JP6594949B2 - サイクリン依存性キナーゼ7(cdk7)の阻害剤 - Google Patents
サイクリン依存性キナーゼ7(cdk7)の阻害剤 Download PDFInfo
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- JP6594949B2 JP6594949B2 JP2017503796A JP2017503796A JP6594949B2 JP 6594949 B2 JP6594949 B2 JP 6594949B2 JP 2017503796 A JP2017503796 A JP 2017503796A JP 2017503796 A JP2017503796 A JP 2017503796A JP 6594949 B2 JP6594949 B2 JP 6594949B2
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K31/5375—1,4-Oxazines, e.g. morpholine
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- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
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Description
本発明の実施形態において、例えば以下の項目が提供される。
(項目1)
構造式(Ic)を有する化合物であって、
式中、環A’’が、
から選択され、
R 7 、R 8 、及びR 10 の各々が独立して、水素及びメチルから選択され、
R 21a が、−Cl、−CN、−CF 3 、−CH 3 、及び−CH 2 CH 3 から選択され、
各R 12 が存在する場合、ハロであり、
oが、0、1、2、または3である、化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、立体異性体、もしくは同位体標識誘導体。
(項目2)
構造式(Ic’)を有し、
式中、環A’’、R 7 、R 8 、R 10 、R 21a 、R 12 、及びoが、項目1において定義された通りである、項目1に記載の化合物。
(項目3)
各R 12 が存在する場合、フルオロである、項目1または2に記載の化合物。
(項目4)
oが0である、項目1〜3のいずれか1項に記載の化合物。
(項目5)
以下に記述されている化合物:
のうちのいずれか1つから選択される、項目1に記載の化合物。
(項目6)
項目1〜5または16のいずれか1項に記載の化合物及び薬学的に許容される賦形剤を含む、薬学的組成物。
(項目7)
CDKの異常活性に関連する疾患または状態に罹患している対象を治療する際に使用するための項目6に記載の組成物。
(項目8)
前記対象がCDK7の異常活性に関連する疾患または状態に罹患している、項目7に記載の使用のための組成物。
(項目9)
癌、良性新生物、血管新生、炎症性疾患、自己炎症性疾患、自己免疫性疾患、または感染性疾患から選択される疾患または状態を治療する際に使用するための項目6に記載の組成物。
(項目10)
前記対象がヒトである、項目9に記載の使用のための組成物。
(項目11)
前記疾患が癌である、項目9〜10のいずれか1項に記載の使用のための組成物。
(項目12)
前記癌が、血液癌、黒色腫、骨癌、乳癌、脳腫瘍、または肺癌から選択される、項目11に記載の使用のための組成物。
(項目13)
前記癌が、慢性リンパ球性白血病(CLL)、急性リンパ芽球性白血病(ALL)、T細胞急性リンパ性白血病(T−ALL)、慢性骨髄性白血病(CML)、急性骨髄性白血病(AML)、リンパ腫、及び多発性骨髄腫から選択される血液癌である、項目12に記載の使用のための組成物。
(項目14)
前記癌が、骨肉腫、ユーイング肉腫、トリプルネガティブ乳癌(TNBC)、神経芽細胞腫、及び小細胞肺癌(SCLC)から選択される、項目12に記載の使用のための組成物。
(項目15)
前記組成物が、抗増殖剤、抗癌剤、免疫抑制剤、及び鎮痛剤から独立して選択される1つ以上のさらなる薬剤と併用して使用される、項目9〜14のいずれか1項に記載の使用のための組成物。
(項目16)
以下に記述されている化合物:
のうちのいずれか1つから選択される、化合物。
定義
他の定義
本発明の一態様では、構造式(Ic)の化合物であって、
R7、R8、及びR10の各々が独立して、水素及びメチルから選択され、
R21aが、−Cl、−CN、−CF3、−CH3、及び−CH2CH3から選択され、
各R12が存在する場合、ハロであり、
oが、0、1、2、または3である、化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、立体異性体、もしくは同位体標識誘導体が、提供される。
薬学的組成物、キット、及び投与
治療及び使用の方法
シクロヘキシル)カルバメート
Jurkat細胞。Jurkat細胞は、ヒトT細胞白血病から構築された細胞株である。本発明の代表的な化合物は、Jurkat細胞の増殖を阻害するそれらの能力について異なる濃度(10μM〜316pM、0.5対数連続希釈)で試験した。既知のCDK阻害剤であるフラボピリドール及びトリプトリドは、陽性対照として使用した。細胞は、RPMI 1640+10% FBS+1% Glutamax中で成長させた。細胞に、FBS(Life Technologies)及び100UmL−1ペニシリン、100μg・mL−1ストレプトマイシン(Invitrogen)を補給し、5% CO2の存在下で、加湿チャンバ内で37℃で培養した。増殖アッセイは、72時間の期間にわたって行った。CellTiter−Glo(登録商標)(Promega Corporation,Madison,WI USA)を用いて、製造業者の指示に従い、CellTiter−Glo(登録商標)キットに付属の試薬を利用して、化合物の抗増殖効果を評価した。この表では、「A」は、500nM未満のIC50を表し、「B」は、500nM〜5μMのIC50を表し、「C」は、5μM超のIC50を表す。
