z 201 [M+H]+.
ステップ8:8−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−2−メトキシキノリン−3−カルボニトリルの調製
1H), 6.86 (br s, 1H), 4.95 (d, 0.5 H), 4.82 (d, 0.5H), 4.40 (d, 1H), 4.17-4.27
(m, 5H), 2.46-2.67 (m, 1H), 1.57-1.87 (m, 2H), 1.15 (t, 3H). MS m/z 344 [M+H]+.
ステップ9:8−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−2−メトキシキノリン−3−カルボキサミドの調製
DMSO中の8−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−2−メトキシキノリン−3−カルボニトリル(36mg、0.10mmol)の混合物に、K2CO3(72mg、0.52mmol)を添加した。30%過酸化水素(83mg、0.73mmol)を添加した。混合物を周囲温度で4.5時間撹拌した。混合物をブラインとEtOAcとの間で分配した。層を分離し、水相をEtOAcで抽出した。合わせた有機抽出物をブラインで5回洗浄し、無水Na2SO4で乾燥させ、減圧下で濃縮した。残留物を、溶離液としてDCM中0〜5%MeOHを用いるフラッシュクロマトグラフィーにより精製して、表題化合物をオフホワイトの固体(11mg、30%)として得た。1H NMR (500 MHz, CDCl3) δ 9.00 (s, 1H), 7.88 (br s, 1H), 7.54 (d,
1H), 7.36 (t, 1H), 7.22 (d, 1H), 7.08 (br s, 1H), 6.06 (br s, 1H), 4.92 (d, 0.5
H), 4.81 (d, 0.5 H), 4.37 (dd, 1H), 4.26 (s, 3H), 4.15-4.24 (m, 2H), 2.42-2.62
(m, 1H), 1.54-1.81 (m, 2H), 1.12 (t, 3H). MS m/z
362 [M+H]+.
4−(1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
1H), 7.16 (dd, 1H), 6.56 (d, 1H), 4.90 (spt, 1H), 1.37 (d, 6H). MS m/z 229 [M+H]+.
ステップ2:4−ブロモ−1−ヒドロキシ−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
7.52 (d, 1H), 4.94 (td, 1H), 1.37 (d, 6H). MS m/z 307
[M+H]+.
ステップ3:4−ブロモ−1−クロロ−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
4.91 (td, 1H), 1.54 (d, 6H). MS m/z 326 [M+H]+.
ステップ4:4−ブロモ−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
1H), 6.47 (br s, 1H), 4.76-4.94 (m, 1H), 4.63 (dd, 1H), 4.29-4.43 (m, 1H), 4.22
(br s, 1H), 2.29-2.56 (m, 3H), 1.87-2.13 (m, 1H), 1.34-1.56 (m, 6H). MS m/z 404 [M+H]+.
ステップ5:2−(トリブチルスタンナニル)−1,3−オキサゾールの調製
ステップ6:4−(1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
7.60 (s, 1H), 7.37 (s, 1H), 6.46 (br s, 1H), 4.78-4.97 (m, 1H), 4.72 (dd, 1H),
4.47 (dd, 1H), 4.25 (br s, 1H), 2.37-2.55 (m, 3H), 2.03 (t, 1H), 1.50 (d, 6H). MS m/z 393 [M+H]+.
ステップ7:4−(1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミドの調製
DMSO(4mL)中の4−(1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリル(60mg、0.15mmol)およびK2CO3(106mg、0.76mmol)の混合物を、25℃で5分間撹拌した。H2O2(121mg、1.07mmol)を添加し、混合物を25℃で2時間撹拌した。混合物をジメチルスルフィド(95mg、1.53mmol)でクエンチし、25℃で30分間撹拌した。混合物を濾過し、DCMおよびEtOAcで洗浄した。濾液を濃縮し、残留物を分取HPLC(カラム:Ultimate XB−C18、3um、3.0×50mm、保持時間:3.46分、移動相:水中1%MeCN(0.05%TFA)〜水中100%MeCN(0.05%TFA)、流速:1.2mL/分、波長:220nm)により精製して、粗生成物(30mg、純度90%)を得た。粗生成物をMeOH(1.5mL)中で2分間撹拌し、濾過して、表題化合物を白色固体(20mg、収率32%)として得た。1H NMR (400 MHz, DMSO-d6) δ 9.43 (s, 1H), 8.57 (s, 1H), 8.32 (s, 1H),
8.17 (s, 1H), 7.78 (br s, 2H), 7.75 (s, 1H), 7.53 (s, 1H), 4.96 (td, 1H), 4.56
(dd, 1H), 4.40 (dd, 1H), 4.06 (br s, 1H), 2.17-2.38 (m, 3H), 1.94 (d, 1H), 1.41
(dd, 6H). MS m/z 433 [M+Na]+.
4−(4−メチル−1H−イミダゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
MS m/z 261 [M+H]+.
ステップ2:1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)−4−(4,4,5,5−テトラメチル−1,3,2−ジオキサボロラン−2−イル)イソキノリン−6−カルボニトリルの調製
1H), 7.78 (s, 1H), 5.00 (td, 1H), 4.54 (dd, 1H), 4.32 (dd, 1H), 4.03 (br s,
1H), 2.10-2.37 (m, 3H), 1.81-1.95 (m, 1H), 1.25-1.47 (m, 18H). MS m/z 452 [M+H]+.
ステップ3:4−(4−メチル−1H−イミダゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
8.17 (s, 1H), 7.78 (s, 1H), 7.05 (s, 0.5H),6.88 (s, 0.5H), 5.02 (td, 1H), 4.53
(dd, 1H), 4.32 (dd, 1H), 4.05 (br s, 1H), 2.20-2.32 (m, 6H),1.91 (m, 1H),
1.40-1.44 (m, 6H). MS m/z 406 [M+H]+.
ステップ4:4−(4−メチル−1H−イミダゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミドの調製
DMSO(1.0mL)中の4−(4−メチル−1H−イミダゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリル(60mg、0.15mmol)の撹拌溶液を、微細粉末K2CO3(81.8mg、0.59mmol)で処理し、得られた混合物を45℃に加熱した。この溶液に、30%H2O2(0.19mL、1.93mmol)をゆっくりと滴下添加した。45分後、反応混合物をMeOHで希釈し、濾過し、MeOHで洗浄した。濾液を減圧下で蒸発させた。粗物質を分取HPLCにより精製して、表題化合物を黄色固体(8mg、収率13%)として得た。1H NMR (400 MHz, DMSO-d6) δ 12.28 (br s, 1H), 9.19-9.42 (m, 2H), 8.15
(d, 2H), 7.72 (br s, 2H), 7.68 (s, 1H), 6.81-7.03 (m, 1H), 4.93 (td, 1H), 4.51
(dd, 1H), 4.36 (dd, 1H), 4.05 (br s, 1H), 2.18-2.31 (m, 5H), 1.89-1.99 (m, 1H),
1.40 (dd, 6H). MS m/z 424 [M+H]+.
4−(1−メチル−1H−ピラゾール−3−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
ステップ2:4−(1−メチル−1H−ピラゾール−3−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミドの調製
DMSO(1.0mL)中の4−(1−メチル−1H−ピラゾール−3−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリル(90.0mg、0.22mmol)の撹拌溶液を、微細粉末K2CO3(122.66mg、0.88mmol)で処理し、混合物を45℃に加熱した。30%H2O2(0.29ml、2.88mmol)溶液を反応混合物にゆっくりと滴下添加した。45分後、反応混合物をMeOHで希釈し、濾過し、MeOHで洗浄した。濾液を減圧下で蒸発させた。粗製物を分取HPLCにより精製して、表題化合物をオフホワイトの固体(12mg、収率13%)として得た。1H NMR (400 MHz, DMSO-d6) δ 8.88 (s, 1H), 8.11 (s, 1H), 8.07 (s, 1H),
7.85 (s, 1H), 7.64-7.76 (m, 3H), 6.61 (s, 1H), 4.94 (td, 1H), 4.50 (dd, 1H),
4.36 (dd, 1H), 4.05 (br s, 1H), 3.96 (s, 3H), 2.14-2.36 (m, 3H), 1.88-1.97 (m,
1H), 1.41 (t, 6H). MS m/z 424 [M+H]+.
4−(1−メチル−1H−ピラゾール−4−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
ステップ2:4−(1−メチル−1H−ピラゾール−4−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミドの調製
DMSO(1.0ml)中の4−(1−メチル−1H−ピラゾール−4−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリル(75.0mg、0.18mmol)の撹拌溶液を、微細粉末K2CO3(102mg、0.74mmol)で処理し、45℃に加熱した。この溶液を30%H2O2(0.24ml、2.41mmol)溶液でゆっくりと滴下処理した。45分後、反応混合物をメタノールで希釈し、濾過し、メタノールで洗浄した。濾液を減圧下で蒸発させた。粗製物を分取HPLCにより精製して、表題化合物をオフホワイトの固体(14mg、収率18%)として得た。1H NMR (400 MHz, DMSO-d6) δ 8.30 (s, 1H), 8.11 (s, 1H), 8.02 (s, 1H),
7.85 (s, 1H), 7.74 (br s, 2H), 7.72 (s, 1H), 7.68 (s, 1H), 4.95 (td, 1H), 4.49
(dd, 1H), 4.34 (dd, 1H), 3.95 (s, 3H), 2.18-2.36 (m, 3H), 1.93 (d, 1H),
1.38-1.44 (m, 6H). MS m/z 424 [M+H]+.
4−(4−メチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
10H), 1.36-1.32 (m, 9H). 1.21-1.71 (m, 8H), 0.92-0.88
(m, 14H).NMRは塩化トリブチルスズの存在を示す。
ステップ2:4−(4−メチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
7.50 (s, 1H), 6.77 (br s, 1H), 4.88 (td, 1H), 4.69 (dd, 1H), 4.44 (dd, 1H),
4.24 (br s, 1H), 2.37-2.55 (m, 3H), 2.32 (s, 3H), 1.92-2.13 (m, 1H), 1.44-1.57
(m, 6H). MS m/z 429 [M+Na]+.
ステップ3:4−(4−メチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミドの調製
DMSO(4mL)中の4−(4−メチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリル(80mg、0.20mmol)およびK2CO3(136mg、0.98mmol)の混合物を、25℃で5分間撹拌した。H2O2(156mg、1.38mmol)を添加した。反応混合物を25℃で2時間撹拌した。混合物をジメチルスルフィド(122mg、1.97mmol)でクエンチし、25℃で30分間撹拌した。混合物を濾過し、DCMおよびEtOAcで洗浄した。濾過ケークをMeOH(2mL)中に懸濁させ、2時間撹拌した。混合物を濾過し、濾過ケークをMeOH/DCM(1/10、5mL)中に懸濁させ、5分間撹拌した。混合物を濾過し、濾液を濃縮して、表題化合物をオフホワイトの固体(23mg、28%)として得た。1H NMR (400 MHz, DMSO-d6) δ 9.34 (s, 1H), 8.53 (s, 1H), 8.16 (s, 1H),
8.00 (s, 1H), 7.79 (br s, 1H), 7.74 (s, 2H), 4.86-5.02 (m, 1H), 4.55 (d, 1H),
4.39 (dd, 1H), 4.06 (br s, 1H), 2.13-2.40 (m, 6H), 1.93 (br s, 1H), 1.40 (dd,
6H). MS m/z 425 [M+H]+.
