JP2022523480A - ブルトン型チロシンキナーゼ阻害剤としての環状分子 - Google Patents
ブルトン型チロシンキナーゼ阻害剤としての環状分子 Download PDFInfo
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- JP2022523480A JP2022523480A JP2021542229A JP2021542229A JP2022523480A JP 2022523480 A JP2022523480 A JP 2022523480A JP 2021542229 A JP2021542229 A JP 2021542229A JP 2021542229 A JP2021542229 A JP 2021542229A JP 2022523480 A JP2022523480 A JP 2022523480A
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Abstract
Description
本発明は、小分子薬の分野に関し、具体的には、本発明は、タンパク質チロシンキナーゼ阻害活性を有する新しい分子、ならびにそのような化合物の合成および使用方法を提供する。
プロテインキナーゼは、500種を超えるタンパク質を含む、ヒト酵素の最大のファミリーである。ブルトン型チロシンキナーゼ(BTK)は、Tecファミリーのチロシンキナーゼのメンバーであり、初期B細胞の発達および成熟したB細胞活性化、シグナル伝達、および生存の調節剤である。BTKは、B細胞リンパ腫、白血病および自己免疫疾患の治療のための新しい分子標的になっている。従って、当技術分野は、より多くのBTK阻害活性を有する小分子化合物を提供することが急務となっている。
[発明が解決しようとする課題]
本発明の目的は、BTK阻害活性を有する小分子化合物を提供することである。
本発明の第1の態様は、以下の式(A)に示される化合物、またはその薬学的に許容される塩を提供し、
A環とB環とは、互いに並列に接続され、それぞれ独立して、置換または非置換の5-15員複素環またはヘテロ芳香環であり、
CyC1は、置換または非置換のC1-C6アルキル基(alkyl group)、置換または非置換のC3-C10シクロアルキル基(cycloalkyl group)、置換または非置換のC2-C6アルケニル基(alkenyl group)、置換または非置換のC3-C10シクロアルケニル基(cycloalkenyl group)、置換または非置換の5-15員複素環基(heterocyclyl group)、置換または非置換の5-15員ヘテロアリール基(heteroaryl group)、置換または非置換のC6-C10アリール基(aryl group)からなる群から選択され、
Cyc2は、置換または非置換のC1-C6アルキル基、置換または非置換のC3-C10シクロアルキル基、置換または非置換のC2-C6アルケニル基、置換または非置換のC3-C10シクロアルケニル基、置換または非置換の5-15員複素環基、置換または非置換の5-15員ヘテロアリール基、置換または非置換のC6-C10アリール基からなる群から選択され、
L1、L2は、それぞれ独立して、化学結合、N、O、S、-S(=O)、-S(=O)2、C(=O)、-C(O)nH-からなる群から選択され、
Zは、(CR2R3)nであり、nは、0、1、2,3、4、5または6であり、
Yは、(CR4R5)mであり、mは、0、1、2,3、4、5または6であり、
Uは、(CR6R7)rであり、rは、0、1、2または3であり、
n、mおよびrは、同時に0ではなく、
R2、R3、R4、R5、R6およびR7は、それぞれ独立して、H、NH2、OH、ハロゲン(halogen)、置換または非置換のC1-C6アルキル基からなる群から選択されるか、またはR2、R3、R4、R5、R6、R7およびR8のうちの任意の二つは、これに連結された炭素原子および間隔された環骨格原子とC3-C8炭素環、または4-8員複素環を共同に形成し、ここで、前記複素環のヘテロ原子は、S、O、またはNRfから選択され、Rfは、H、C1-C10アルキル基、C3-C10シクロアルキル基、C6-C20アリール基、またはC3-C14ヘテロアリール基であり、R2、R3、R4、R5、R6、R7、R8およびR9のうちの少なくとも一つは、OHまたは-[C(R10)(R11)]k-OHであり、
Wは、N、O、Sまたは化学結合からなる群から選択され、
Xは、-C(R8R9)-であり、
R8は、H、置換または非置換のC1-C6アルキル基、置換または非置換のC3-C10シクロアルキル基、置換または非置換のC6-C20アリール基、または置換または非置換のC3-C14ヘテロアリール基、CO2H、C(O)nRf 2からなる群から選択され、
R9は、H、OHまたは-[C(R10)(R11)]k-OHからなる群から選択され、
またはR8とR9とは、=Oを共同に構成し、
R8がHである場合、R9は、OHまたは-[C(R10)(R11)]k-OHであり、
R10およびR11は、それぞれ独立して、H、置換または非置換のC1-C6アルキル基、置換または非置換のC3-C10シクロアルキル基、置換または非置換のC6-C10アリール基、または置換または非置換のC3-C14ヘテロアリール基からなる群から選択されるか、またはR10およびR11は、これに連結された炭素原子とC3-C8炭素環、または4-8員複素環を共同に形成し、ここで、ヘテロ原子は、硫黄、酸素、またはNRfであり得、
kは、1、2,3、4、5または6であり、
特に明記しない限り、上記のヘテロ芳香環、ヘテロアリール基、複素環、複素環基は、それぞれ独立して、N、OおよびSから選択される1~4個のヘテロ原子を含み、
特に明記しない限り、前記置換とは、ハロゲン、C1-C6アルキル基、ハロゲン化C1-C6アルキル基、C1-C6アルコキシ基(alkoxy group)、ハロゲン化C1-C6アルコキシ基、C3-C8シクロアルキル基、ハロゲン化C3-C8シクロアルキル基、オキソ(Oxo)、-CN、ヒドロキシル基(hydroxyl group)、ヒドロキシ-C1-C6アルキル基、アミノ基(amino group)、カルボキシ基(carboxy group)、C6-C10アリール基、ハロゲン化C6-C10アリール基、もしくは、非置換またはハロゲン、フェニル基(phenyl group)からなる群から選択される置換基によって置換されたN、SおよびOから選択される1~3個のヘテロ原子を有する5-10員ヘテロアリール基からなる群から選択される一つまたは複数(例えば、2個、3個、4個等)の置換基によって置換される。
ここで、R12、R13、R14およびR15は、それぞれ独立して、H、ハロゲン、置換または非置換のC1-C6アルキル基、置換または非置換のC1-C6アルコキシ基、置換または非置換のC3-C10シクロアルキル基、置換または非置換のC3-C10的ヘテロシクロアルキル基であり、ヘテロ原子は、N、O、Sから選択され、
別の好ましい例において、L1-CyC1-L2-Cyc2は、
Vは、Nまたは-CR16-であり、ここで、R16は、H、ハロゲン置換または非置換のC1-C6アルキル基、置換または非置換のC3-C10シクロアルキル基からなる群から選択される。
ここで、破線は、化学結合であるか、またはなく、各A1、A2、A3、A4、A5、A6、A7、A8およびA9は、それぞれ独立して、O、S、N、NH、CHまたはCH2であり、
波線は、接続部位を表し、
上記基の各置換可能な部位は、置換基を含み得、ここで、置換基の定義は、上記のとおりである。
R12、R13、R14およびR15は、それぞれ独立して、H、ハロゲン、置換または非置換のC1-C6アルキル基、置換または非置換のC1-C6アルコキシ基、置換または非置換のC3-C10シクロアルキル基、置換または非置換の5-15員的複素環基からなる群から選択される。
R12、R13、R14およびR15は、それぞれ独立して、H、ハロゲン、置換または非置換のC1-C6アルキル基、置換または非置換のC1-C6アルコキシ基、置換または非置換のC3-C10シクロアルキル基、置換または非置換の5-15員的複素環基からなる群から選択され、
R16は、H、ハロゲン置換または非置換のC1-C6アルキル基、置換または非置換のC3-C10シクロアルキル基である。