構造式(Ic)を有する化合物であって、
R7、R8、及びR10の各々が独立して、水素及びメチルから選択され、
R21aが、−Cl、−CN、−CF3、−CH3、及び−CH2CH3から選択され、
各R12が存在する場合、ハロであり、
oが、0、1、2、または3である、化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、立体異性体、もしくは同位体標識誘導体。
(項目2)
構造式(Ic’)を有し、
(項目3)
各R12が存在する場合、フルオロである、項目1または2に記載の化合物。
(項目4)
oが0である、項目1〜3のいずれか1項に記載の化合物。
(項目5)
化合物106、110、248、261、262、264、265、267、269、282、294、377、390、399、403、407、411、412、413のうちのいずれか1つから選択される、項目1に記載の化合物。
(項目6)
項目1〜5のいずれか1項に記載の化合物及び薬学的に許容される賦形剤を含む、薬学的組成物。
(項目7)
CDKの異常活性に関連する疾患または状態に罹患している対象を治療する際に使用するための項目6に記載の組成物。
(項目8)
前記対象がCDK7の異常活性に関連する疾患または状態に罹患している、項目7に記載の組成物。
(項目9)
前記疾患または状態が、癌、良性新生物、血管新生、炎症性疾患、自己炎症性疾患、自己免疫性疾患、または感染性疾患から選択される、項目7または8に記載の組成物。
(項目10)
前記対象がヒトである、項目7〜9のいずれか1項に記載の組成物。
(項目11)
前記疾患が癌である、項目7〜10のいずれか1項に記載の組成物。
(項目12)
前記癌が、血液癌、黒色腫、骨癌、乳癌、脳腫瘍、または肺癌から選択される、項目11に記載の組成物。
(項目13)
前記癌が、慢性リンパ球性白血病(CLL)、急性リンパ芽球性白血病(ALL)、T細胞急性リンパ性白血病(T−ALL)、慢性骨髄性白血病(CML)、急性骨髄性白血病(AML)、リンパ腫、及び多発性骨髄腫から選択される血液癌である、項目12に記載の組成物。
(項目14)
前記疾患が、骨肉腫、ユーイング肉腫、トリプルネガティブ乳癌(TNBC)、神経芽細胞腫、及び小細胞肺癌(SCLC)から選択される、項目12に記載の組成物。
(項目15)
前記組成物が、抗増殖剤、抗癌剤、免疫抑制剤、及び鎮痛剤から独立して選択される1つ以上のさらなる薬剤と併用して使用される、項目7〜14のいずれか1項に記載の組成物。
Claims (18)
- 構造式(Ic)を有する化合物であって、
式中、環A’’が、
から選択され、
R7、R8、及びR10の各々が独立して、水素及びメチルから選択され、
R21aが、−Cl、−CN、−CF3、−CH3、及び−CH2CH3から選択され、
各R12が存在する場合、ハロであり、
oが、0、1、2、または3である、化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、立体異性体、もしくは同位体標識誘導体。 - 構造式(Ic’)を有し、
式中、環A’’、R7、R8、R10、R21a、R12、及びoが、請求項1において定義された通りである、請求項1に記載の化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、立体異性体、もしくは同位体標識誘導体。 - 各R12が存在する場合、フルオロである、請求項1または2に記載の化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、立体異性体、もしくは同位体標識誘導体。
- oが0である、請求項1〜3のいずれか1項に記載の化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、立体異性体、もしくは同位体標識誘導体。
- 以下に記述されている化合物:
のうちのいずれか1つから選択される、請求項1に記載の化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、立体異性体、もしくは同位体標識誘導体。 - 環A’’が、
であり、
R 7 がメチルであり、
R 8 がHであり、
R 10 がHであり、
R 21a が−Clであり、
oが0である、請求項1に記載の化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、立体異性体、もしくは同位体標識誘導体。 - 請求項6に記載の薬学的に許容される塩。
- 以下に記述されている化合物:
のうちのいずれか1つから選択される、化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、立体異性体、もしくは同位体標識誘導体。 - 請求項1〜6および8のいずれか1項に記載の化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、立体異性体、もしくは同位体標識誘導体、あるいは請求項7に記載の薬学的に許容される塩及び薬学的に許容される賦形剤を含む、薬学的組成物。
- CDKの異常活性に関連する疾患または状態に罹患している対象を治療する際に使用するための請求項9に記載の薬学的組成物。
- 前記対象がCDK7の異常活性に関連する疾患または状態に罹患している、請求項10に記載の使用のための組成物。
- 対象における癌、良性新生物、血管新生、炎症性疾患、自己炎症性疾患、自己免疫性疾患、または感染性疾患から選択される疾患または状態を治療する際に使用するための請求項10に記載の組成物。