4−(4,5−ジメチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
6.29 (br s, 1H), 4.85 (td, 1H), 4.72 (dd, 1H), 4.48 (dd, 1H), 4.23 (br s, 1H),
4.00 (s, 3H), 2.31-2.53 (m, 3H), 1.93-2.15 (m, 1H), 1.49 (d, 6H). MS m/z 406 [M+Na]+.
ステップ2:6−シアノ−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−4−カルボン酸の調製
7.80 (s, 1H), 4.91-5.14 (m, 1H), 4.52-4.74 (m, 1H), 4.37 (dd, 1H), 3.89-4.18
(m, 1H), 2.12-2.36 (m, 3H), 1.91 (br s, 1H), 1.41 (dd, 6H). MS m/z 370 [M+H]+.
ステップ3:6−シアノ−N−(3−オキソブタン−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−4−カルボキサミドの調製
ステップ4:4−(4,5−ジメチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
7.04 (br s, 1H), 4.87 (td, 1H), 4.75 (dd, 1H), 4.45 (dd, 1H), 4.21-4.35 (m,
1H), 2.40-2.58 (m, 3H), 2.38 (s, 3H), 2.23 (s, 3H), 1.97-2.09 (m, 1H), 1.50
(dd, 6H). MS m/z 443 [M+Na]+.
ステップ5:4−(4,5−ジメチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミドの調製
DMSO(4mL)中の4−(4,5−ジメチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリル(100mg、0.238mmol)およびK2CO3(164mg、1.19mmol)の混合物を、25℃で5分間撹拌した。H2O2(189mg、1.66mmol)を添加し、反応混合物を25℃で2時間撹拌した。混合物をジメチルスルフィド(148mg、2.38mmol)でクエンチし、25℃で30分間撹拌した。混合物を濾過し、DCMおよびEtOAcで洗浄した。濾液を濃縮し、残留物を分取HPLC(カラム:DIKMA Diamonsil(2) C18 200×20mm×5um、移動相:水中24%MeCN(0.225%FA)〜水中44%MeCN(0.225%FA)、流速:30mL/分、波長:220nm)により精製して、表題化合物を黄色固体(23mg、収率22%)として黄色固体として得た。1H NMR (400 MHz, DMSO-d6) δ 9.36 (s, 1H), 8.47 (s, 1H), 8.15 (s, 1H),
7.77 (br s, 1H), 7.72 (s, 1H), 4.90-4.97 (m, 1H), 4.54 (d, 1H), 4.38 (dd, 1H),
4.05 (br s, 1H), 2.36 (s, 3H), 2.19-2.34 (m, 3H), 2.17 (s, 3H), 1.94 (d, 1H),
1.40 (dd, 6H). 1つのNHは不明確. MS m/z 439 [M+H]+.
4−[4−(ヒドロキシメチル)−1H−イミダゾール−2−イル]−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
4.64-4.53 (m, 2H), 1.17-1.07 (m, 3H), 1.06-0.95 (m, 18H). MS m/z 382
[M+H]+.
ステップ2:tert−ブチル2−ヨード−4−({[トリ(プロパン−2−イル)シリル]オキシ}メチル)−1H−イミダゾール−1−カルボキシレートの調製
1.02-0.94 (m, 18H).
ステップ3:1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)−4−[4−({[トリ(プロパン−2−イル)シリル]オキシ}メチル)−1H−イミダゾール−2−イル]イソキノリン−6−カルボニトリルの調製
ステップ4:4−[4−(ヒドロキシメチル)−1H−イミダゾール−2−イル]−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
ステップ5:4−[4−(ヒドロキシメチル)−1H−イミダゾール−2−イル]−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミドの調製
DMSO(2mL)中の4−[4−(ヒドロキシメチル)−1H−イミダゾール−2−イル]−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリル(95mg、0.23mmol)の撹拌溶液を、微細粉末K2CO3(125mg、0.90mmol)で処理し、45℃に加熱した。30%H2O2(0.30mL、2.93mmol)溶液をゆっくりと滴下添加した。45分後、混合物をMeOHで希釈し、濾過し、MeOHで洗浄した。濾液を減圧下で蒸発させた。粗物質を分取HPLCにより精製して、表題化合物を黄色固体(7mg、収率7%)として得た。1H NMR (400 MHz, メタノール-d4) δ 8.83 (s, 1H),
8.09 (s, 1H), 7.79 (s, 1H), 7.20 (br s, 1H), 4.99 (td, 1H), 4.67 (s, 1H),
4.52-4.66 (m, 2H), 4.24 (br s, 1H), 2.37-2.60 (m, 3H), 2.06-2.18 (m, 1H), 1.50
(t, 6H). 1つのプロトンは溶媒ピークにより不明確. MS m/z 440 [M+H]+.
4−(5−メチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
6.85 (br s, 1H), 6.34 (br s, 1H), 4.84 (td, 1H), 4.68 (dd, 1H), 4.38-4.49 (m,
3H), 4.23 (br s, 1H), 2.37-2.54 (m, 3H), 2.33 (s, 3H), 1.95-2.12 (m, 1H), 1.48
(d, 6H). MS m/z 447 [M+Na]+.
ステップ2:4−(5−メチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
6.97 (s, 1H), 6.40 (br s, 1H), 4.86 (td, 1H), 4.70 (dd, 1H), 4.46 (dd, 1H),
4.25 (br s, 1H), 2.05 (d, 1H), 1.62 (s, 3H), 1.43-1.54 (m, 6H). いくつかのピークは溶媒により不明確であった. MS m/z 429 [M+Na]+.
ステップ3:4−(5−メチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミドの調製
DMSO(4mL)中の4−(5−メチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリル(60mg、0.15mmol)およびK2CO3(102mg、0.74mmol)の混合物を、25℃で5分間撹拌した。H2O2(117mg、1.03mmol)を添加し、反応混合物を25℃で2時間撹拌した。混合物をジメチルスルフィド(91.7mg、1.48mmol)でクエンチし、25℃で30分間撹拌した。混合物を濾過し、DCMおよびEtOAcで洗浄した。濾液を濃縮し、残留物を分取HPLC(カラム:DIKMA Diamonsil(2) C18 200×20mm×5um、移動相:水中20%MeCN(0.225%FA)〜水中40%MeCN(0.225%FA)、流速:30mL/分、波長:220nm)により精製して、表題化合物を黄色固体(13mg、収率21%)として得た。1H NMR (400 MHz, DMSO-d6) δ 9.44 (s, 1H), 8.50 (s, 1H), 8.15 (s, 1H),
7.77 (br s, 1H), 7.73 (s, 1H), 7.13 (s, 1H), 4.86-5.04 (m, 1H), 4.50-4.62 (m,
1H), 4.33-4.45 (m, 1H), 4.06 (br s, 1H), 2.43 (s, 3H), 2.19-2.36 (m, 3H), 1.94
(br s, 1H), 1.40 (dd, 6H). NHプロトンは不明確. MS m/z 425 [M+H]+.
1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−4−[(フェニルスルホニル)アミノ]−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
1H), 7.16 (t, 1H), 6.56 (d, 1H), 4.82-5.01 (m, 1H), 1.37 (d, 6H). MS m/z 274 [M+H]+.
ステップ2:1−クロロ−4−ニトロ−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
1H), 7.85 (s, 1H), 4.97 (td, 1H), 1.38 (d, 6H). MS
m/z 292 [M+H]+.
ステップ3:1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−4−ニトロ−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
6.51 (s, 1H), 4.91 (td, 1H), 4.56-4.78 (m, 2H), 4.01-4.21 (m, 1H), 2.60-2.78
(m, 1H), 2.51 (dd, 1H), 2.17 (dd, 1H), 1.62-1.75 (m, 2H), 1.50 (dd, 6H), 1.03
(t, 3H).
ステップ4:4−アミノ−1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボニトリルの調製
6.93 (s, 1H), 4.71 (td, 1H), 4.35-4.51 (m, 2H), 4.01-4.08 (m, 1H), 2.56-2.69
(m, 1H), 2.42-2.52 (m, 1H), 2.20 (dd, 1H), 2.05 (s, 1H), 1.44 (dd, 6H), 0.98
(t, 3H). MS m/z 369 [M+H]+.
ステップ5:4−アミノ−1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミドの調製
2H), 7.45 (s, 1H), 7.25 (s, 1H), 5.23 (s, 2H), 4.83 (td, 1H), 4.17-4.36 (m,
2H), 3.83-3.93 (m, 1H), 3.32 (s, 1H), 2.20-2.31 (m, 1H), 2.06-2.17 (m, 1H),
1.58 (td, 1H), 1.39 (t, 6H), 0.90 (t, 3H). MS m/z 387
[M+H]+.
ステップ6:1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−4−[(フェニルスルホニル)アミノ]−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミドの調製
ピリジン(2mL)中の4−アミノ−1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド(100mg、0.26mmol)の溶液に、ベンゼンスルホニルクロリド(55mg、0.31mmol)を添加した。混合物を25℃で5時間撹拌した。水(5mL)を添加し、混合物をDCMで抽出した。合わせた有機相をNa2SO4で乾燥させた。残留物を分取HPLC(カラム:Ultimate XB−C18 3um、3.0×50mm、勾配時間:11分、移動相:水中1%MeCN(0.05%TFA)〜水中100%MeCN(0.05%TFA)、流速:35mL/分、波長:220nm)により精製して、表題化合物を白色固体(78mg、収率57%)として得た。1H NMR (400 MHz, CDCl3) δ 9.30 (br s, 1H), 8.95 (br s, 1H), 8.17 (br
s, 1H), 8.00 (s, 1H), 7.69 (d, 3H), 7.28-7.35 (m, 1H), 7.28-7.39 (m, 2H),
7.18-7.24 (m, 2H), 7.09 (br s, 1H), 4.65-4.78 (m, 1H), 4.56 (d, 1H), 4.33 (d,
1H), 4.05 (d, 1H), 2.60 (d, 1H), 2.46 (dd, 1H), 2.19 (dd, 1H), 1.57 (d, 3H),
1.44 (d, 3H), 1.38 (d, 1H), 0.96 (t, 3H). MS m/z 527
[M+H]+.
1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)−4−[(ピリジン−3−イルスルホニル)アミノ]イソキノリン−6−カルボキサミド
1H), 8.26 (br s, 1H), 7.93-8.13 (m, 3H), 7.19 (br s, 1H), 7.06 (br s, 1H), 4.71
(br s, 1H), 4.59 1H), 4.33 (br s, 1H), 4.06 (d, 1H), 2.62 (br s, 1H), 2.47 (dd,
1H), 2.19 (dd, 1H), 1.61 (d, 3H), 1.56 (br s, 2H), 1.45 (d, 3H), 1.40 (br s,
1H), 0.97 (t, 3H). MS m/z 528 [M+H]+.
1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−4−[(1H−イミダゾール−4−イルスルホニル)アミノ]−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
1H), 7.84 (s, 1H), 7.73 (br s, 1H), 7.66 (br s, 1H), 7.52 (s, 1H), 7.47 (s,
2H), 4.79-4.88 (m, 1H), 4.38 (d, 2H), 3.90 (br s, 1H), 2.21-2.35 (m, 2H), 2.04-2.15
(m, 1H), 1.51-1.63 (m, 1H), 1.38 (dd, 6H), 0.90 (t, 3H). ピークは溶媒により不明確. MS m/z 539 [M+Na]+.