2)(1S,3R)-3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール((1S,3R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexan-1-ol)(実施例2)
3)(1S,3R)-3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロヘキサン-1-オール/(1R,3R)-3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロヘキサン-1-オール(実施例3)((1S,3R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-methylcyclohexane-1-ol/(1R,3R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-methylcyclohexane-1-ol)
4)3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-(トリフルオロメチル)シクロヘキサン-1-オール(3-(4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-(trifluoromethyl)cyclohexane-1-ol)(実施例4)
5)3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロペンタノール(3-(4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-methylcyclopentanol)(実施例5)
6)3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロペンタノール(実施例6)
7)3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-(トリフルオロメチル)シクロペンタノール(3-(4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-(trifluoromethyl)cyclopentanol)(実施例7)
8)(1s,4s)-4-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール/(1r,4r)-4-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール((1s,4s)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexane-1-ol/(1r,4r)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexane-1-ol)
(実施例8)
9)(1s,4s)-4-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル]-1-メチルシクロヘキサン-1-オール/(1r,4r)-4(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル]-1-メチルシクロヘキサン-1-オール(実施例9)
10)4-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル]-1-シクロプロピルシクロヘキサン-1-オール(4-(4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-cyclopropylcyclohexane-1-ol)(実施例10)
11)(1s,4s)-4-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール/(1r,4r)-4-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール((1s,4s)-4-(4-amino-3-(4-(4-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexan-1-ol/(1r,4r)-4-(4-amino-3-(4-(4-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidine -1-yl)cyclohexan-1-ol)(実施例11)
12)(1s,4s)-4-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロヘキサン-1-オール((1s,4s)-4-(4-amino-3-(4-(4-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-methylcyclohexan-1-ol)および(1r,4r)-4-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロヘキサン-1-オール(実施例12)
13)シス-3-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロペンタン-1-オール(Cis-3-(4-amino-3-(4-(4-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclopentane-1-ol)およびトランス-3-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロペンタン-1-オール(実施例13)
14)(±)シス-3-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロペンタン-1-オール/(±)トランス-3-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロペンタン-1-オール((±)cis-3-(4-amino-3-(4-(4-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-Methylcyclopentan-1-ol/(±)trans-3-(4-amino-3-(4-(4-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d)pyrimidin-1-yl)-1-methylcyclopentan-1-ol)(実施例14)
15)(1R,3R)-3-(4-アミノ-3-(4-(3-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール((1R,3R)-3-(4-amino-3-(4-(3-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexane-1-ol)(実施例15)
16)(1R,3R)-3-(4-アミノ-3-(2-フルオロ-4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール((1R,3R)-3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexane-1-ol)(実施例16)
17)(1R,3R)-3-(4-アミノ-3-(4-(3-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール(実施例17)
18)(1R,3R)-3-(4-アミノ-3-(4-(2,6-ジフルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール((1R,3R)-3-(4-amino-3-(4-(2,6-difluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)Cyclohexan-1-ol)(実施例18)
19)(1R,3R)-3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール((1R,3R)-3-(4-amino-3-(4-(2-fluoro-3-methoxyphenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidine-1-yl)cyclohexan-1-ol)(実施例19)