- 前記対象がヒトである、請求項12に記載の使用のための組成物。
- 前記疾患が癌である、請求項12〜13のいずれか1項に記載の使用のための組成物。
- 前記癌が、血液癌、黒色腫、骨癌、乳癌、脳腫瘍、神経芽細胞腫、または肺癌から選択される、請求項14に記載の使用のための組成物。
- 前記癌が、慢性リンパ球性白血病(CLL)、急性リンパ芽球性白血病(ALL)、T細胞急性リンパ性白血病(T−ALL)、慢性骨髄性白血病(CML)、急性骨髄性白血病(AML)、リンパ腫、及び多発性骨髄腫から選択される血液癌である、請求項15に記載の使用のための組成物。
- 前記癌が、骨肉腫、ユーイング肉腫、トリプルネガティブ乳癌(TNBC)、神経芽細胞腫、及び小細胞肺癌(SCLC)から選択される、請求項15に記載の使用のための組成物。
- 前記組成物が、抗増殖剤、抗癌剤、免疫抑制剤、及び鎮痛剤から独立して選択される1つ以上のさらなる薬剤と併用して使用される、請求項12〜17のいずれか1項に記載の使用のための組成物。
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US62/053,741 | 2014-09-22 | ||
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Families Citing this family (81)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2784807C (en) | 2009-12-29 | 2021-12-14 | Dana-Farber Cancer Institute, Inc. | Type ii raf kinase inhibitors |
EP2822935B1 (en) | 2011-11-17 | 2019-05-15 | Dana-Farber Cancer Institute, Inc. | Inhibitors of c-jun-n-terminal kinase (jnk) |
CA2927917C (en) | 2013-10-18 | 2022-08-09 | Syros Pharmaceuticals, Inc. | Heteroaromatic compounds useful for the treatment of proliferative diseases |
CN105849099B (zh) | 2013-10-18 | 2020-01-17 | 达纳-法伯癌症研究所股份有限公司 | 周期蛋白依赖性激酶7(cdk7)的多环抑制剂 |
AU2015240535A1 (en) | 2014-04-04 | 2016-10-20 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin-dependent kinase 7 (CDK7) |
US10246464B2 (en) | 2014-09-09 | 2019-04-02 | The Regents Of The University Of Michigan | Thienopyrimidine and thienopyridine compounds and methods of use thereof |
WO2016058544A1 (en) * | 2014-10-16 | 2016-04-21 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
KR102575327B1 (ko) | 2014-10-31 | 2023-09-07 | 유비이 가부시키가이샤 | 치환 디히드로피롤로피라졸 화합물 |
CA2972239A1 (en) | 2014-12-23 | 2016-06-30 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
WO2016144936A1 (en) | 2015-03-09 | 2016-09-15 | Bristol-Myers Squibb Company | Lactams as inhibitors of rock |
EP3273966B1 (en) | 2015-03-27 | 2023-05-03 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
WO2016197027A1 (en) | 2015-06-04 | 2016-12-08 | Kura Oncology, Inc. | Methods and compositions for inhibiting the interaction of menin with mll proteins |
TWI703150B (zh) | 2015-06-04 | 2020-09-01 | 美商庫拉腫瘤技術股份有限公司 | 用於抑制menin及mll蛋白之交互作用的方法及組合物 |
RU2765718C1 (ru) | 2015-06-15 | 2022-02-02 | Убе Индастриз, Лтд. | Замещенное производное дигидропирролопиразола |
CA2996978A1 (en) | 2015-09-09 | 2017-03-16 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
WO2017068412A1 (en) | 2015-10-21 | 2017-04-27 | Otsuka Pharmaceutical Co., Ltd. | Benzolactam compounds as protein kinase inhibitors |