1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−4−{[(1−メチル−1H−イミダゾール−4−イル)スルホニル]アミノ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
1H), 7.89 (s, 1H), 7.46 (br s, 1H), 7.34 (br s, 1H), 7.25 (br s, 1H), 7.20 (br
s, 1H), 7.12 (br s, 1H), 4.76 (br s, 1H), 4.52-4.62 (m, 1H), 4.41 (d, 1H), 4.08
(br s, 1H), 3.57 (s, 3H), 2.61 (br s, 1H), 2.47 (dd, 1H), 2.20 (dd, 1H), 1.59
(d, 2H), 1.51 (d, 3H), 1.44 (d, 3H), 0.98 (t, 3H). MS
m/z 531 [M+H]+.
4−{[(1,2−ジメチル−1H−イミダゾール−4−イル)スルホニル]アミノ}−1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド
7.71 (br s, 1H), 7.62 (br s, 1H), 7.60 (s, 1H), 7.46 (s, 1H), 7.41 (s, 1H),
4.83 (td, 1H), 4.39 (d, 2H), 3.89-3.95 (m, 1H), 3.48 (s, 3H), 2.23-2.34 (m,
5H), 2.03-2.16 (m, 2H), 1.51-1.63 (m, 1H), 1.37 (dd, 6H), 0.91 (t, 3H). MS m/z 545 [M+H]+.
4−アミノ−1−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−7−メトキシイソキノリン−6−カルボキサミド
1H), 7.41 (br s, 1H), 4.80-5.01 (m, 2H), 4.51 (dd, 1H), 4.16-4.29 (m, 1H),
4.04-4.14 (m, 3H), 2.51-2.75 (m, 1H), 1.74-1.92 (m, 1H), 1.58-1.72 (m, 1H),
1.15 (t, 3H). MS m/z 389 [M+H]+.
ステップ2:1−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−7−メトキシ−4−ニトロイソキノリン−6−カルボキサミドの調製
1H), 7.63 (s, 1H), 7.56 (br s, 1H), 6.62 (br s, 1H), 5.01 (d, 1H), 4.84-4.95
(m, 1H), 4.58 (d, 1H), 4.30 (br s, 1H), 4.03 (s, 2H), 2.56-2.75 (m, 1H), 2.18
(s, 1H), 1.99-2.10 (m, 1H), 1.64-1.90 (m, 1H), 1.16 (t, 3H). MS m/z 407 [M+H]+.
ステップ3:4−アミノ−1−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−7−メトキシイソキノリン−6−カルボキサミドの調製
亜鉛(91mg、1.39mmol)、塩化アンモニウム(75mg、1.39mmol)および1−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−7−メトキシ−4−ニトロイソキノリン−6−カルボキサミド(57mg、0.14mmol)の混合物に、水(0.7mL)、テトラヒドロフラン(0.7mL)およびエタノール(0.35mL)を添加した。混合物を周囲温度で20分間撹拌した。混合物をCeliteに通して濾過し、濾液を、DCM中0〜20%メタノールを用いるシリカゲルクロマトグラフィーにより精製して、表題化合物を固体(37mg、収率71%)として得た。1H NMR (400 MHz, メタノール-d4) δ 8.54 (s, 1H),
7.81 (s, 1H), 7.40 (s, 1H), 4.96 (dd, 1H), 4.51 (dd, 1H), 4.32 (dd, 1H), 4.17 (六重線, 1H). 4.06 (s, 3H), 2.78 - 2.61 (m, 1H),
1.84 - 1.65 (m, 2H), 1.11 (t, 3H). MS m/z 377 [M+H]+.
1−(((4R,7S)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−イソプロポキシイソキノリン−6−カルボキサミド
(m, 7H).
ステップ2:エチル2−(1−(ニトロメチル)シクロプロピル)アセテートの調製
1.28 (m, 3H), 0.88 - 0.69 (m, 4H).
ステップ3:エチル2−(1−(2−ヒドロキシ−1−ニトロエチル)シクロプロピル)アセテートの調製
3.16 (br s, OH), 2.81 (d, 1H), 2.33 (m, 1H), 2.18 (d, 1H), 1.25 - 1.16 (m, 3H),
0.97 - 0.83 (m, 2H), 0.81 - 0.69 (m, 1H), 0.67 - 0.53 (m, 1H).
ステップ4:4−(ヒドロキシメチル)−5−アザスピロ[2.4]ヘプタン−6−オンの調製
3.31 (m, 2H), 3.13 - 3.00 (m, 1H), 2.39 (d, 1H), 1.88 (d, 1H), 0.86 - 0.73 (m,
1H), 0.61 - 0.41 (m, 3H). MS m/z 142.1 [M+H]+.
ステップ5:3’,3’−ジメチルジヒドロ−3’H−スピロ[シクロプロパン−1,7’−ピロロ[1,2−c]オキサゾール]−5’(6’H)−オンの調製
ステップ6:6’−フルオロ−3’,3’−ジメチルジヒドロ−3’H−スピロ[シクロプロパン−1,7’−ピロロ[1,2−c]オキサゾール]−5’(6’H)−オンの調製
0.5H), 4.38 (m, 0.5H), 4.04 (m, 0.5H), 3.86 (m, 1H), 3.50 - 3.36 (m, 1H), 1.73
(m, 3H), 1.52 (m, 3H), 1.29 - 1.10 (m, 1H), 0.99 - 0.58 (m, 3H). MS m/z 200.1
[M+H]+
ステップ7:7−フルオロ−4−(ヒドロキシメチル)−5−アザスピロ[2.4]ヘプタン−6−オンの調製
4.98 - 4.69 (m, 0.5H), 4.57 - 4.33 (m, 0.5H), 3.55 - 3.17 (m, 4H), 1.07 - 0.55
(m, 4H).
ステップ8:1−((7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−イソプロポキシイソキノリン−6−カルボニトリルの調製
残留物をシリカゲル上でのフラッシュクロマトグラフィー(50%EtOAc−ヘキサン)により精製して、第1の溶出異性体を、黄色固体としてのラセミ1−(((anti)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−イソプロポキシイソキノリン−6−カルボニトリル(300mg、収率33%)として得た。1H NMR (400 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.52 (s, 1H), 7.97 (d, 1H),
7.61 (s, 1H), 7.42 (d, 1H), 5.14 - 4.96 (d, 1H), 4.96 - 4.87 (m, 1H), 4.45 -
4.31 (m, 2H), 3.83 (t, 1H), 1.40 (dd, 6H), 1.11 - 1.00 (m, 2H), 0.89 - 0.76 (m,
2H).nOe実験は、フッ素とCH2O−基との間のトランス関係を必要とする、フッ素含有炭素C−H(5.14−4.96(d,1H))とイソプロピル基との間の空間相互作用を明らかにした。MS m/z 388.0 [M+H]+ および MS m/z
409.9 [M+Na]+.
第2の溶出異性体を、白色固体としてのラセミ1−(((syn)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−イソプロポキシイソキノリン−6−カルボニトリル(500mg、収率56%)として収集した。1H NMR (400 MHz, DMSO-d6) δ 8.50 (s, 1H), 8.00 - 7.92 (m, 2H), 7.81
(s, 1H), 7.40 (d, 1H), 4.90 (td, 1H), 4.72 - 4.52 (m, 1H), 4.48 (dd, 1H), 4.27
- 4.17 (m, 1H), 3.73 (d, 1H), 1.38 (t, 6H), 1.09 - 0.96 (m, 4H).
ステップ9:ラセミ1−(((anti)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−イソプロポキシイソキノリン−6−カルボキサミドの分離
エナンチオマーを、分取キラルSFCクロマトグラフィーにより分離した。機器:SFC−200 カラム:Chiralpak AS 300×50mm I.D.、10um。移動相:200mL/分で超臨界CO2/MeOH(0.1%NH3H2O)=55/45、カラム温度:38℃。ノズル圧:100Bar。ノズル温度:60℃。エバポレーター温度:20℃。トリマー温度:25℃。
7.72 (br. s., 2H), 7.52 (s, 1H), 7.43 (d, 1H), 5.15 - 4.94 (m, 1H), 4.90 - 4.81
(m, 1H), 4.39 (d, 2H), 3.81 (br. s., 1H), 1.40 (dd, 6H), 1.06 (br. s., 2H),
0.83 (d, 2H). MS m/z 388.0 [M+H]+およびMS m/z 409.9 [M+Na]+.
1−(((4S,7R)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−イソプロポキシイソキノリン−6−カルボキサミド
7.72 (br. s., 2H), 7.52 (s, 1H), 7.43 (d, 1H), 5.15 - 4.94 (m, 1H), 4.90 - 4.81
(m, 1H), 4.39 (d, 2H), 3.81 (br. s., 1H), 1.40 (dd, 6H), 1.06 (br. s., 2H),
0.83 (d, 2H). MS m/z 388.1 [M+H]+およびMS m/z 410.0 [M+Na]+.
ラセミ1−(((syn)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−イソプロポキシイソキノリン−6−カルボキサミド
エナンチオマーを、分取キラルSFCクロマトグラフィーにより分離した。機器:SFC−200 カラム:Chiralpak AS 300×50mm I.D.、10μm。移動相:200mL/分で超臨界CO2/MeOH(0.1%NH3H2O)=55/45、カラム温度:38℃。ノズル圧:100Bar。ノズル温度:60℃。エバポレーター温度:20℃。トリマー温度:25℃。
7.77 - 7.67 (m, 3H), 7.41 (d, 1H), 4.86 (td, 1H), 4.72 - 4.52 (m, 1H), 4.46
(dd, 1H), 4.22 (dd, 1H), 3.73 (d, 1H), 1.37 (t, 6H), 1.08 - 0.93 (m, 4H). MS m/z 388.1 [M+H]+およびMS m/z
410.0 [M+Na]+.
1−(((4S,7S)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−イソプロポキシイソキノリン−6−カルボキサミド
7.77 - 7.67 (m, 3H), 7.41 (d, 1H), 4.86 (td, 1H), 4.72 - 4.52 (m, 1H), 4.46
(dd, 1H), 4.22 (dd, 1H), 3.73 (d, 1H), 1.37 (t, 6H), 1.08 - 0.93 (m, 4H). MS m/z [M+H]+ 387.9およびMS m/z [M+Na]+ 409.9.
1−(((4S,7R)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−メトキシイソキノリン−6−カルボキサミド
第1の画分(140mg)を、同じ方法で調製した別のバッチと混合し、フラッシュカラム(EtOAc:石油エーテル 40%〜55%)により精製して、335mgの早期画分(収率23%)を黄色固体として得た。この物質をカルボキサミドに転化させ、そのエナンチオマーをその段階で分離した。
ラセミ1−(((anti)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−メトキシイソキノリン−6−カルボニトリル
NMR (400 MHz, DMSO-d6) δ
8.97 (s, 1H), 8.54 (s, 1H), 7.99 (d, 1H), 7.63 (s, 1H), 7.43 (d, 1H), 5.18 -
4.96 (m, 1H), 4.47 - 4.38 (m, 1H), 4.37 - 4.29 (m, 1H), 4.05 (s, 3H), 3.84 (dd,
1H), 1.11 - 1.01 (m, 2H), 0.89 - 0.76 (m, 2H). MS m/z 342.0 [M+H]+.