20)(1s,4s)-4-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール(実施例20)
21)(1r,4r)-4-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール(実施例21)
22)シス-3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロペンタン-1-オール(cis-3-(4-amino-3-(4-(2-fluoro-3-methoxyphenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclopentane-1-ol)(実施例22)
23)トランス-3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロペンタン-1-オール(trans-3-(4-amino-3-(4-(2-fluoro-3-methoxyphenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclopentane-1-ol)(実施例23)
24)5-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)テトラヒドロ-2H-ピラン-3、4-ジオール(5-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)tetrahydro-2H-pyran-3,4-diol)(実施例24)
25)3-(4-アミノ-3-(4-(3-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロペンタン-1-オール(3-(4-amino-3-(4-(3-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclopentan-1-ol)(実施例25)
26)シス-3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール(cis-3-(4-amino-3-(4-(2-fluoro-3-methoxyphenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexane-1-ol)(実施例26)
27)3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1,2-ジオール(実施例27)
28)4-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1,2-ジオール(実施例28)
30)(5-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)テトラヒドロ-2H-ピラン-2-イル)メタノール((5-(4-amino-3-(4-(2-fluoro-3-methoxyphenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)tetrahydro-2H-pyran-2-yl)methanol)(実施例30)
31)(1R,3R)-3-(4-アミノ-3-(4-(2-フルオロ-3-(メトキシ-d3)フェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサノール((1R,3R)-3-(4-amino-3-(4-(2-fluoro-3-(methoxy-d3)phenoxy)phenyl)-1H-pyrazolo[3,4-d)pyrimidin-1-yl)cyclohexanol)(実施例31)
32)(1S、3S)-3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾリン[3,4-d]ピリミジン-1-イル)シクロヘキサノール((1S,3S)-3-(4-amino-3-(4-(2-fluoro-3-methoxyphenoxy)phenyl)-1H-pyrazoline[3,4-d]pyrimidine-1-yl)cyclohexanol)(実施例32)
33)3-(4-(4-アミノ-1-((1R,3R)-3-ヒドロキシシクロヘキシル)-1H-ピラゾロ[3,4-d]ピリミジン-3-イル)フェノキシ)-2-フルオロフェノール(3-(4-(4-amino-1-((1R,3R)-3-hydroxycyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenoxy)-2-Fluorophenol)(実施例33)
本発明の第2の態様は、(1)本発明の第1の態様に記載の化合物、またはその立体異性体または互変異性体、またはその薬学的に許容される塩、水和物または溶媒和物、および(2)薬学的に許容されるベクターを含む、医薬組成物を提供する。
本発明の範囲内で、本発明の上記の各技術的特徴と以下(例えば、実施例)に具体的に説明される各技術的特徴との間を、互いに組み合わせることにより、新しいまたは好ましい技術的解決策を構成することができることに理解されたい。スペースに限りがあるため、ここでは繰り返さない。
本明細書で使用される略語は、科学および生物学の分野では従来の意味を有する。
本発明の化合物は、一つまたは複数の不斉中心を含むため、ラセミ体およびラセミ混合物、単一のエナンチオマー、ジアステレオマー混合物および単一のジアステレオマーとして使用されることができる。本発明の化合物または式(A)の化合物に言及される場合、これらすべての異性体形態を含むことを理解されたい。
本明細書で使用されるように、「薬学的に許容される塩」という用語は、一般式Iの化合物の非毒性の酸またはアルカリ土類金属塩を指す。これらの塩は、一般式Iの化合物を最終的に分離および精製する際に調製することができるか、または適切な有機または無機酸または塩基をそれぞれ塩基性または酸性官能基と反応させることによって調製することができる。代表的な塩は、酢酸塩(acetate)、アジペート(adipate)、アルギン酸塩(alginate)、クエン酸塩(citrate)、アスパラギン酸塩(aspartate)、安息香酸塩(benzoate)、ベシル酸塩(benzenesulfonate)、重硫酸塩(bisulfate)、酪酸塩(butyrate)、樟脳酸塩(camphorate)、樟脳スルホン酸塩(camphorsulfonate)、ジグルコン酸塩(digluconate)、シクロペンタンプロピオン酸塩(cyclopentane propionate)、ドデシル硫酸塩(lauryl sulfate)、エタンスルホン酸塩(ethanesulfonate)、グルコースヘプタン酸塩(glucose heptanoate)、グリセロールリン酸塩(glycerophosphate)、ヘミ硫酸塩(hemisulfate)、エナント酸塩(heptanoate)、カプロン酸塩(caproate)、フマル酸塩(fumarate)、塩酸塩、臭化水素酸塩、ヨウ化水素酸塩、2-ヒドロキシルエタンスルホン酸塩(2-hydroxyethanesulfonate)、乳酸塩(lactate)、マレイン酸塩(maleate)、メタンスルホン酸塩(methanesulfonate)、ニコチン酸塩(nicotinate)、2-ナフチルスルホン酸塩(2-naphthylsulfonate)、シュウ酸塩(oxalate)、パモエート(pamoate)、ペクチン酸塩(pectinate)、チオシアン酸塩(thiocyanate)、3-フェニルプロピオン酸塩(3-phenylpropionate)、ピクリン酸塩(picrate)、ピバレート(pivalate)、プロピオン酸塩(propionate)、コハク酸塩(succinate)、硫酸塩(sulfate)、酒石酸塩(tartrate)、チオシアン酸塩(thiocyanate)、p-トルエンスルホン酸塩(p-toluenesulfonate)およびウンデカン酸塩(undecanoate)等を含むが、これらに限定されない。さらに、窒素を含む塩基性基は、例えば、メチル基、エチル基、プロピル基、ブチルクロリド、臭化物およびヨウ化物等のアルキルハロゲン化物、例えば、ジメチル基、ジエチル基、ジブチル基およびジペンチルサルフェート等のジアルキルサルフェート、例えば、デシル基、ラウリル基、ナツメグ基およびステアリル基の塩化物、臭化物およびヨウ化物等の長鎖ハロゲン化物、例えば、ベンジル基およびフェネチルブロミド等のアラルキルハロゲン化物等の試薬で四級化されることができる。