JP6916796B2 (ja) | 2016-01-22 | 2021-08-11 | ヤンセン ファーマシューティカ エヌ.ベー. | Nik阻害剤としての新たな6員のヘテロ芳香族置換シアノインドリン誘導体 |
BR112018014675B1 (pt) | 2016-01-22 | 2023-12-19 | Janssen Pharmaceutica Nv | Derivados de cianoindolina substituída como inibidores de nik e composição farmacêutica que os compreende |
WO2017161002A1 (en) * | 2016-03-16 | 2017-09-21 | Kura Oncology, Inc. | Bridged bicyclic inhibitors of menin-mll and methods of use |
HUE061989T2 (hu) | 2016-03-16 | 2023-09-28 | Kura Oncology Inc | Szubsztituált tieno[2,3-D]pirimidin származékok mint menin-MLL inhibitorai és alkalmazási eljárások |
GB201604638D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
MX2018013413A (es) * | 2016-05-26 | 2019-06-06 | Zeno Royalties & Milestones Llc | Compuestos inhibidores de egfr. |
CA3026149A1 (en) | 2016-06-02 | 2017-12-07 | Cadent Therapeutics, Inc. | Potassium channel modulators |
CN109641882B (zh) | 2016-06-30 | 2022-10-28 | 杨森制药有限公司 | 作为nik抑制剂的杂芳族衍生物 |
AU2017289317B2 (en) | 2016-06-30 | 2021-04-01 | Janssen Pharmaceutica Nv | Cyanoindoline derivatives as NIK inhibitors |
SG11201900328WA (en) * | 2016-07-13 | 2019-02-27 | Jason Marineau | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
WO2018050631A1 (en) | 2016-09-13 | 2018-03-22 | Haplogen Gmbh | Antiviral compounds |
EP3544970B1 (en) * | 2016-11-22 | 2021-11-17 | Dana-Farber Cancer Institute, Inc. | Inhibitors of interleukin-1 receptor-associated kinases and uses thereof |
WO2018098361A1 (en) * | 2016-11-22 | 2018-05-31 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 12 (cdk12) and uses thereof |
EA039109B1 (ru) * | 2016-12-07 | 2021-12-06 | Кура Онколоджи, Инк. | Мостиковые бициклические ингибиторы взаимодействия менин-mll и способы применения |
EP4306166A2 (en) * | 2016-12-23 | 2024-01-17 | Aquinnah Pharmaceuticals Inc. | Compounds, compositions and methods of use |
TWI751271B (zh) | 2017-01-23 | 2022-01-01 | 美商凱登製藥公司 | 鉀離子通道調節子 |
TWI810172B (zh) * | 2017-01-26 | 2023-08-01 | 南韓商韓美藥品股份有限公司 | 嘧啶化合物及包括其的藥學組成物 |
CN110418789B (zh) * | 2017-02-01 | 2022-03-25 | 常州千红生化制药股份有限公司 | 作为治疗剂的N-环烷基/杂环烷基-4-(咪唑并[1,2-a]吡啶)嘧啶-2-胺的衍生物 |
JP2020514388A (ja) | 2017-03-24 | 2020-05-21 | クラ オンコロジー,インク. | 血液悪性腫瘍およびユーイング肉腫を処置するための方法 |
TW201841640A (zh) * | 2017-04-07 | 2018-12-01 | 美商錫羅斯製藥公司 | 週期素依賴型激酶7(cdk7)抑制劑之組合物 |
GB201706327D0 (en) | 2017-04-20 | 2017-06-07 | Otsuka Pharma Co Ltd | A pharmaceutical compound |
EP3630079A4 (en) | 2017-05-31 | 2021-02-24 | The Children's Medical Center Corporation | TARGETING LYSINE DEMETHYLASE (KDMS) AS A THERAPEUTIC STRATEGY FOR DIFFUSED LARGE B-CELL LYMPHOMA |