ラセミ1−(((syn)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−メトキシイソキノリン−6−カルボニトリル
NMR (400 MHz, DMSO-d6) δ 9.03
(s, 1H), 8.51 (s, 1H), 7.98 (d, 1H), 7.81 (s, 1H), 7.41 (d, 1H), 4.70 - 4.52
(m, 1H), 4.49 (dd, 1H), 4.21 (dd, 1H), 4.01 (s, 3H), 3.74 (br. s., 1H), 1.10 -
0.97 (m, 4H). MS m/z 342.0 [M+H]+.
ステップ2:ラセミ1−(((anti)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−メトキシイソキノリン−6−カルボキサミドの調製
1−(((4S,7R)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−メトキシイソキノリン−6−カルボキサミド
(br. s., 1H), 7.53 (s, 1H), 7.44 (d, 1H), 5.18 - 4.97 (m, 1H), 4.44 - 4.31 (m,
2H), 3.98 (s, 3H), 3.82 (t, 1H), 1.11 - 1.01 (m, 2H), 0.90 - 0.75 (m, 2H). MS m/z 382.1 [M+Na]+.
1−(((4R,7S)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−メトキシイソキノリン−6−カルボキサミド
(br. s., 1H), 7.53 (s, 1H), 7.44 (d, 1H), 5.17 - 4.96 (m, 1H), 4.44 - 4.33 (m,
2H), 3.98 (s, 3H), 3.85 - 3.79 (m, 1H), 1.07 (d, 2H), 0.89 - 0.73 (m, 2H). MS m/z 382.1 [M+Na]+.
1−(((4R,7R)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−メトキシイソキノリン−6−カルボキサミド
1−(((4R,7R)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−メトキシイソキノリン−6−カルボキサミド。分析キラルSFCクロマトグラフィー:カラム:AD(250mm×30mm、5μm)、移動相:EtOH:CO2=30:70(0.1%NH4OH)。流速:60mL/分。波長:220nm。保持時間6.687分。1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.15 (s, 1H), 7.89 (d, 1H), 7.84 (br. s., 1H), 7.74
(s, 1H), 7.69 (br. s., 1H), 7.42 (d, 1H), 4.70 - 4.52 (m, 1H), 4.48 (dd, 1H),
4.23 (dd, 1H), 3.95 (s, 3H), 3.74 (br. s., 1H), 1.02 (br. s., 4H). MS m/z 359.9 [M+H]+.
1−(((4S,7S)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−メトキシイソキノリン−6−カルボキサミド
7.84 (br. s., 1H), 7.74 (s, 1H), 7.69 (br. s., 1H), 7.42 (d, 1H), 4.70 - 4.52
(m, 3H), 4.48 (d, 2H), 4.22 (br. s., 2H), 3.95 (s, 3H), 3.74 (br. s., 1H), 1.02
(br. s., 4H). MS m/z 360.0 [M+H]+.
4−(((2S,3R)−3−エチル−5−オキソピロリジン−2−イル)メトキシ)−6−メトキシイソキノリン−7−カルボキサミド
1H), 4.08 (q, 2H), 3.82 (s, 3H), 3.63 (s, 2H), 3.26 (s, 2H), 1.18 (t, 3H). MS m/z 304 [M+H]+.
ステップ2:エチルN−(3−ブロモ−4−メトキシベンジル)−N−[(4−メチルフェニル)スルホニル]グリシネートの調製
1H), 6.83 (d, 1H), 4.40 (s, 2H), 4.02 (q, 2H), 3.90 (s, 2H), 3.88 (s, 3H), 2.45
(s, 3H), 1.16 (t, 3H). MS m/z 477.8 [M+Na]+.
ステップ3:N−(3−ブロモ−4−メトキシベンジル)−N−[(4−メチルフェニル)スルホニル]グリシンの調製
7.17 (dd, 1H), 6.84 (d, 1H), 4.39 (s, 2H), 3.94 (s, 2H), 3.89 (s, 3H),
2.44-2.50 (m, 3H). MS m/z 449.7 [M+Na]+.
ステップ4:N−(3−ブロモ−4−メトキシベンジル)−N−[(4−メチルフェニル)スルホニル]グリシルクロリドの調製
ステップ5:7−ブロモ−6−メトキシ−2−[(4−メチルフェニル)スルホニル]−2,3−ジヒドロイソキノリン−4(1H)−オンの調製
7.27 (t, 2H), 4.44 (s, 2H), 4.00 (s, 2H), 3.90 (s, 3H), 2.40 (s, 3H).
ステップ6:7−ブロモ−6−メトキシイソキノリン−4−オールの調製
1H), 8.02 (s, 1H), 7.46 (s, 1H), 4.00 (s, 3H).
ステップ7:4−ヒドロキシ−6−メトキシイソキノリン−7−カルボニトリルの調製
8.11 (s, 1H), 7.52 (s, 1H), 4.04 (s, 3H). MS m/z 201
[M+H]+.
ステップ8:4−(((2S,3R)−3−エチル−5−オキソピロリジン−2−イル)メトキシ)−6−メトキシイソキノリン−7−カルボニトリルの調製
ステップ9:4−(((2S,3R)−3−エチル−5−オキソピロリジン−2−イル)メトキシ)−6−メトキシイソキノリン−7−カルボキサミドの調製
DMSO(4mL)中の4−(((2S,3R)−3−エチル−5−オキソピロリジン−2−イル)メトキシ)−6−メトキシイソキノリン−7−カルボニトリル(106mg、0.19mmol)の溶液に、K2CO3(128mg、0.93mmol)およびH2O2(147mg、水中30%w/w溶液、1.30mmol)を20℃で添加した。反応混合物を20℃で2時間撹拌し、次いで水(20mL)で希釈し、10:1 DCM/MeOH(4×25mL)で抽出した。合わせた有機相をブラインで洗浄し、Na2SO4で乾燥させ、濾過し、濃縮して、粗生成物を得、これをHPLCにより精製した。カラム:Phenomenex Gemini C18 250×21.2mm×8um、勾配時間:10分。移動相:水(アンモニア)中19%MeCN〜水(アンモニア)中39%MeCN。流速:30mL/分。波長:220nm、所望の画分を減圧下で濃縮して、所望の生成物(20mg)を白色固体として得た。1H NMR (400 MHz, MeOD) δ 8.86 (s, 1H), 8.59 (s, 1H), 8.08 (s, 1H),
7.54 (s, 1H), 4.46 (dd, 1H), 4.25 (dd, 1H), 4.14 - 4.07 (m, 2H), 4.11 (s, 3H),
2.78 - 2.63 (m, 1H), 2.58 - 2.46 (m, 1H), 2.45 - 2.33 (m, 1H), 1.80 - 1.67 (m,
1H), 1.60 - 1.45 (m, 1H), 1.03 (t, 3H). MS m/e 344.1
[M+H]+.
4−(((2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル)メトキシ)−6−メトキシイソキノリン−7−カルボキサミド
ステップ2:4−(((2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル)メトキシ)−6−メトキシイソキノリン−7−カルボキサミドの調製
DMSO(1mL)中の4−(((2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル)メトキシ)−6−メトキシイソキノリン−7−カルボニトリル(25mg、0.051mmol)の溶液に、K2CO3(35.2mg、0.255mmol)およびH2O2(40.5mg、水中30%w/w溶液、0.357mmol)を添加した。反応混合物を2時間撹拌した。反応混合物を水(15mL)で希釈し、10:1 DCM/MeOH(4×20mL)で抽出した。合わせた有機相をブラインで洗浄し、Na2SO4で乾燥させ、濾過し、濃縮して、粗生成物を得、これをHPLCにより精製した。カラム:Phenomenex Gemini C18 250×21.2mm×8um。勾配時間:11分。移動相:水(アンモニア)中19%MeCN〜水(アンモニア)中39%MeCN。流速:35mL/分、波長:220nm。所望の画分を減圧下で濃縮して、所望の生成物(15mg)を白色固体として得た。1H NMR (400 MHz, MeOD) δ 8.85 (s, 1H), 8.59 (s, 1H), 8.04 (s, 1H),
7.80 (s, 1H), 5.07 (d, 0.5H), 4.94 (d, 0.5H), 4.31 (d, 2H), 4.21 (dd, 1H), 2.85
- 2.67 (m, 1H), 1.88 - 1.64 (m, 2H), 1.12 (t, 3H). MS
m/e 383.9 [M+Na]+.
5−(((2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル)メトキシ)−3−メトキシ−2−ナフトアミド
7.40 (d, 1H), 7.33 - 7.23 (m, 1H), 7.01 (d, 1H), 3.99 (s, 3H).
ステップ2:[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メチルメタンスルホネートの調製
(d, Hz, 0.5H), 4.40 (dd, Hz, 1H), 4.11 (t, 1H), 4.04 - 3.94 (m, 1H), 2.57 -
2.48 (m, 1H), 2.48 - 2.37 (m, 1H), 1.76 - 1.48 (m, 1H), 1.63 (s, 3H), 1.09 (t,
3H).
ステップ3:5−(((2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル)メトキシ)−3−メトキシ−2−ナフトニトリルの調製
1H), 7.40 - 7.34 (m, 1H), 7.32 - 7.28 (m, 1H), 6.84 (d, 1H), 5.00 - 4.80 (m,
1H), 4.20 (d, 2H), 4.17 - 4.08 (m, 1H), 3.98 (s, 3H), 2.71 - 2.47 (m, 1H), 1.86
- 1.73 (m, 1H), 1.69 - 1.54 (m, 1H), 1.11 (t, 3H). MS m/e
342.9 [M+H]+.
ステップ4:5−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−3−メトキシナフタレン−2−カルボキサミドの調製
DMSO(5mL)中の5−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−3−メトキシナフタレン−2−カルボキサミド(430mg、1.26mmol)の溶液に、K2CO3(868mg、6.28mmol)およびH2O2(997mg、水中30%w/w溶液、8.79mmol)を添加した。2時間後、反応混合物をDCM(120mL)で希釈し、ブライン(2×40mL)、水(30mL)およびブライン(30mL)で洗浄し、Na2SO4で乾燥させ、濾過し、濃縮して、粗生成物を得、これをDCM(10mL)とすり混ぜた。混合物を濾過し、ケークを水(2×8mL)およびDCM(6mL)で洗浄した。ケークを収集し、真空中で乾燥させて、所望の生成物(330mg、収率73%)をオフホワイトの固体として得た。1H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 8.26 (s, 1H), 7.78 (br. s.,
1H), 7.73 (s, 1H), 7.63 (br. s., 1H), 7.52 (d, 1H), 7.29 (t, 1H), 7.02 (d, 1H),
5.03 - 4.80 (m, 1H), 4.20 - 4.00 (m, 3H), 3.96 (s, 3H), 2.72 - 2.53 (m, 1H),
1.71 - 1.53 (m,2), 1.01 (t, 3H). MS m/e 360.9 [M+H]+. MS m/e 382.8
[M+Na]+.
(3S,6R)−5−オキソ−2,3,4,5,6,7,9,10−オクタヒドロ−12,14−(エタンジイリデン)−3,6−メタノピリド[2,3−l][1,4,11,8]トリオキシアザシクロペンタデシン−19−カルボキサミド
3.60-3.57 (m, 2H), 3.45 (t, 1H), 3.04-2.98 (m, 1H), 2.32-2.25 (m, 1H),
1.87-1.79 (m, 1H), 1.62 (s, 3H), 1.45 (s, 3H). MS m/z
248.2 [M+H]+.