これによって、水溶性または油溶性または分散性の生成物を得る。薬学的に許容される酸付加塩を形成するために使用できる酸の例としては、例えば、塩酸、硫酸、リン酸等の無機酸、および例えば、シュウ酸、マレイン酸、メタンスルホン酸、コハク酸、クエン酸等の有機酸を含む。塩基付加塩は、一般式Iの化合物の最終分離および精製中に原位置で調製されるか、またはカルボン酸部分を適切な塩基(例えば、薬学的に許容される金属陽イオンの水酸化物、炭酸塩または重炭酸塩)またはアンモニア、または有機第一級、第二級または第三級アミンとそれぞれ反応させることによって調製されることができる。薬学的に許容される塩は、例えば、ナトリウム、リチウム、カリウム、カルシウム、マグネシウム、およびアルミニウムの塩等のアルカリ金属およびアルカリ土類金属に基づく陽イオン、ならびに例えば、アンモニウム(ammonium)、テトラメチルアンモニウム(tetramethylammonium)、テトラエチルアンモニウム(tetraethylammonium)、メチルアミン(methylamine)、ジメチルアミン(dimethylamine)、トリメチルアミン(trimethylamine)、トリエチルアミン(triethylamine)、エチルアミン(ethylamine)等を含むがこれらに限定されない、非毒性アンモニウム、第四級アンモニウムおよびアミン陽イオンを含む。他の代表的な塩基付加塩を形成するために使用される有機アミンは、ジエチルアミン(diethylamine)、エチレンジアミン(ethylenediamine)、エタノールアミン(ethanolamine)、ジエタノールアミン(diethanolamine)、ピペラジン(piperazine)等を含む。
本発明の化合物は、BTKの異常活性およびBTK突然変異体(例えば、C481S)に関連する疾患を治療するために使用することができる。
本発明の化合物は、以下の反応式によって調製されることができる。
(1R,3R)-3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾール[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
1H NMR(400MHz、CDCl3):δ8.43-8.40(d、2H)、8.07(s、1H)、7.81-7.78(m、6H)、7.52-7.50(m、3H)、7.43-7.37(m、8H)、7.13-7.07(m、5H)、5.35(m、1H)、5.12-5.08(m、1H)、2.57-2.50(m、1H)、2.19-2.15(m、1H)、2.19(s、3H)、1.9-1.98(m、1H)、1.93-1.90(m、1H)、1.84-1.74(m、1H)、1.66-1.61(m、1H)、1.43-1.40(m、1H)。
1H NMR(400MHz、CDCl3):δ8.39(s、1H)、7.67-7.64(m、2H)、7.41-7.37(m、2H)、7.17-7.14(m、3H)、7.09-7.07(m、2H)、5.52(br-s、2H)、5.35-5.30(m、1H)、5.18-5.10(m、1H)、2.51-2.44(m、1H)、2.23-2.20(m、1H)、2.13(s、3H)、2.11-2.08(m、2H)、1.97-1.77(m、4H)、1.66-1.58(m、1H)。
(1S,3R)-3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
(1S,3R)-3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロヘキサン-1-オールおよび(1R,3R)-3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロヘキサン-1-オール
1H NMR(400MHz、Acetone-d6):δ8.25(s、1H)、7.76-7.74(m、2H)、7.46-7.42(m、2H)、7.21-7.16(m、3H)、7.13-7.11(m、2H)、6.36(br-s、2H)、4.97-4.89(m、1H)、3.96(br-s、1H)、2.29-2.23(m、1H)、2.01-1.86(m、4H)、1.74-1.71(m、1H)、1.62-1.56(m、2H)、1.35(s、3H)。
1H NMR(400MHz、Acetone-d6):δ8.24(s、1H)、7.76-7.74(m、2H)、7.46-7.42(m、2H)、7.21-7.15(m、3H)、7.13-7.11(m、2H)、6.32(br-s、2H)、5.27-5.19(m、1H)、3.49(br-s、1H)、2.18-2.12(m、1H)、1.98-1.91(m、4H)、1.72-1.69(m、2H)、1.49-1.41(m、1H)、1.29(s、3H)。
3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-(トリフルオロメチル)シクロヘキサン-1-オール
3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロペンタノール
3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロペンタノール
3-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-(トリフルオロメチル)シクロペンタノール
(1s,4s)-4-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オールおよび(1r,4r)-4-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
1H NMR(400MHz、CDCl3):δ8.38(s、1H)、7.67-7.63(m、2H)、7.40-7.39(m、2H)、7.19-7.07(m、5H)、5.46(br-s、2H)、4.84-4.76(m、1H)、3.86-3.79(m、1H)、2.28-2.05(m、6H)、1.57-1.56(m、2H)。
1H NMR(400MHz、CDCl3):δ8.43(s、1H)、7.48-7.41(m、2H)、7.40-7.39(m、2H)、7.28-7.27(m、1H)、7.24-7.16(m、4H)、5.24(br-s、2H)、4.22-4.16(m、1H)、3.91-3.86(m、1H)、2.45-2.35(m、2H)、2.14-2.11(m、2H)、1.95-1.92(m、2H)、1.40-1.31(m、2H)。
(1s,4s)-4-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル]-1-メチルシクロヘキサン-1-オールおよび(1r,4r)-4-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル]-1-メチルシクロヘキサン-1-オール
1H NMR(400MHz、CDCl3):δ8.37(s、1H)、7.66(d、J=8.6Hz、2H)、7.39(t、J=8.0Hz、2H)、7.16(dd、J=12.2Hz、8.0Hz、3H)、7.08(d、J=7.7Hz、2H)、5.49(br-s、2H)、4.79-4.72(m、1H)、2.55-2.45(m、2H)、1.94-1.79(m、4H)、1.75-1.67(m、2H)、1.32(s、3H)。
1H NMR(400MHz、CDCl3):δ8.37(s、1H)、7.65(d、J=8.7Hz、2H)、7.39(dd、J=8.5、7.5Hz、2H)、7.21-7.12(m、3H)、7.08(dd、J=8.6、1.0Hz、2H)、5.53(s、2H)、4.91-4.76(m、1H)、2.33-2.18(m、2H)、2.09-2.01(m、2H)、1.92(d、J=12.8Hz、2H)、1.77(dd、J=13.1,3.8Hz、2H)、1.43(s、3H)。
4-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル]-1-シクロプロピルシクロヘキサン-1-オール