US11542248B2 (en) | 2017-06-08 | 2023-01-03 | Kura Oncology, Inc. | Methods and compositions for inhibiting the interaction of menin with MLL proteins |
EP3638242A4 (en) * | 2017-06-12 | 2021-10-27 | Syros Pharmaceuticals, Inc. | COMPOSITIONS AND METHODS OF TREATMENT OF CANCERS WITH COVALENT CYCLINE-DEPENDENT KINASE 7 INHIBITORS (CDK7) |
CN107474046B (zh) * | 2017-07-07 | 2019-08-27 | 南方医科大学 | 一类吡啶并三氮唑化合物及其制备方法和应用 |
US10913983B2 (en) | 2017-07-18 | 2021-02-09 | University Of South Carolina | Sensitivity markers and uses for CDK7 inhibitors in breast cancers |
SG11202000532SA (en) | 2017-08-09 | 2020-02-27 | Denali Therapeutics Inc | Compounds, compositions and methods |
TW201920170A (zh) | 2017-09-20 | 2019-06-01 | 美商庫拉腫瘤技術股份有限公司 | 經取代之menin-mll 抑制劑及使用方法 |
WO2019078968A2 (en) * | 2017-10-18 | 2019-04-25 | Angex Pharmaceutical, Inc. | CYCLIC COMPOUNDS AS IMMUNOMODULATORS |
MX2020004557A (es) | 2017-11-02 | 2020-10-05 | Calico Life Sciences Llc | Moduladores de la vía de estrés integrada. |
AU2019209470A1 (en) | 2018-01-16 | 2020-08-13 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin-dependent kinase 7 (CDK7) |
US11918592B2 (en) | 2018-01-16 | 2024-03-05 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin dependent kinase 7 (CDK7) |
CN111247137A (zh) * | 2018-02-13 | 2020-06-05 | 恩瑞生物医药科技(上海)有限公司 | 一种嘧啶类化合物、其制备方法及其医药用途 |
SG11202009992VA (en) | 2018-04-26 | 2020-11-27 | Pfizer | 2-amino-pyridine or 2-amino-pyrimidine derivatives as cyclin dependent kinase inhibitors |
AU2019203034B1 (en) | 2018-07-25 | 2019-09-26 | Hanmi Pharm. Co., Ltd. | Pyrimidine compounds and pharmaceutical compositions for preventing or treating cancers including the same |
KR101954370B1 (ko) * | 2018-07-25 | 2019-03-05 | 한미약품 주식회사 | 피리미딘 화합물 및 이를 포함하는 암의 예방 또는 치료용 약학 조성물 |
BR112021004999A2 (pt) | 2018-09-17 | 2021-06-08 | Yungjin Pharm. Co., Ltd. | composto e método de inibição de cdk7 em um sujeito |
TWI767148B (zh) | 2018-10-10 | 2022-06-11 | 美商弗瑪治療公司 | 抑制脂肪酸合成酶(fasn) |
US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
TWI771621B (zh) | 2018-10-11 | 2022-07-21 | 美商嘉來克生命科學有限責任公司 | 整合應激路徑之前藥調節劑 |
US11993586B2 (en) | 2018-10-22 | 2024-05-28 | Novartis Ag | Crystalline forms of potassium channel modulators |
CR20210287A (es) * | 2018-11-01 | 2022-02-15 | Syros Pharmaceuticals Inc | Inhibidores de cinasa 7 dependiente de ciclina (cdk7) |
WO2020100944A1 (ja) | 2018-11-14 | 2020-05-22 | 宇部興産株式会社 | ジヒドロピロロピラゾール誘導体 |
CA3121202A1 (en) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
JP7417540B2 (ja) | 2018-12-06 | 2024-01-18 | 第一三共株式会社 | シクロアルカン-1,3-ジアミン誘導体 |