ステップ2:(3R,5S)−3−((2−クロロエトキシ)メチル)−5−(ヒドロキシメチル)ピロリジン−2−オンの調製
3.67 (m, 5H), 3.65 - 3.59 (m, 2H), 3.59 - 3.49 (m, 1H), 2.77 - 2.64 (m, 1H),
2.44 - 2.31 (m, 2H), 2.24 (t, 1H), 1.91 - 1.77 (m, 1H) MS m/z 207.9 [M+H]+.
ステップ3:1−クロロ−7−ヒドロキシイソキノリン−6−カルボニトリルの調製
7.85 (d, 1H), 7,68 (s, 1H). MS m/z 205.2 [M+H]+.
ステップ4:1−クロロ−7−((2−(トリメチルシリル)エトキシ)メトキシ)イソキノリン−6−カルボニトリルの調製
7.58 (d, 1H), 5.52 (s, 2H), 3.92 - 3.85 (m, 2H), 1.05 - 0.96 (m, 2H), 0.02 (s,
9H). MS m/z 334.1 [M+H]+.
ステップ5:1−(((2S,4R)−4−((2−クロロエトキシ)メチル)−5−オキソピロリジン−2−イル)メトキシ)−7−((2−(トリメチルシリル)エトキシ)メトキシ)イソキノリン−6−カルボニトリルの調製
7.34 (d, 1H), 5.60 - 5.49 (m, 2H), 4.63 (dd, 1H), 4.46 (dd, 1H), 4.23 - 4.14
(m, 1H), 3.91 (t, 2H), 3.82 - 3.76 (m, 1H), 3.76 - 3.67 (m, 3H), 3.66 - 3.61
(m, 2H), 2.83 - 2.74 (m, 1H), 2.60 - 2.49 (m, 1H), 2.09 - 1.98 (m, 1H), 0.99
(t, 2H), -0.01 (s, 9H). MS m/z 528.2 [M+Na]+.
ステップ6:1−(((2S,4R)−4−((2−クロロエトキシ)メチル)−5−オキソピロリジン−2−イル)メトキシ)−7−ヒドロキシイソキノリン−6−カルボニトリルの調製
(d, 1H), 7.82 (s, 1H), 7.35 (s, 1H), 7.18 (d, 1H), 4.81 (dd, 1H), 4.27 - 4.19
(m, 1H), 4.14 (q, 1H), 3.86 (dd, 1H), 3.75 - 3.65 (m, 3H), 3.61 - 3.48 (m, 2H),
2.86 (tt, 1H), 2.56 - 2.44 (m, 1H), 2.01 (td, 1H) MS m/z 373.9 [M-H]+および375.9 [M+H]+.
ステップ7:(3S,6R)−5−オキソ−2,3,4,5,6,7,9,10−オクタヒドロ−12,14−(エタンジイリデン)−3,6−メタノピリド[2,3−l][1,4,11,8]トリオキシアザシクロペンタデシン−19−カルボニトリルの調製
(s, 1H), 7.97 (d, 1H), 7.65 (s, 1H), 7.39 (d, 1H), 4.84 (d, 1H), 4.71 - 4.62
(m, 1H), 4.53 - 4.45 (m, 1H), 4.23 (d, 1H), 3.91 (t, 1H), 3.81 (d, 2H), 3.77
(d, 1H), 3.49 (d, 1H), 2.69 - 2.57 (m, 1H), 2.19 - 2.08 (m, 1H). MS m/z 340.2 [M+H]+.
ステップ8:(3S,6R)−5−オキソ−2,3,4,5,6,7,9,10−オクタヒドロ−12,14−(エタンジイリデン)−3,6−メタノピリド[2,3−l][1,4,11,8]トリオキシアザシクロペンタデシン−19−カルボキサミドの調製
DMSO−d6(1.0mL)中の(3S,6R)−5−オキソ−2,3,4,5,6,7,9,10−オクタヒドロ−12,14−(エタンジイリデン)−3,6−メタノピリド[2,3−l][1,4,11,8]トリオキシアザシクロペンタデシン−19−カルボニトリル(5.9mg、0.017mmol)の溶液に、K2CO3(9.6mg、0.068mmol)を添加した。懸濁液を約5分間撹拌し、次いで過酸化水素を添加した(0.01mL)。追加の2滴のH2O2溶液(約0.03mL)およびK2CO3(約15mg)を添加した。1.5時間後、追加の1滴のH2O2溶液(0.015mL)を添加した。1時間後、反応混合物をMe2Sでクエンチし、約15分間撹拌した。反応混合物を濾過し、HPLCにより精製して、表題化合物(1.8mg、収率30%)を得た。HPLC条件:残留物をDMSO(1mL)に溶解し、逆相HPLCにより精製した、カラム:Waters XBridge C18 19×100、5μ;移動相A:水中0.03%NH4OH(v/v);移動相B:アセトニトリル中0.03%NH4OH(v/v);勾配:10.5分間で95.0%H20/5.0%アセトニトリルから直線的に60.0%H20/40.0%アセトニトリルにし、0.5分間で60.0%H20/40.0%アセトニトリルから直線的に0%H20/100%アセトニトリルにし、11.0から12.0分まで0%H20/100%アセトニトリルに保持した。流速:25mL/分。分析QCカラム:Waters Atlantis dC18 4.6×50、5μ;移動相A:水中0.05%TFA(v/v);移動相B:アセトニトリル中0.05%TFA(v/v);勾配:4.0分間で95.0%H20/5.0%アセトニトリルから直線的に5%H20/95%アセトニトリルにし、5.0分まで5%H20/95%アセトニトリルに保持した。流速:2mL/分。保持時間、1.75分。1H NMR (600 MHz, DMSO-d6) δ 8.66 (s, 1H), 8.13 (s, 1H), 7.86 (d, 1H),
7.84 (br. s., 1H), 7.66 (s, 1H), 7.61 (br. s., 1H), 7.38 (d, 1H), 7.10 - 7.04
(m, 1H), 4.78 (d, 1H), 4.59 (dd, 1H), 4.43 (dd, 1H), 4.20 (d, 1H), 3.92 (t,
1H), 3.85 - 3.75 (m, 2H), 3.59 - 3.52 (m, 1H), 3.49 (dd, 1H), 3.43 (1Hは水により不明確), 2.66 - 2.60 (m, 1H), 2.57 - 2.51 (m, 1H), 2.18 - 2.09 (m, 1H). MS
m/z 358.1 [M+H]+.
7−メトキシ−1−[(3−オキソ−2−アザビシクロ[3.1.0]ヘキサ−1−イル)メトキシ]イソキノリン−6−カルボキサミド
1H), 5.21 (dd, 1H), 5.18-5.16 (m, 1H), 4.05 (s, 2H), 3.79 (s, 3H), 2.92 (t,
2H), 2.51-2.46 (m, 2H). MS m/z 192 [M+H]+
ステップ2:メチル[ブタ−3−エン−1−イル(4−メトキシベンジル)アミノ](オキソ)アセテートの調製
6.88 (d, 1H), 5.79-5.71 (m, 0.5H), 5.71-5.62 (m, 0.5H), 5.10-5.06 (m, 1H),
5.05-5.01 (m, 1H), 4.58 (s, 1H), 4.39 (s, 1H), 3.89 (s, 1.5H), 3.87 (s, 1.5H),
3.82 (s, 1.5H), 3.81 (s, 1.5H), 3.35 (dd, 1H), 3.25-3.21 (m, 1H), 2.35-2.30 (m,
1H), 2.30-2.25 (m, 1H). MS m/z 278 [M+H]+
ステップ3:N−(ブタ−3−エン−1−イル)−2−ヒドロキシ−N−(4−メトキシベンジル)アセトアミドの調製
6.87 (d, 1H), 5.82-5.73 (m, 0.5H), 5.72-5.63 (m, 0.5H), 5.10 (d, 1H), 5.07-5.02
(m, 1H), 4.62 (s, 1H), 4.29 (s, 1H), 4.22 (d, 1H), 4.21 (d, 1H), 3.82 (s,
1.5H), 3.81 (s, 1.5H), 3.68 (t, 0.5H), 3.65 (t, 0.5H), 3.51-3.45 (m, 1H),
3.13-3.08 (m, 1H), 2.35-2.30 (m, 1H), 2.29-2.24 (m, 1H). MS m/z 250 [M+H]+
ステップ4:N−(ブタ−3−エン−1−イル)−2−{[tert−ブチル(ジメチル)シリル]オキシ}−N−(4−メトキシベンジル)アセトアミドの調製
6.85 (d, 1H), 5.80-5.74 (m, 0.5H), 5.74-5.67 (m, 0.5H), 5.06 (d, 1H), 5.04-4.98
(m, 1H), 4.56 (s, 1H), 4.52 (s, 1H), 4.37 (s, 1H), 4.34 (s, 1H), 3.82 (s,
1.5H), 3.81 (s, 1.5H), 3.38 (t, 1H), 3.29 (t, 1H), 2.33-2.29 (m, 1H), 2.29-2.26
(m, 1H), 0.93 (s, 4.5H), 0.89 (s, 4.5H), 0.14 (s, 3H), 0.09 (s, 3H).
ステップ5:1−({[tert−ブチル(ジメチル)シリル]オキシ}メチル)−2−(4−メトキシベンジル)−2−アザビシクロ[3.1.0]ヘキサンの調製
4.05 (d, 1H), 3.80 (s, 3H), 3.69 (d, 1H), 3.18 (d, 1H), 2.89-2.81 (m, 1H),
1.97-1.84 (m, 2H), 1.77-1.68 (m, 1H), 1.29 (td, 1H), 0.89 (s, 9H), 0.85 (t,
1H), 0.49 (dd, 1H), 0.06 (s, 6H). MS m/z 348 [M+H]+
ステップ6:2−アザビシクロ[3.1.0]ヘキサ−1−イルメタノール塩酸塩の調製
(br. s., 1H), 3.83-3.76 (m, 1H), 3.65 (d, 1H), 3.30-3.24 (m, 1H), 2.94-2.81 (m,
1H), 2.08-1.91 (m, 2H), 1.65 (td, 1H), 1.10-1.05 (m, 1H), 0.87-0.80 (m, 1H).
ステップ7:tert−ブチル1−({[tert−ブチル(ジメチル)シリル]オキシ}メチル)−2−アザビシクロ[3.1.0]ヘキサン−2−カルボキシレートの調製
(br. s., 1H), 2.16-2.05 (m, 1H), 1.82-1.73 (m, 1H), 1.65-1.57 (m, 1H), 1.47 (s,
9H), 1.05 (dd, 1H), 0.88 (s, 9H), 0.64 (t, 1H), 0.04 (s, 6H).
ステップ8:tert−ブチル1−({[tert−ブチル(ジメチル)シリル]オキシ}メチル)−3−オキソ−2−アザビシクロ[3.1.0]ヘキサン−2−カルボキシレートの調製
2.49 (d, 1H), 1.55 (s, 9H), 1.53-1.45 (m, 1H), 1.10 (dd, 1H), 0.88 (s, 9H),
0.66 (t, 1H), 0.05 (s, 6H). MS m/z 242 [M-Boc+H]+
(LCMS条件下でBocの脱保護).