(1s,4s)-4-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オールおよび(1r,4r)-4-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
1H NMR(400MHz、CDCl3):δ8.34(s、1H)、7.66(d、J=8.7Hz、2H)、7.10-7.06(m、6H)、5.90(br-s、2H)、4.83-4.78(m、1H)、4.12(m、1H)、2.55-2.49(m、2H)、2.01(m、2H)、2.42-2.41(m、2H)、2.04-1.99(m、2H)。
1H NMR(400MHz、CDCl3):δ8.38(s、1H)、7.64(d、J=8.7Hz、2H)、7.12-7.05(m、6H)、5.45(br-s、2H)、4.82-4.76(m、1H)、3.86-3.75(m、2H)、2.27-2.05(m、7H)。
(1s,4s)-4-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロヘキサン-1-オールおよび(1r,4r)-4-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロヘキサン-1-オール
1H NMR(400MHz、CDCl3):δ8.34(s、1H)、7.66-7.64(d、2H)、7.12-7.05(m、6H)、5.73(br-s、2H)、4.79-4.71(m、1H)、2.54-2.44(m、2H)、1.91-1.84(m、4H)、1.72-1.66(m、2H)、1.32(s、3H)。
1H NMR(400MHz、CDCl3):δ8.37(s、1H)、7.66-7.64(d、2H)、7.13-7.06(m、6H)、5.58(br-s、2H)、4.88-4.80(m、1H)、2.30-2.20(m、2H)、2.07-2.03(m、2H)、1.93-1.90(m、2H)、1.79-1.72(m、2H)、1.43(s、3H)。
(±)シス-3-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロペンタン-1-オールおよび(±)トランス-3-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロペンタン-1-オール
1H NMR(400MHz、CDCl3):δ8.38(s、1H)、7.63(m、2H)、7.15-6.97(m、6H)、5.56(br-s、2H)、5.47(m、1H)、4.44(s、1H)、2.52-2.34(m、2H)、2.32-2.16(m、1H)、2.20(m、1H)、2.12-2.00(m、1H)、1.92-1.81(m、1H)。
MS ESI:m/z=406、[M+H]+。
(±)シス-3-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロペンタン-1-オールおよび(±)トランス-3-(4-アミノ-3-(4-(4-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)-1-メチルシクロペンタン-1-オール
1H NMR(400MHz、CDCl3):δ8.39(s、1H)、7.67-7.65(m、2H)、7.13-7.05(m、6H)、5.64(br-s、2H)、5.54-5.48(m、1H)、2.49-2.41(m、1H)、2.39-2.33(m、2H)、2.22-2.18(m、1H)、2.08-2.02(m、1H)、1.80-1.69(m、1H)、1.45(s、3H)。
1H NMR(400MHz、CDCl3):δ8.37(s、1H)、7.66-7.64(m、2H)、7.13-7.03(m、6H)、5.71-5.63(m、1H)、5.49(br-s、2H)、2.52-2.37(m、1H)、2.29-2.26(m、1H)、2.25-2.13(m、3H)、1.88-1.83(m、1H)、1.52(s、3H)。
(1R,3R)-3-(4-アミノ-3-(4-(3-フルオロフェノキシ)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
(1R,3R)-3-(4-アミノ-3-(2-フルオロ-4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
(1R,3R)-3-(4-アミノ-3-(4-(2-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
(1R,3R)-3-(4-アミノ-3-(4-(2,6-ジフルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
(1R,3R)-3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
(1s,4s)-4-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
(1r,4r)-4-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロペンタン-1-オール
(±)トランス-3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロペンタン-1-オール
5-(4-アミノ-3-(4-フェノキシフェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)テトラヒドロ-2H-ピラン-3、4-ジオール
3-(4-アミノ-3-(4-(3-フルオロフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロペンタン-1-オール
シス-3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1-オール
3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1,2-ジオール
4-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサン-1,2-ジオール
1H NMR(400MHz、CDCl3)δ8.38(s、1H)、7.65-7.61(m、2H)、7.14-7.11(m、2H)、7.09-7.05(m、1H)、6.86-6.82(m、1H)、6.76-6.72(m、1H)、5.52(s、2H)、5.14-4.97(m、1H)、4.44(brs、1H)、3.96-3.94(m、4H)、3.86-3.80(m、1H)、2.67-2.61(m、1H)2.57-2.48(m、1H)、2.25-2.19(m、2H)、1.94-1.84(m、2H)、1.73-1.66(m、1H)。
1H NMR(400MHz、CDCl3)δ8.37(s、1H)、7.64-7.60(m、2H)、7.14-7.10(m、2H)、7.08-7.04(m、1H)、6.86-6.82(m、1H)、6.76-6.71(m、1H)、5.39(s、2H)、5.26-5.20(m、1H)、4.22(brs、1H)、3.99(m、3H)、3.87-3.84(m、1H)、2.42-2.36(m、1H)、2.31-2.35(m、2H)、2.17-2.06(m、2H)、1.96-1.88(m、2H)。
1-シクロヘキシル-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-4-アミン
ロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-4-アミン(190mg、0.44mmol)を20mlのメタノールに溶解し、10%湿ったパラジウム炭素(20mg)を加え、水素ガス(15psi)を3回置換した後、室温下で一晩反応させる。珪藻土でろ過し、ろ液を濃縮して残留物を得、残留物を分取HPLCで精製して、130mgの生成物を得、収率は、68%である。
(5-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)テトラヒドロ-2H-ピラン-2-イル)メタノール