PE20212023A1 (es) | 2019-02-13 | 2021-10-18 | Denali Therapeutics Inc | Compuestos, composiciones y metodos |
WO2020168197A1 (en) | 2019-02-15 | 2020-08-20 | Incyte Corporation | Pyrrolo[2,3-d]pyrimidinone compounds as cdk2 inhibitors |
US11472791B2 (en) | 2019-03-05 | 2022-10-18 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as CDK2 inhibitors |
CN109824545B (zh) * | 2019-03-14 | 2021-02-26 | 泰州精英化成医药科技有限公司 | 一种反式-4-N-Boc-氨基环己烷羧酸的制备方法 |
WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
WO2020219650A1 (en) * | 2019-04-23 | 2020-10-29 | Dana-Farber Cancer Institute, Inc. | Degraders of cyclin-dependent kinase 12 (cdk12) and uses thereof |
US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
US11440914B2 (en) | 2019-05-01 | 2022-09-13 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
CR20220066A (es) | 2019-08-14 | 2022-11-28 | Incyte Corp | Compuestos de imidazolil pirimidinilamina como inhibidores de cdk2 |
WO2021072232A1 (en) | 2019-10-11 | 2021-04-15 | Incyte Corporation | Bicyclic amines as cdk2 inhibitors |
EP4241773A1 (en) * | 2020-11-05 | 2023-09-13 | Hanmi Pharm. Co., Ltd. | Pharmaceutical composition for treating leukemia comprising flt3 inhibitor |
CN112716957B (zh) * | 2020-12-28 | 2022-10-14 | 复旦大学附属肿瘤医院 | Cdk7靶向抑制剂在制备治疗car-t治疗引起的细胞因子释放综合征药物中的用途 |
CN112656798B (zh) * | 2020-12-28 | 2023-03-07 | 复旦大学附属肿瘤医院 | Cdk7靶向抑制剂在制备治疗细胞因子释放综合征药物中的应用 |
US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
WO2023091726A1 (en) * | 2021-11-18 | 2023-05-25 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin‑dependent kinase 12 (cdk12) |
US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
TW202340211A (zh) * | 2021-12-22 | 2023-10-16 | 香港商英矽智能科技知識產權有限公司 | 嘧啶雜環化合物、其製法與醫藥上的用途 |
CN114380806B (zh) * | 2022-03-24 | 2022-06-10 | 中国药科大学 | 2-氨基-4-吲哚基嘧啶类化合物及其制备方法与应用 |
WO2023227125A1 (zh) * | 2022-05-26 | 2023-11-30 | 杭州德睿智药科技有限公司 | 作为CDKs抑制剂的新型并杂环类新化合物及其应用 |
WO2024096708A1 (en) * | 2022-11-04 | 2024-05-10 | Hanmi Pharm. Co., Ltd. | Novel crystalline form of a pyrimidine compound and pharmaceutical compositions comprising the same and methods of use thereof |
Family Cites Families (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5571813A (en) | 1993-06-10 | 1996-11-05 | Beiersdorf-Lilly Gmbh | Fused pyrimidine compounds and their use as pharmaceuticals |
GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
WO2001072745A1 (en) | 2000-03-29 | 2001-10-04 | Cyclacel Limited | 2-substituted 4-heteroaryl-pyrimidines and their use in the treatmetn of proliferative disorders |
EP1373257B9 (en) | 2001-03-29 | 2008-10-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