ステップ9:tert−ブチル(3−オキソ−2−アザビシクロ[3.1.0]ヘキサ−1−イル)メチルカーボネートの調製
1H), 2.77 (dd, 1H), 2.35 (d, 1H), 1.67-1.57 (m, 1H), 1.51 (s, 9H), 1.14 (dd,
1H), 0.72 (t, 1H). MS m/z 228 [M+H]+
ステップ10:7−メトキシ−1−[(3−オキソ−2−アザビシクロ[3.1.0]ヘキサ−1−イル)メトキシ]イソキノリン−6−カルボニトリルの調製
7.23 (d, 1H), 6.60 (br. s., 1H), 4.93 (d, 1H), 4.58 (d, 1H), 4.08 (s, 3H), 2.82
(dd, 1H), 2.41 (d, 1H), 1.79 - 1.72 (m, 1H), 0.89 (t, 1H), 0.74 (t, 1H). MS m/z 310 [M+H]+
ステップ11:7−メトキシ−1−[(3−オキソ−2−アザビシクロ[3.1.0]ヘキサ−1−イル)メトキシ]イソキノリン−6−カルボキサミドの調製
1H), 7.18 (d, 1H), 4.70 (d, 1H), 4.55-4.46 (m, 1H), 4.03-3.98 (m, 3H), 2.68
(dd, 1H), 2.27 (d, 1H), 1.65 (br. s., 1H), 1.22-1.10 (m, 1H), 0.67-0.59 (m,
1H). MS m/z 328 [M+H]+
このラセミ物質(29mg)をキラルクロマトグラフィーにより分離して、2つのエナンチオマーが得られた。
エナンチオマー1:淡黄色固体、12mg(100%ee)、MS m/z 350.1
[M+Na]+.エナンチオマー2:淡黄色固体、13mg(99.5%ee)。MS m/z,
328.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) d = 8.58 (s, 1H), 8.17 (s,
1H), 7.89 (d, 1H), 7.84 (br. s., 1H), 7.69 (br. s, 2H), 7.42 (d, 1H), 4.70 (d,
1H), 4.58 (d, 1H), 4.00 (s, 3H), 2.70 - 2.62 (m, 1H), 1.74 - 1.65 (m, 1H), 1.17
(dd1H), 0.61 (t, 1H)プロトン1個は、おそらく水と重複しており、不明確。
7−メトキシ−1−{[(1S,5S)−3−オキソ−2−アザビシクロ[3.1.0]ヘキサ−1−イル]メトキシ}イソキノリン−6−カルボキサミド
(d, 1H), 4.57-4.47 (m, 1H), 4.05-3.99 (m, 3H), 2.68 (dd, 1H), 2.26 (d, 1H),
1.63 (br. s., 1H), 1.22-1.11 (m, 1H), 0.66-0.58 (m, 1H). MS m/z 350 [M+Na]+.
7−メトキシ−1−{[(1R,5R)−3−オキソ−2−アザビシクロ[3.1.0]ヘキサ−1−イル]メトキシ}イソキノリン−6−カルボキサミド
(d, 1H), 4.56-4.47 (m, 1H), 4.03-3.97 (m, 3H), 2.69 (dd, 1H), 2.26 (d, 1H),
1.64 (br. s., 1H), 1.23-1.11 (m, 1H), 0.66-0.59 (m, 1H). MS m/z 328 [M+H]+.
5−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−3−メトキシ−1,6−ナフチリジン−2−カルボキサミド
NMR (DMSO-d6, 376 MHz): δ-77.0.
ステップ2:N−[(2,2−ジメチルプロパノイル)オキシ]−5−メトキシピリジン−3−カルボキサミドの調製
7.70 (br. s., 1H), 3.89 (s, 3H), 1.29 (s, 9H). MS m/z
253 [M+H]+.
ステップ3:N−[(2,2−ジメチルプロパノイル)オキシ]−5−メトキシピリジン−3−カルボキサミド1−オキシドの調製
7.33 (s, 1H), 3.88 (s, 3H), 1.28 (s, 9H). MS m/z 269.0
[M+H]+
ステップ4:3−メトキシ−6a,7,10,10a−テトラヒドロ−7,10−メタノベンゾ[h][1,6]ナフチリジン−5(6H)−オン1−オキシドの調製
1H), 6.45 - 6.41 (m, 1H), 6.19 - 6.16 (m, 1H), 3.86 (s, 3H), 3.61 (d, 1H), 3.22
(br. s., 1H), 3.07 (d, 1H), 2.92 (br. s., 1H), 1.38 - 1.33 (m, 1H), 1.29 - 1.24
(m, 1H). MS m/z 259 [M+H]+
ステップ5:3−メトキシ−1,6−ナフチリジン−5(6H)−オン1−オキシドの調製
1H), 7.34 (t, 1H), 6.99 (d, 1H), 3.91 (s, 3H). MS m/z
193 [M+H]+
ステップ6:3−メトキシ−5−オキソ−5,6−ジヒドロ−1,6−ナフチリジン−2−カルボニトリルの調製
1H), 6.63 (d, 1H), 4.08 (s, 3H). MS m/z 202 [M+H]+
ステップ7:5−クロロ−3−メトキシ−1,6−ナフチリジン−2−カルボニトリルの調製
4.18 (s, 3H). MS m/z 220 [M+H]+
ステップ8:5−クロロ−3−メトキシ−1,6−ナフチリジン−2−カルボキサミドの調製
1H), 7.90 (s, 1H), 7.84 (br. s., 1H), 4.04 (s, 3H). MS
m/z 238 [M+H]+
ステップ9:5−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−3−メトキシ−1,6−ナフチリジン−2−カルボキサミドの調製
DMF(1.24mL)中の(3S,4S,5S)−4−エチル−3−フルオロ−5−(ヒドロキシメチル)ピロリジン−2−オン(38mg、0.236mmol)および5−クロロ−3−メトキシ−1,6−ナフチリジン−2−カルボキサミド(59mg、0.25mmol)の溶液に、KHMDS(0.95mL、THF中1.0M、0.95mmol)を室温で添加した。混合物を50℃で加熱し、2時間撹拌した。次いで、反応物を冷却し、飽和NH4Cl水溶液でクエンチし、DCMで希釈した。水層をDCMで抽出し、合わせた有機層をブラインで洗浄し、Na2SO4で乾燥させた。粗物質を、DCM/MeOHで溶出するシリカゲルカラムクロマトグラフィーを使用して精製して、表題化合物をオフホワイトの固体(24mg、収率27%)として得た。1H NMR (DMSO-d6, 500 MHz): δ 8.93 (s, 1H), 8.11 (d, 1H), 8.06 (s, 1H),
8.02 (br. s., 1H), 7.73 (br. s., 1H), 7.44 (dd, 1H), 4.97-4.83 (m, 1H), 4.61
(dd, 1H), 4.23 (dd, 1H), 4.14-4.07 (m, 1H), 3.95 (s, 3H), 2.68-2.56 (m, 1H),
1.63-1.56 (m, 2H), 1.02 (t, 3H). MS m/z 364 [M+H]+.
1−(((2S,3S,4S)−4−フルオロ−3−メチル−5−オキソピロリジン−2−イル)メトキシ)−7−メトキシ−N−メチルイソキノリン−6−カルボキサミド
ステップ2:1−(((2S,3S,4S)−4−フルオロ−3−メチル−5−オキソピロリジン−2−イル)メトキシ)−7−メトキシ−N−メチルイソキノリン−6−カルボキサミドの調製
DCM(4mL)中の1−(((2S,3S,4S)−4−フルオロ−3−メチル−5−オキソピロリジン−2−イル)メトキシ)−7−メトキシイソキノリン−6−カルボン酸(70mg、0.20mmol)の溶液に、EDCI(62mg、0.32mmol)およびHOBT(46mg、0.34mmol)、続いてメチルアミン塩酸塩(41mg、0.60mmol)およびDIPEA(130mg、1.00mmol)を添加した。淡黄色反応混合物を室温で16時間撹拌した。反応混合物を30mLのEtOAcで希釈し、20mLの飽和NaHCO3水溶液で洗浄した。二相混合物を濾過し、3×8mLの水および3×6mLのMTBEで洗浄した。ケークを収集し、真空中で乾燥させて、1−(((2S,3S,4S)−4−フルオロ−3−メチル−5−オキソピロリジン−2−イル)メトキシ)−7−メトキシ−N−メチルイソキノリン−6−カルボキサミド(49mg、収率67%)を白色固体として得た。1H NMR (400 MHz, DMSO-d6) δ 8.76 (br. s., 1H), 8.35 (br. s., 1H), 8.12
(s, 1H), 7.91 (d, 1H), 7.71 (s, 1H), 7.43 (d, 1H), 5.03 - 4.82 (m, 1H), 4.57
(d, 1H), 4.33 - 4.22 (m, 1H), 4.04 (br. s., 1H), 3.96 (s, 3H), 2.91 (m, 1H),
2.82 (d, 3H), 1.09 (d, 3H). 19F NMR (376 MHz, DMSO -d6,) -200.80
(br. s., 1F). MS m/e 362.0 [M+H]+.