1H NMR(400MHz、CDCl3):δ8.34(s、1H)、7.68-7.65(m、4H)、7.62-7.60(m、2H)、7.41-7.32(m、6H)、7.11-7.09(m、2H)、7.07-7.04(m、1H)、6.86-6.82(m、1H)、6.76-6.72(m、1H)、5.57(brs、2H)、4.83-4.82(m、1H)、4.49-4.45(m、1H)、3.94(s、3H)、3.87-3.82(m、2H)、3.71-3.69(m、2H)、2.62-2.57(m、1H)、2.28-2.22(m、1H)、2.14-2.08(m、1H)、1.82(m、1H)、1.03(s、9H)。
1H NMR(400MHz、CDCl3):δ8.36(s、1H)、7.71-7.68(m、4H)、7.64-7.61(m、2H)、7.44-7.37(m、6H)、7.14-7.12(m、2H)、7.09-7.04(m、1H)、6.86-6.81(m、1H)、6.76-6.72(m、1H)、5.51(brs、2H)、4.97-4.92(m、1H)、4.16-4.11(m、1H)、4.00-3.94(m、1H)、3.93(s、3H)、3.81-3.77(m、1H)、3.66-3.60(m、2H)、2.46-2.36(m、1H)、2.26-2.23(m、1H)、1.95(m、1H)、1.70-1.60(m、1H)、1.07(s、9H)。
1H NMR(400MHz、CDCl3):δ8.35(s、1H)、7.65-7.63(m、2H)、7.13-7.05(m、3H)、6.86-6.82(m、1H)、6.77-6.72(m、1H)、5.73(s、2H)、4.89(s、1H)、4.57-4.54(m、1H)、3.97-3.93(m、1H)、3.93(s、3H)、3.74-3.66(m、3H)、2.61-2.56(m、1H)、2.33-2.30(m、1H)、2.20-2.00(m、1H)、1.57-1.59(m、1H)。
1H NMR(400MHz、CDCl3):δ8.37(s、1H)、7.65-7.63(m、2H)、7.13-7.05(m、3H)、6.86-6.82(m、1H)、6.77-6.72(m、1H)、5.73(s、2H)、4.89(s、1H)、4.57-4.54(m、1H)、3.97-3.93(m、1H)、3.93(s、3H)、3.74-3.66(m、3H)、2.61-2.56(m、1H)、2.33-2.30(m、1H)、2.20-2.00(m、1H)、1.57-1.59(m、1H)。
1H NMR(400MHz、CDCl3):δ8.35(s、1H)、7.63-7.60(m、2H)、7.14-7.05(m、3H)、6.87-6.83(m、1H)、6.74-6.72(m、1H)、5.74(s、2H)、4.89-4.63(m、1H)、4.20-4.16(m、1H)、4.03-3.97(m、1H)、3.97(s、3H)、3.71-3.58(m、3H)、2.46-2.42(m、1H)、2.27-2.24(m、1H)、1.83-1.80(m、1H)、1.73-1.72(m、1H)。
1H NMR(400MHz、CDCl3):δ8.35(s、1H)、7.63-7.60(m、2H)、7.14-7.05(m、3H)、6.87-6.83(m、1H)、6.74-6.72(m、1H)、5.74(s、2H)、4.89-4.63(m、1H)、4.20-4.16(m、1H)、4.03-3.97(m、1H)、3.97(s、3H)、3.71-3.58(m、3H)、2.46-2.42(m、1H)、2.27-2.24(m、1H)、1.83-1.80(m、1H)、1.73-1.72(m、1H)。
(1R,3R)-3-(4-アミノ-3-(4-(2-フルオロ-3-(メトキシ-d3)フェノキシ)フェニル)-1H-ピラゾロ[3,4-d]ピリミジン-1-イル)シクロヘキサノール
(1S、3S)-3-(4-アミノ-3-(4-(2-フルオロ-3-メトキシフェノキシ)フェニル)-1H-ピラゾリン[3,4-d]ピリミジン-1-イル)シクロヘキサノール
(1R,3R)-3-(4-(4-アミノ-1-(3-ヒドロキシシクロヘキシル)-1H-ピラゾロ[3,4-d]ピリミジン-3-イル)フェノキシ)-2-フルオロフェノール
式Aの化合物のBTK/BTK(C481S)阻害活性は、米国ペンシルベニア州マルバーンのグランドキャニオンロードにある反応生物会社(Reaction Biology Corporation、One Great Valley Parkway、Malvern、PA、USA)によって測定される。ヒト完全長のBTK/BTK(C481S)酵素を使用し、基質は、20μMのペプチド基質[KVEKIGEGTYGVVYK]である。測定用のATP濃度は、10μMであり、スタウロスポリンを標準品として使用し、IC50は、3.94nMである。
ヒトびまん性大細胞型Bリンパ腫のTMD8細胞NOD/SCIDマウスの皮下移植腫瘍モデルにおいて、腫瘍増殖に対する実施例1の阻害作用を検出し、腫瘍体積および動物体重は、以下の図1および図2に示される。実施例1の30mg/kgの投与量の1日1回の経口投与またはまたは10→5mg/kgの投与量の1日2回の経口投与は、TMD8皮下移植腫瘍の増殖に対して有意な阻害効果を有し、22日投与後の腫瘍増殖の阻害率(TGI)は、それぞれ49.6%および52.7%である。実施例1の30mg/kgの投与量の1日1回の経口投与は、動物の体重に有意な影響を及ぼさず、10mg/kgの投与量の1日2回の経口投与は、8日間の連続投与後、動物の体重が減少したため、投与量を5mg/kgに調整し、引き続き14日間投与した。
Claims (10)
- 以下の式(A)に示される化合物、またはその薬学的に許容される塩であって、
A環とB環とは、互いに並列に接続され、それぞれ独立して、置換または非置換の5-15員複素環またはヘテロ芳香環であり、
CyC1は、置換または非置換のC1-C6アルキル基(alkyl group)、置換または非置換のC3-C10シクロアルキル基(cycloalkyl group)、置換または非置換のC2-C6アルケニル基(alkenyl group)、置換または非置換のC3-C10シクロアルケニル基(cycloalkenyl group)、置換または非置換の5-15員複素環基(heterocyclyl group)、置換または非置換の5-15員ヘテロアリール基(heteroaryl group)、置換または非置換のC6-C10アリール基(aryl group)からなる群から選択され、
Cyc2は、置換または非置換のC1-C6アルキル基、置換または非置換のC3-C10シクロアルキル基、置換または非置換のC2-C6アルケニル基、置換または非置換のC3-C10シクロアルケニル基、置換または非置換の5-15員複素環基、置換または非置換の5-15員ヘテロアリール基、置換または非置換のC6-C10アリール基からなる群から選択され、
L1、L2は、それぞれ独立して、化学結合、N、O、S、-S(=O)、-S(=O)2、C(=O)、-C(O)NH-からなる群から選択され、
Zは、(CR2R3)nであり、nは、0、1、2,3、4、5または6であり、
Yは、(CR4R5)mであり、mは、0、1、2,3、4、5または6であり、
Uは、(CR6R7)rであり、rは、0、1、2または3であり、
n、mおよびrは、同時に0ではなく、
R2、R3、R4、R5、R6およびR7は、それぞれ独立して、H、NH2、OH、ハロゲン(halogen)、置換または非置換のC1-C6アルキル基からなる群から選択されるか、またはR2、R3、R4、R5、R6、R7およびR8のうちの任意の二つは、これに連結された炭素原子および間隔された環骨格原子とC3-C8炭素環、または4-8員複素環を共同に形成し、ここで、前記複素環のヘテロ原子は、S、O、またはNRfから選択され、Rfは、H、C1-C10アルキル基、C3-C10シクロアルキル基、C6-C20アリール基、またはC3-C14ヘテロアリール基であり、R2、R3、R4、R5、R6、R7、R8およびR9のうちの少なくとも一つは、OHまたは-[C(R10)(R11)]k-OHであり、
Wは、N、O、Sまたは化学結合からなる群から選択され、
Xは、-C(R8R9)-であり、
R8は、H、置換または非置換のC1-C6アルキル基、置換または非置換のC3-C10シクロアルキル基、置換または非置換のC6-C20アリール基、または置換または非置換のC3-C14ヘテロアリール基、CO2H、C(O)nRf 2からなる群から選択され、
R9は、H、OHまたは-[C(R10)(R11)]k-OHからなる群から選択され、
またはR8とR9とは、=Oを共同に構成し、
R8がHである場合、R9は、OHまたは-[C(R10)(R11)]k-OHであり、