EP1392662B1 (de) * | 2001-05-29 | 2009-01-07 | Bayer Schering Pharma Aktiengesellschaft | Cdk inhibitorische pyrimidine, deren herstellung und verwendung als arzneimittel |
PL367676A1 (en) | 2001-05-29 | 2005-03-07 | Kyoto Pharmaceutical Industries, Ltd. | Novel heterocyclic derivatives and medicinal use thereof |
JP2003050442A (ja) | 2001-06-01 | 2003-02-21 | Fuji Photo Film Co Ltd | 記録材料 |
DE60214703T2 (de) | 2001-06-01 | 2007-09-13 | Vertex Pharmaceuticals Inc., Cambridge | Thiazolverbindungen, die sich als inhibitoren von proteinkinasen eignen |
DE60232510D1 (de) | 2001-06-15 | 2009-07-16 | Vertex Pharma | 5-(2-aminopyrimidin-4-yl)benzisoxazole als proteinkinasehemmer |
US7115617B2 (en) | 2001-08-22 | 2006-10-03 | Amgen Inc. | Amino-substituted pyrimidinyl derivatives and methods of use |
US6939874B2 (en) | 2001-08-22 | 2005-09-06 | Amgen Inc. | Substituted pyrimidinyl derivatives and methods of use |
ES2314106T3 (es) * | 2001-10-17 | 2009-03-16 | BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG | Derivados de pirimidina, agentes farmaceuticos que contiene dichos compuestos, uso y metodo para su obtencion. |
CA2487679A1 (en) * | 2002-05-30 | 2003-12-11 | Vertex Pharmaceuticals Incorporated | Inhibitors of jak and cdk2 protein kinases |
AU2003247959B2 (en) | 2002-07-09 | 2010-07-29 | Vertex Pharmaceuticals Incorporated | Imidazoles, oxazoles and thiazoles with protein kinase inhibiting activities |
KR101088922B1 (ko) | 2002-09-04 | 2011-12-01 | 파마코페이아, 엘엘씨. | 사이클린 의존성 키나제 억제제로서의 피라졸로피리미딘 |
JP4564485B2 (ja) | 2003-02-28 | 2010-10-20 | 帝人ファーマ株式会社 | ピラゾロ[1,5−a]ピリミジン誘導体 |
GB0305559D0 (en) | 2003-03-11 | 2003-04-16 | Teijin Ltd | Compounds |
WO2004087699A2 (en) | 2003-03-25 | 2004-10-14 | Vertex Pharmaceuticals Incorporated | Thiazoles useful as inhibitors of protein kinases |
GB0411791D0 (en) * | 2004-05-26 | 2004-06-30 | Cyclacel Ltd | Compounds |
JP2008507541A (ja) | 2004-07-23 | 2008-03-13 | ロイヤルティ,スーザン・マリー | ペプチダーゼ阻害剤 |
US7855205B2 (en) * | 2004-10-29 | 2010-12-21 | Janssen Pharmaceutica Nv | Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders |
GB0520955D0 (en) | 2005-10-14 | 2005-11-23 | Cyclacel Ltd | Compound |
US7790770B2 (en) | 2005-11-23 | 2010-09-07 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
WO2007129195A2 (en) * | 2006-05-04 | 2007-11-15 | Pfizer Products Inc. | 4-pyrimidine-5-amino-pyrazole compounds |
EP2029578A1 (en) | 2006-05-26 | 2009-03-04 | AstraZeneca AB | 2-carbocycloamino-4-imidaz0lylpyrimidines as agents for the inhbition of cell proliferation |