IRAK4酵素DELFIAアッセイ、プロトコールA。これは、600μMのATP(KM)におけるIRAK4阻害剤および対照化合物を特徴付けるために、ヒトIRAK4 FL(完全長)構造を用い、DELFIA(解離促進ランタニド蛍光免疫アッセイ、Perkin−Elmer)プラットフォームを利用してIRAK4酵素活性を測定するin vitroアッセイである。アッセイにおける酵素の最終量は0.1nMのIRAK4 FLであり、基質の最終濃度は50nMであり、DMSOの最終濃度は2.5%である。
Claims (12)
- 式IIc、IIe、IIf、IIg、IIh、IIi、IIl、IIm、IIn、IIo、IIp、IIq、IIr、IIs、IIt、IIu、IIv、またはIIx:
(式中、
R1は、C1〜C6アルキルまたは−(C1〜C6アルキル)n(C1〜C6シクロアルキル)であり、アルキルまたはシクロアルキルは、重水素、ハロゲン、CN、OH、またはC1〜C6アルコキシで置換されていてもよく、
R2は、水素であり、
R3は、水素、重水素、ハロゲン、ニトリル、−(CH2)tNR8aR8b、−(CH2)t(6〜10員アリール)、またはN、O、もしくはSから選択される1〜3個のヘテロ原子を有する−(CH2)t(5〜10員ヘテロアリール)であり、前記アリールまたはヘテロアリールは、1〜3個のC1〜C6アルキル、重水素、ハロゲン、CN、OH、ヒドロキシC1〜C6アルキル、またはC1〜C6アルコキシで置換されていてもよく、
R4aおよびR4bは、それぞれ独立に、水素、フッ素、OH、C1〜C3アルコキシ、またはCH2OR7であり、R7は、R1と一緒になり、ハロゲンまたはアルキルで置換されていてもよいC1〜C4アルキレンであり、
R5aおよびR5bは、独立に、水素、C1〜C3アルキル、もしくはC1〜C3−アルコキシであり、前記アルキルもしくはアルコキシは、1〜3個の重水素、ハロゲン、OH、もしくはCNで置換されていてもよく、またはR5aおよびR5bは、それらが結合している原子と一緒になり、C3〜C7シクロアルキルもしくはC3〜C7ヘテロシクロアルキルを形成し、前記シクロアルキルもしくはヘテロシクロアルキルは、1〜3個の重水素、ハロゲン、OH、CN、もしくはC1〜C3アルキルで置換されていてもよく、
R6は、水素もしくはC1〜C3アルキルであり、またはR5bおよびR6は、それらが結合している原子と一緒になり、C3〜C7シクロアルキルもしくはC3〜C7ヘテロシクロアルキルを形成し、前記シクロアルキルもしくはヘテロシクロアルキルは、1〜3個の重水素、ハロゲン、OH、CN、もしくはC1〜C3アルキルで置換されていてもよく、
R8aおよびR8bは、それぞれ独立に、水素、−S(O)2R9、または−C(O)R9であり、
R9は、C1〜C6アルキル、C1〜C6シクロアルキル、6〜10員アリール、または1〜3個のヘテロ原子を有する5〜10員ヘテロアリールであり、前記アルキル、シクロアルキル、アリール、またはヘテロアリールは、1〜3個のC1〜C6アルキル、ハロゲン、CN、OH、C1〜C6アルコキシ、またはC1〜C6ヒドロキシで置換されていてもよく、
nは、0または1であり、
tは、0、1、2、または3である)の化合物、または薬学的に許容できるその塩。 - R1が、C1〜C6アルキルであり、
R2が、水素であり、
R3が、水素、重水素、−(CH2)tNR8aR8b、−(CH2)t(6〜10員アリール)、またはN、O、もしくはSから選択される1〜3個のヘテロ原子を有する−(CH2)t(5〜10員ヘテロアリール)であり、前記アリールまたはヘテロアリールは、1〜3個のC1〜C6アルキル、重水素、ハロゲン、CN、OH、ヒドロキシC1〜C6アルキル、またはC1〜C6アルコキシで置換されていてもよく、
R6が、水素であり、
R8aおよびR8bが、それぞれ独立に、水素、−S(O)2R9、または−C(O)R9であり、
R9が、C1〜C6アルキル、C1〜C6シクロアルキル、6〜10員アリール、または1〜3個のヘテロ原子を有する5〜10員ヘテロアリールであり、前記アルキル、シクロアルキル、アリール、またはヘテロアリールは、1〜3個のC1〜C6アルキル、ハロゲン、CN、OH、C1〜C6アルコキシ、またはC1〜C6ヒドロキシで置換されていてもよく、
tが、0または1である、請求項1に記載の化合物、または薬学的に許容できるその塩。 - R3のアリールおよびヘテロアリールが、1個または2個のC1〜C6アルキルまたはC1〜C6ヒドロキシアルキルで置換されていてもよい、フェニル、ピラゾリル、イミダゾリル、およびオキサゾリルから選択される、請求項1または2に記載の化合物、または薬学的に許容できるその塩。
- R3が、水素、重水素、または−(CH2)tNR8aR8bであり、
R8aおよびR8bが、それぞれ独立に、水素または−S(O)2R9であり、
R9が、C1〜C6アルキル、C1〜C6シクロアルキル、6〜10員アリール、または1〜3個のヘテロ原子を有する5〜10員ヘテロアリールであり、前記アルキル、シクロアルキル、アリール、またはヘテロアリールは、1〜3個のC1〜C6アルキル、ハロゲン、CN、OH、C1〜C6アルコキシ、またはC1〜C6ヒドロキシで置換されていてもよく、
tが、0または1である、請求項1または2に記載の化合物、または薬学的に許容できるその塩。 - 8−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−2−メトキシキノリン−3−カルボキサミド;
4−(1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
4−(4−メチル−1H−イミダゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
4−(1−メチル−1H−ピラゾール−3−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
4−(1−メチル−1H−ピラゾール−4−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
4−(4−メチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
4−(4,5−ジメチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
4−[4−(ヒドロキシメチル)−1H−イミダゾール−2−イル]−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
4−(5−メチル−1,3−オキサゾール−2−イル)−1−{[(2S)−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−4−[(フェニルスルホニル)アミノ]−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)−4−[(ピリジン−3−イルスルホニル)アミノ]イソキノリン−6−カルボキサミド;
1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−4−[(1H−イミダゾール−4−イルスルホニル)アミノ]−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−4−{[(1−メチル−1H−イミダゾール−4−イル)スルホニル]アミノ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
4−{[(1,2−ジメチル−1H−イミダゾール−4−イル)スルホニル]アミノ}−1−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
4−アミノ−1−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−7−メトキシイソキノリン−6−カルボキサミド;
1−{[(4R,7S)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタ−4−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
1−{[(4S)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタ−4−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
1−{[(4R,7R)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタ−4−イル]メトキシ}−7−(プロパン−2−イルオキシ)イソキノリン−6−カルボキサミド;
1−(((4S,7R)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタン−4−イル)メトキシ)−7−イソプロポキシイソキノリン−6−カルボキサミド;
1−{[(4S,7R)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタ−4−イル]メトキシ}−7−メトキシイソキノリン−6−カルボキサミド;
1−{[(4R,7S)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタ−4−イル]メトキシ}−7−メトキシイソキノリン−6−カルボキサミド;
1−{[(4R,7R)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタ−4−イル]メトキシ}−7−メトキシイソキノリン−6−カルボキサミド;
1−{[(4S,7S)−7−フルオロ−6−オキソ−5−アザスピロ[2.4]ヘプタ−4−イル]メトキシ}−7−メトキシイソキノリン−6−カルボキサミド;
4−{[(2S,3R)−3−エチル−5−オキソピロリジン−2−イル]メトキシ}−6−メトキシイソキノリン−7−カルボキサミド;
4−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−6−メトキシイソキノリン−7−カルボキサミド;
5−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−3−メトキシナフタレン−2−カルボキサミド;
(3S,6R)−5−オキソ−2,3,4,5,6,7,9,10−オクタヒドロ−12,14−(エタンジイリデン)−3,6−メタノピリド[2,3−l][1,4,11,8]トリオキシアザシクロペンタデシン−19−カルボキサミド;
7−メトキシ−1−[(3−オキソ−2−アザビシクロ[3.1.0]ヘキサ−1−イル)メトキシ]イソキノリン−6−カルボキサミド;
7−メトキシ−1−{[(1S,5S)−3−オキソ−2−アザビシクロ[3.1.0]ヘキサ−1−イル]メトキシ}イソキノリン−6−カルボキサミド;
7−メトキシ−1−{[(1R,5R)−3−オキソ−2−アザビシクロ[3.1.0]ヘキサ−1−イル]メトキシ}イソキノリン−6−カルボキサミド;
5−{[(2S,3S,4S)−3−エチル−4−フルオロ−5−オキソピロリジン−2−イル]メトキシ}−3−メトキシ−1,6−ナフチリジン−2−カルボキサミド;および
1−{[(2S,3S,4S)−4−フルオロ−3−メチル−5−オキソピロリジン−2−イル]メトキシ}−7−メトキシ−N−メチルイソキノリン−6−カルボキサミド
から選択される化合物、または薬学的に許容できるその塩。 - 自己免疫疾患、炎症性疾患、自己炎症性状態、疼痛状態、呼吸、気道、および肺の状態、胃腸(GI)障害、アレルギー性疾患、感染症に基づく疾患、外傷および組織傷害に基づく状態、線維症疾患、IL1経路の過剰活性により主導される疾患、眼/眼球疾患、関節、筋肉、および骨の障害、皮膚/皮膚科学的疾患、腎疾患、遺伝子疾患、造血疾患、肝疾患、口腔疾患、糖尿病(例えばII型)およびその合併症を含む代謝疾患、増殖性疾患、心血管状態、血管状態、神経炎症状態、神経変性状態、癌、敗血症、肺の炎症および損傷、または肺高血圧症からなる群から選択される疾患または状態を治療するための、請求項1〜から5のいずれか一項に記載の化合物、または薬学的に許容できるその塩を含む医薬組成物。
- 疾患または状態が、全身性エリトマトーデス(SLE)、ループス腎炎、リウマチ性関節炎、乾癬、アトピー性皮膚炎、痛風、クリオピリン関連周期性症候群(CAPS)、びまん性大細胞型B細胞リンパ腫(DLBCL)、慢性腎疾患または急性腎損傷、慢性閉塞性肺障害(COPD)、喘息、および気管支痙攣からなる群から選択される、請求項6に記載の医薬組成物。
- 請求項1〜5のいずれか一項に記載の化合物、または薬学的に許容できるその塩と、薬学的に許容できるビヒクル、希釈剤、もしくは担体とを含む医薬組成物。
- 請求項1〜5のいずれか一項に記載の化合物、または薬学的に許容できるその塩である第1の化合物と、
コルチコステロイド、ヒドロキシクロロキン、シクロホスファミド、アザチオプリン、ミコフェノール酸モフェチル、メトトレキセート、ヤヌスキナーゼ阻害剤、スタチン、カルシポトリエン、アンギオテンシン変換酵素阻害剤、およびアンギオテンシン受容体遮断剤から選択される第2の化合物と、
任意選択の薬学的に許容できる担体、ビヒクル、または希釈剤と
を含む治療上有効な量の組成物を含む組合せ医薬。 - 第2の化合物が、ヤヌスキナーゼ阻害剤である、請求項9に記載の組合せ医薬。
- ヤヌスキナーゼ阻害剤が、ルキソリチニブ、バリシチニブ、トファシチニブ、デセルノチニブ、セルドゥラチニブ、JTE−052、ペフィシチニブ、GLPG−0634、INCB−47986、INCB−039110、PF−04965842、XL−019、ABT−494、R−348、GSK−2586184、AC−410、BMS−911543、およびPF−06263276から選択される、請求項10に記載の組合せ医薬。
- ヤヌスキナーゼ阻害剤が、トファシチニブである、請求項10に記載の組合せ医薬。
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Families Citing this family (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2910128T3 (es) * | 2014-04-04 | 2022-05-11 | Pfizer | Compuestos de heteroarilo o arilo fusionados con biciclo y su uso como inhibidores de IRAK4 |
DK3341367T3 (da) | 2015-08-27 | 2021-04-12 | Pfizer | Bicyklisk-fusionerede heteroaryl- eller arylforbindelser som irak4-modulatorer |
US11780848B2 (en) | 2015-10-16 | 2023-10-10 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1- carboxamide and solid state forms thereof |
SG11201802990RA (en) | 2015-10-16 | 2018-05-30 | Abbvie Inc | PROCESSES FOR THE PREPARATION OF (3S,4R)-3-ETHYL-4-(3H-IMIDAZO[1,2-a]PYRROLO[2,3-e]-PYRAZIN-8-YL)-N-(2,2,2-TRIFLUOROETHYL)PYRROLIDINE-1-CARBOXAMIDE AND SOLID STATE FORMS THEREOF |
US11524964B2 (en) | 2015-10-16 | 2022-12-13 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
US11512092B2 (en) | 2015-10-16 | 2022-11-29 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
US10550126B2 (en) | 2015-10-16 | 2020-02-04 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-A]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
US11365198B2 (en) | 2015-10-16 | 2022-06-21 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
JOP20180011A1 (ar) | 2017-02-16 | 2019-01-30 | Gilead Sciences Inc | مشتقات بيرولو [1، 2-b]بيريدازين |
PL3621960T3 (pl) * | 2017-05-11 | 2021-11-08 | Bristol-Myers Squibb Company | Tienopirydyny i benzotiofeny użyteczne jako inhibitory irak4 |
WO2019060693A1 (en) | 2017-09-22 | 2019-03-28 | Kymera Therapeutics, Inc. | CRBN LIGANDS AND USES THEREOF |