R10およびR11は、それぞれ独立して、H、置換または非置換のC1-C6アルキル基、置換または非置換のC3-C10シクロアルキル基、置換または非置換のC6-C10アリール基、または置換または非置換のC3-C14ヘテロアリール基からなる群から選択されるか、またはR10およびR11は、これに連結された炭素原子とC3-C8炭素環、または4-8員複素環を共同に形成し、ここで、ヘテロ原子は、硫黄、酸素、またはNRfであり得、
kは、1、2,3、4、5または6であり、
特に明記しない限り、上記のヘテロ芳香環、ヘテロアリール基、複素環、複素環基は、それぞれ独立して、N、OおよびSから選択される1~4個のヘテロ原子を含み、
特に明記しない限り、前記置換とは、ハロゲン、C1-C6アルキル基、ハロゲン化C1-C6アルキル基、C1-C6アルコキシ基(alkoxy group)、ハロゲン化C1-C6アルコキシ基、C3-C8シクロアルキル基、ハロゲン化C3-C8シクロアルキル基、オキソ(Oxo)、-CN、ヒドロキシル基(hydroxyl group)、ヒドロキシ-C1-C6アルキル基、アミノ基(amino group)、カルボキシ基(carboxy group)、C6-C10アリール基、ハロゲン化C6-C10アリール基、もしくは、非置換またはハロゲン、フェニル基(phenyl group)からなる群から選択される置換基によって置換されたN、SおよびOから選択される1~3個のヘテロ原子を有する5-10員ヘテロアリール基からなる群から選択される一つまたは複数(例えば、2個、3個、4個等)の置換基によって置換されることを特徴とする、化合物。 - 医薬組成物であって、
(1)請求項1~7のいずれか1項に記載の化合物、またはその立体異性体または互変異性体、またはその薬学的に許容される塩、水和物または溶媒和物、および(2)薬学的に許容されるベクターを含むことを特徴とする、医薬組成物。 - 請求項1~7のいずれか1項に記載の化合物、またはその立体異性体または互変異性体、またはその薬学的に許容される塩、水和物または溶媒和物または請求項6に記載の医薬組成物の用途であって、
BTKの異常活性およびBTK突然変異体(例えば、C481S)の異常活性に関連する疾患を予防および/または治療するための薬物の調製に使用されることを特徴とする、用途。 - 前記疾患または病症は、膀胱がん、脳腫瘍、乳がん、子宮がん、結腸直腸がん、食道がん、肝臓がん、濾胞性リンパ腫、黒色腫、血液悪性腫瘍、骨髄腫、卵巣がん、非小細胞肺がん、前立腺がん、小細胞肺がん、およびB-細胞来源的リンパ性悪性腫瘍、B細胞増殖性病症:びまん性B細胞リンパ腫、濾胞性リンパ腫、慢性リンパ性リンパ腫、慢性リンパ性白血病、B細胞若年リンパ球性白血病、リンパ性形質細胞リンパ腫/ヴァルデンストロムマクログロブリン血症、脾辺縁帯リンパ腫、形質細胞骨髄腫、形質細胞腫、結節外辺縁帯B細胞リンパ腫、結節内辺縁帯B細胞リンパ腫、マントル細胞リンパ腫、縦隔(胸腺)大細胞型B細胞リンパ腫、血管内大細胞型B細胞リンパ腫、原発性滲出性リンパ腫、バーキットリンパ腫/白血病またはリンパ腫様肉芽腫症から選択されることを特徴とする
請求項9に記載の用途。
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Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004531513A (ja) * | 2001-03-22 | 2004-10-14 | アボット ゲーエムベーハー ウント カンパニー カーゲー | 治療剤としてのピラゾールピリミジン |
JP2007520559A (ja) * | 2004-02-03 | 2007-07-26 | アボット・ラボラトリーズ | 治療薬としてのアミノベンゾオキサゾール類 |
JP2009520028A (ja) * | 2005-12-19 | 2009-05-21 | オーエスアイ・ファーマスーティカルズ・インコーポレーテッド | Igfr抑制剤および抗癌剤の併用 |
JP2010235628A (ja) * | 2006-09-22 | 2010-10-21 | Pharmacyclics Inc | ブルートンチロシンキナーゼ阻害剤 |
JP2013507448A (ja) * | 2009-10-12 | 2013-03-04 | ファーマサイクリクス,インコーポレイテッド | ブルトン型チロシンキナーゼの阻害剤 |
JP2014520866A (ja) * | 2011-07-19 | 2014-08-25 | メルク・シャープ・アンド・ドーム・コーポレーション | Btk阻害薬 |
JP2014520863A (ja) * | 2011-07-13 | 2014-08-25 | ファーマサイクリックス,インク. | Bruton型チロシンキナーゼの阻害剤 |
JP2014532768A (ja) * | 2011-11-08 | 2014-12-08 | インテリカイン, エルエルシー | 複数の医薬品を使用した治療レジメン |
JP2015518009A (ja) * | 2012-05-31 | 2015-06-25 | ファーマサイエンス・インコーポレイテッドPharmascience Inc. | プロテインキナーゼ阻害薬 |
JP2015519401A (ja) * | 2012-06-18 | 2015-07-09 | プリンシピア バイオファーマ インコーポレイテッド | 癌および自己免疫疾患の治療に有用な可逆性共有結合ピロロ−またはピラゾロピリミジン |
CN105732638A (zh) * | 2016-01-22 | 2016-07-06 | 成都倍特药业有限公司 | 一种具有螺环或桥环结构的布鲁顿酪氨酸激酶抑制剂及其制备方法 |
WO2017046604A1 (en) * | 2015-09-16 | 2017-03-23 | Redx Pharma Plc | Pyrazolopyrimidine derivatives as btk inhibitors for the treatment of cancer |
CN107827892A (zh) * | 2017-10-27 | 2018-03-23 | 上海应用技术大学 | 一种非受体酪氨酸激酶小分子抑制剂及其应用 |
WO2018089786A1 (en) * | 2016-11-11 | 2018-05-17 | Millennium Pharmaceuticals, Inc. | Atg7 inhibitors and the uses thereof |
WO2018189553A1 (en) * | 2017-04-13 | 2018-10-18 | Cancer Research Technology Limited | Compounds useful as ret inhibitors |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ517758A (en) * | 1999-09-17 | 2004-06-25 | Abbott Gmbh & Co | Pyrazolopyrimidines useful as therapeutic agents |
IL295053A (en) * | 2007-03-28 | 2022-09-01 | Pharmacyclics Llc | Broton tyrosine kinase inhibitors |
AU2009270856B2 (en) * | 2008-07-16 | 2013-07-25 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase for the treatment of solid tumors |
WO2013113097A1 (en) * | 2012-01-31 | 2013-08-08 | Beta Pharma Canada Inc. | Cyclic molecules as bruton's tyrosine kinase inhibitors |
AP2016009297A0 (en) * | 2014-02-03 | 2016-06-30 | Cadila Healthcare Ltd | Novel heterocyclic compounds |
CN105017256A (zh) * | 2014-04-29 | 2015-11-04 | 浙江导明医药科技有限公司 | 多氟化合物作为布鲁顿酪氨酸激酶抑制剂 |