ATE543498T1 (de) | 2006-09-08 | 2012-02-15 | Hoffmann La Roche | Benzotriazol kinasemodulatoren |
JP5179509B2 (ja) | 2006-12-08 | 2013-04-10 | エフ.ホフマン−ラ ロシュ アーゲー | 置換ピリミジン類及びjnkモジュレーターとしてのこれらの使用 |
EP2152079A4 (en) * | 2007-06-04 | 2011-03-09 | Avila Therapeutics Inc | HETEROCYCLIC COMPOUNDS AND USES THEREOF |
JP2010529140A (ja) | 2007-06-05 | 2010-08-26 | エモリー・ユニバーシテイ | サイクリン依存性キナーゼの選択的阻害剤 |
US20090054392A1 (en) | 2007-08-20 | 2009-02-26 | Wyeth | Naphthylpyrimidine, naphthylpyrazine and naphthylpyridazine analogs and their use as agonists of the wnt-beta-catenin cellular messaging system |
CN101723936B (zh) | 2008-10-27 | 2014-01-15 | 上海睿星基因技术有限公司 | 激酶抑制剂及其在药学中的用途 |
EP2397479A4 (en) | 2009-02-12 | 2012-08-01 | Astellas Pharma Inc | HETERO RING DERIVATIVE |
SG176722A1 (en) | 2009-06-17 | 2012-01-30 | Vertex Pharma | Inhibitors of influenza viruses replication |
WO2011018417A1 (en) * | 2009-08-10 | 2011-02-17 | F. Hoffmann-La Roche Ag | Inhibitors of jnk |
US9556426B2 (en) * | 2009-09-16 | 2017-01-31 | Celgene Avilomics Research, Inc. | Protein kinase conjugates and inhibitors |
EP2822935B1 (en) | 2011-11-17 | 2019-05-15 | Dana-Farber Cancer Institute, Inc. | Inhibitors of c-jun-n-terminal kinase (jnk) |
EP2634189A1 (en) | 2012-03-01 | 2013-09-04 | Lead Discovery Center GmbH | Pyrazolo-triazine derivatives as selective cyclin-dependent kinase inhibitors |
EP2634190A1 (en) | 2012-03-01 | 2013-09-04 | Lead Discovery Center GmbH | Pyrazolo-triazine derivatives as selective cyclin-dependent kinase inhinitors |
EP2909194A1 (en) * | 2012-10-18 | 2015-08-26 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
US20140259005A1 (en) | 2013-03-08 | 2014-09-11 | Air Computing, Inc. | Systems and methods for managing files in a cloud-based computing environment |
AU2014337067B2 (en) | 2013-10-18 | 2019-01-24 | Syros Pharmaceuticals, Inc. | Heteroaromatic compounds useful for the treatment of proliferative diseases |
CA2927917C (en) | 2013-10-18 | 2022-08-09 | Syros Pharmaceuticals, Inc. | Heteroaromatic compounds useful for the treatment of proliferative diseases |
CN105849099B (zh) * | 2013-10-18 | 2020-01-17 | 达纳-法伯癌症研究所股份有限公司 | 周期蛋白依赖性激酶7(cdk7)的多环抑制剂 |
AU2015240535A1 (en) * | 2014-04-04 | 2016-10-20 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin-dependent kinase 7 (CDK7) |
WO2015154022A1 (en) | 2014-04-05 | 2015-10-08 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
WO2016058544A1 (en) | 2014-10-16 | 2016-04-21 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
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