IL273432B (en) | 2017-09-22 | 2022-09-01 | Kymera Therapeutics Inc | Protein compounds and their uses |
JP2021509412A (ja) * | 2017-10-30 | 2021-03-25 | シンブリア セラピューティクス インクSynblia Therapeutics,Inc. | Irak4阻害剤およびその使用 |
WO2019111218A1 (en) | 2017-12-08 | 2019-06-13 | Cadila Healthcare Limited | Novel heterocyclic compounds as irak4 inhibitors |
US10874743B2 (en) | 2017-12-26 | 2020-12-29 | Kymera Therapeutics, Inc. | IRAK degraders and uses thereof |
US11512080B2 (en) | 2018-01-12 | 2022-11-29 | Kymera Therapeutics, Inc. | CRBN ligands and uses thereof |
US11485743B2 (en) | 2018-01-12 | 2022-11-01 | Kymera Therapeutics, Inc. | Protein degraders and uses thereof |
WO2019149522A1 (en) * | 2018-01-31 | 2019-08-08 | Merck Patent Gmbh | Quinoline compounds as irak inhibitors and uses thereof |
CN108853112B (zh) * | 2018-06-13 | 2021-02-02 | 四川理工学院 | 化合物或其在药学上可接受的盐在制备治疗痛风、高尿酸血症药物中的应用 |
US11292792B2 (en) | 2018-07-06 | 2022-04-05 | Kymera Therapeutics, Inc. | Tricyclic CRBN ligands and uses thereof |
TWI721483B (zh) | 2018-07-13 | 2021-03-11 | 美商基利科學股份有限公司 | 吡咯并[1,2-b]嗒𠯤衍生物 |
GB201902327D0 (en) * | 2019-02-20 | 2019-04-03 | Inflazome Ltd | Novel compounds |
KR102329235B1 (ko) | 2018-11-21 | 2021-11-22 | 한국화학연구원 | Irak4 저해제로서 신규의 삼중고리 화합물 |
WO2020106059A1 (ko) | 2018-11-21 | 2020-05-28 | 한국화학연구원 | Irak4 저해제로서 신규의 삼중고리 화합물 |
JP2022516401A (ja) | 2018-11-30 | 2022-02-28 | カイメラ セラピューティクス, インコーポレイテッド | Irak分解剤およびそれらの使用 |
MX2021007152A (es) | 2018-12-17 | 2021-11-03 | Vertex Pharma | Inhibidores de apol1 y sus metodos de uso. |
CN111662295B (zh) * | 2019-03-05 | 2021-09-10 | 珠海宇繁生物科技有限责任公司 | 一种irak4激酶抑制剂及其制备方法 |
WO2021011724A1 (en) * | 2019-07-18 | 2021-01-21 | Bristol-Myers Squibb Company | Tricyclic heteroaryl compounds useful as irak4 inhibitors |
MX2022004168A (es) * | 2019-10-07 | 2022-06-16 | De Shaw Res Llc | Compuestos aromaticos de arilmetileno a manera de bloqueadores del canal de potasio kv1.3. |
CN112679472A (zh) * | 2019-10-17 | 2021-04-20 | 北京桦冠医药科技有限公司 | 具有irak4抑制剂活性的异喹啉类化合物 |
MX2022005270A (es) * | 2019-11-01 | 2022-06-09 | Janssen Biotech Inc | Derivados de quinolina y quinoxalina fluoradas como inhibidores de dihidroorotato deshidrogenasa (dhodh) para el tratamiento del cancer, enfermedades autoinmunes e inflamatorias. |
US20220378707A1 (en) * | 2019-11-14 | 2022-12-01 | Pfizer Inc. | 1-(((2s,3s,4s)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl)methoxy)-7-methoxyisoquinoline-6-carboxamide combinations and oral dosage forms |
CN110845374A (zh) * | 2019-11-22 | 2020-02-28 | 北京振东光明药物研究院有限公司 | 比卡鲁胺杂质化合物及其制备方法、检测方法和应用 |
TW202136251A (zh) | 2019-12-17 | 2021-10-01 | 美商凱麥拉醫療公司 | Irak降解劑及其用途 |
US11591332B2 (en) | 2019-12-17 | 2023-02-28 | Kymera Therapeutics, Inc. | IRAK degraders and uses thereof |
WO2021158666A1 (en) * | 2020-02-04 | 2021-08-12 | Vertex Pharmaceuticals Incorporated | Solid forms of apol1 inhibitor and methods of using same |
IL296035A (en) | 2020-03-06 | 2022-10-01 | Vertex Pharma | Treatment methods for apol-1 dependent focal segmental tuberous sclerosis |
AU2021248720A1 (en) | 2020-04-04 | 2022-11-03 | Pfizer Inc. | Methods of treating coronavirus disease 2019 |
TW202210483A (zh) | 2020-06-03 | 2022-03-16 | 美商凱麥拉醫療公司 | Irak降解劑之結晶型 |
CR20230132A (es) | 2020-08-26 | 2023-06-27 | Vertex Pharma | Inhibidores de apol1 y métodos para usar los mismos |
US20230357271A1 (en) * | 2020-09-30 | 2023-11-09 | Asahi Kasei Pharma Corporation | Macrocyclic compound |
CN112694426B (zh) * | 2020-12-29 | 2022-11-04 | 山东铂源药业股份有限公司 | 一种阿普斯特中间体的合成方法 |
KR20220138655A (ko) * | 2021-04-06 | 2022-10-13 | 주식회사 온코크로스 | 신장 질환의 예방 또는 치료용 화합물 |
CN113995757B (zh) * | 2021-12-03 | 2023-03-14 | 合肥工业大学 | 罗沙司他在治疗偏头痛药物中的应用及含有罗沙司他的药物 |
CN115845064A (zh) * | 2022-02-17 | 2023-03-28 | 苏州大学 | 降低脑内铁含量的药物在制备治疗和/或预防神经精神疾病药物中的应用 |
CN114527213A (zh) * | 2022-02-22 | 2022-05-24 | 正大制药(青岛)有限公司 | 一种用于托匹司他的质量检测方法 |
WO2023235433A1 (en) * | 2022-06-01 | 2023-12-07 | Rigel Pharmaceuticals, Inc. | Bicyclic inhibitors of irak |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0028489B1 (en) | 1979-11-05 | 1983-10-05 | Beecham Group Plc | Enzyme derivatives, and their preparation |
AU680870B2 (en) * | 1993-04-28 | 1997-08-14 | Astellas Pharma Inc. | New heterocyclic compounds |
US5612359A (en) | 1994-08-26 | 1997-03-18 | Bristol-Myers Squibb Company | Substituted biphenyl isoxazole sulfonamides |
TW536540B (en) | 1997-01-30 | 2003-06-11 | Bristol Myers Squibb Co | Endothelin antagonists: N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide and N-(4,5-dimethyl-3-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4'-(2-oxazolyl)[1,1'-biphe |
AU767456B2 (en) | 1998-07-06 | 2003-11-13 | Bristol-Myers Squibb Company | Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists |
MY125533A (en) | 1999-12-06 | 2006-08-30 | Bristol Myers Squibb Co | Heterocyclic dihydropyrimidine compounds |
HU230302B1 (hu) * | 2000-10-20 | 2015-12-28 | Eisai R&D Management Co., Ltd. | Nitrogéntartalmú aromás származékok és ezeket tartalmazó gyógyászati készítmények |
DE60301491T2 (de) | 2002-02-27 | 2006-05-18 | Pfizer Products Inc., Groton | Acc-hemmer |
EP1724268A4 (en) * | 2004-02-20 | 2010-04-21 | Kirin Pharma Kk | COMPOUND HAVING TGF-BETA INHIBITING ACTIVITY AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME |
PT1753748E (pt) | 2004-05-12 | 2009-08-28 | Pfizer Prod Inc | Derivados de prolina e a sua utilização como inibidores de dipeptidil peptidase iv |
DK2463283T3 (da) | 2006-04-20 | 2014-08-18 | Pfizer Prod Inc | Kondenserede heterocykliske phenylamidoforbindelser til forebyggelse og behandling af glucokinase-medierede sygdomme |
MX2009005604A (es) | 2006-11-29 | 2009-06-08 | Pfizer Prod Inc | Inhibidores espiro cetona de acetil-coa carboxilasa. |
US20090036425A1 (en) | 2007-08-02 | 2009-02-05 | Pfizer Inc | Substituted bicyclolactam compounds |
JP2011521940A (ja) | 2008-05-28 | 2011-07-28 | ファイザー・インク | ピラゾロスピロケトンアセチルCoAカルボキシラーゼ阻害剤 |
WO2009144554A1 (en) | 2008-05-28 | 2009-12-03 | Pfizer, Inc. | Pyrazolospiroketone acetyl-c0a carboxylase inhibitors |
US20110130365A1 (en) | 2008-07-29 | 2011-06-02 | Benbow John W | Fluorinated Heteroaryls |
BRPI0918841B8 (pt) | 2008-08-28 | 2021-05-25 | Pfizer | derivados de dioxa-biciclo[3.2.1]octano-2,3,4-triol, seus cristais, composições farmacêuticas e usos |
TW201038580A (en) | 2009-02-02 | 2010-11-01 | Pfizer | 4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl derivatives |
EP2406230A1 (en) | 2009-03-11 | 2012-01-18 | Pfizer Inc. | Substituted indazole amides and their use as glucokinase activators |
RS52903B (en) | 2009-03-11 | 2014-02-28 | Pfizer Inc | BENZOFURANIL DERIVATIVES FOR USE AS GLUCOKINASE INHIBITORS |
WO2010106457A2 (en) | 2009-03-20 | 2010-09-23 | Pfizer Inc. | 3-oxa-7-azabicyclo[3.3.1]nonanes |
WO2010128425A1 (en) | 2009-05-08 | 2010-11-11 | Pfizer Inc. | Gpr 119 modulators |
US20120052130A1 (en) | 2009-05-08 | 2012-03-01 | Pfizer Inc. | Gpr 119 modulators |
NZ596467A (en) | 2009-06-05 | 2014-01-31 | Pfizer | L- ( piperidin-4-yl) -pyrazole derivatives as gpr 119 modulators |
WO2011005611A1 (en) | 2009-07-09 | 2011-01-13 | Merck Sharp & Dohme Corp. | Neuromedin u receptor agonists and uses thereof |
AU2012288969B2 (en) * | 2011-07-26 | 2017-02-23 | Boehringer Ingelheim International Gmbh | Substituted quinolines and their use as medicaments |
DE102014007350A1 (de) | 2013-10-11 | 2015-04-16 | Pfanner Schutzbekleidung Gmbh | Schutzhelm |
ES2910128T3 (es) * | 2014-04-04 | 2022-05-11 | Pfizer | Compuestos de heteroarilo o arilo fusionados con biciclo y su uso como inhibidores de IRAK4 |
BR112018002071A2 (pt) * | 2015-08-13 | 2018-09-18 | Pfizer | compostos heteroarílicos ou arílicos fundidos bicíclicos |
DK3341367T3 (da) | 2015-08-27 | 2021-04-12 | Pfizer | Bicyklisk-fusionerede heteroaryl- eller arylforbindelser som irak4-modulatorer |
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