TW201613919A (en) * | 2014-07-02 | 2016-04-16 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase |
TW201613926A (en) * | 2014-08-01 | 2016-04-16 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
AU2015296215A1 (en) * | 2014-08-01 | 2017-03-23 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
CN107344940B (zh) * | 2016-05-06 | 2020-04-21 | 广东东阳光药业有限公司 | Btk抑制剂及其用途 |
KR102327917B1 (ko) * | 2016-07-07 | 2021-11-17 | 주식회사 대웅제약 | 신규한 4-아미노피라졸로[3,4-d]피리미디닐아자바이사이클로 유도체 및 이를 포함하는 약학 조성물 |
-
2019
- 2019-01-18 CN CN201910049183.9A patent/CN111454268B/zh active Active
-
2020
- 2020-01-16 EA EA202191995A patent/EA202191995A1/ru unknown
- 2020-01-16 EP EP20741672.8A patent/EP3912980A4/en active Pending
- 2020-01-16 SG SG11202107886RA patent/SG11202107886RA/en unknown
- 2020-01-16 JP JP2021542229A patent/JP7436994B2/ja active Active
- 2020-01-16 CN CN202080009961.2A patent/CN113710671B/zh active Active
- 2020-01-16 US US17/423,815 patent/US20220081445A1/en active Pending
- 2020-01-16 CN CN202310355998.6A patent/CN116589465A/zh active Pending
- 2020-01-16 CA CA3129841A patent/CA3129841C/en active Active
- 2020-01-16 KR KR1020217025977A patent/KR20210135497A/ko not_active Application Discontinuation
- 2020-01-16 AU AU2020208128A patent/AU2020208128B2/en active Active
- 2020-01-16 BR BR112021014100-6A patent/BR112021014100A2/pt unknown
- 2020-01-16 MX MX2021008632A patent/MX2021008632A/es unknown
- 2020-01-16 WO PCT/CN2020/072551 patent/WO2020147798A1/zh unknown
-
2021
- 2021-07-18 IL IL284916A patent/IL284916A/en unknown
-
2023
- 2023-09-25 JP JP2023161762A patent/JP2023179562A/ja active Pending
Patent Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004531513A (ja) * | 2001-03-22 | 2004-10-14 | アボット ゲーエムベーハー ウント カンパニー カーゲー | 治療剤としてのピラゾールピリミジン |
JP2007520559A (ja) * | 2004-02-03 | 2007-07-26 | アボット・ラボラトリーズ | 治療薬としてのアミノベンゾオキサゾール類 |
JP2009520028A (ja) * | 2005-12-19 | 2009-05-21 | オーエスアイ・ファーマスーティカルズ・インコーポレーテッド | Igfr抑制剤および抗癌剤の併用 |
JP2010235628A (ja) * | 2006-09-22 | 2010-10-21 | Pharmacyclics Inc | ブルートンチロシンキナーゼ阻害剤 |
JP2013507448A (ja) * | 2009-10-12 | 2013-03-04 | ファーマサイクリクス,インコーポレイテッド | ブルトン型チロシンキナーゼの阻害剤 |
JP2014520863A (ja) * | 2011-07-13 | 2014-08-25 | ファーマサイクリックス,インク. | Bruton型チロシンキナーゼの阻害剤 |
JP2014520866A (ja) * | 2011-07-19 | 2014-08-25 | メルク・シャープ・アンド・ドーム・コーポレーション | Btk阻害薬 |
JP2014532768A (ja) * | 2011-11-08 | 2014-12-08 | インテリカイン, エルエルシー | 複数の医薬品を使用した治療レジメン |
JP2015518009A (ja) * | 2012-05-31 | 2015-06-25 | ファーマサイエンス・インコーポレイテッドPharmascience Inc. | プロテインキナーゼ阻害薬 |
JP2015519401A (ja) * | 2012-06-18 | 2015-07-09 | プリンシピア バイオファーマ インコーポレイテッド | 癌および自己免疫疾患の治療に有用な可逆性共有結合ピロロ−またはピラゾロピリミジン |
WO2017046604A1 (en) * | 2015-09-16 | 2017-03-23 | Redx Pharma Plc | Pyrazolopyrimidine derivatives as btk inhibitors for the treatment of cancer |
CN105732638A (zh) * | 2016-01-22 | 2016-07-06 | 成都倍特药业有限公司 | 一种具有螺环或桥环结构的布鲁顿酪氨酸激酶抑制剂及其制备方法 |
WO2018089786A1 (en) * | 2016-11-11 | 2018-05-17 | Millennium Pharmaceuticals, Inc. | Atg7 inhibitors and the uses thereof |
WO2018189553A1 (en) * | 2017-04-13 | 2018-10-18 | Cancer Research Technology Limited | Compounds useful as ret inhibitors |
CN107827892A (zh) * | 2017-10-27 | 2018-03-23 | 上海应用技术大学 | 一种非受体酪氨酸激酶小分子抑制剂及其应用 |
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AU2020208128A1 (en) | 2021-09-09 |
BR112021014100A2 (pt) | 2021-09-21 |
CN116589465A (zh) | 2023-08-15 |
CA3129841C (en) | 2023-09-26 |
CN113710671B (zh) | 2023-04-28 |
SG11202107886RA (en) | 2021-08-30 |
KR20210135497A (ko) | 2021-11-15 |
CN111454268A (zh) | 2020-07-28 |
JP2023179562A (ja) | 2023-12-19 |
MX2021008632A (es) | 2021-10-26 |
EP3912980A4 (en) | 2022-12-07 |
IL284916A (en) | 2021-09-30 |
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