3-[(3-氯苯氧基)甲基]-1-(四氢-2H-吡喃-4-基)-1H-吡唑并[3,4-D]嘧啶-4-胺 | 1188296-52-7

• 物质功能分类: 生物 - 细胞培养 - 添加剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 中文名称: 3-[(3-氯苯氧基)甲基]-1-(四氢-2H-吡喃-4-基)-1H-吡唑并[3,4-D]嘧啶-4-胺
• 英文名称: 3-[(3-Chlorophenoxy)methyl]-1-(Tetrahydro-2h-Pyran-4-Yl)-1h-Pyrazolo[3,4-D]pyrimidin-4-Amine
• 英文别名: 3-[(3-chlorophenoxy)methyl]-1-(oxan-4-yl)pyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 1188296-52-7
• 化学式: C₁₇H₁₈ClN₅O₂
• 分子量: 359.8
• InChiKey: AUMDBEHGJRZSOO-UHFFFAOYSA-N

物化性质

• 沸点：
  592.9±50.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：25mg/mL； DMF:PBS(pH 7.2)(1:1)：0.5 mg/ml； DMSO：10mg/mL；乙醇：1mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  88.1
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

PF 4800567 是一种新型有效抑制剂，对 casein kinase 1 epsilon (IC50 = 32 nM) 具有较高的选择性，其选择性是 casein kinase 1 delta (IC50 = 711 nM) 的近 20 倍。

靶点

Target	Value
Casein kinase 1 epsilon (Cell-free assay)	32 nM
Casein kinase 1 delta	711 nM

体外研究

PF-4800567 是一种对 casein kinase 1 ε (CK1ε) 具有高选择性的强效抑制剂，IC50 值为 32 nM。相比 CK1δ（IC50 = 711 nM），其选择性超过 20 倍。在全细胞中，PF-4800567 对 CK1ε 和 CK1δ 的 IC50 值分别为 2.65 μM 和 20.38 μM。该化合物以 0.01 至 10 μM 浓度阻断了由 CK1ε 引起的 PER3 核定位，并在 1 μM 浓度下抑制了 PER2 的降解，但对生物钟的影响较小。

体内研究

PF-4800567 (100 mg/kg, s.c.) 在小鼠中的吸收和分布迅速，在血浆和脑组织中都能被快速检测到。

用途

PF 4800567 是一种选择性 casein kinase 抑制剂，对 CK1ε 的抑制效力比 CK1δ 高出 22 倍（IC50 值分别为 32 nM 和 711 nM），且为 ATP 竞争性抑制。该化合物表现出 minimal 对生物钟的影响。

文献信息

• [EN] A CASEIN KINASE 1 DELTA INHIBITOR<br/>[FR] INHIBITEUR DE LA CASÉINE KINASE 1 DELTA
  申请人：ELECTROPHORETICS LTD

  公开号：WO2016180981A1

  公开（公告）日：2016-11-17

  The present invention provides 2-Methyl-amino-3-[(4-fluorophenyl) carbonyl] indolizine-1-carboxamide of formula (I) or a pharmaceutically acceptable salt thereof and its therapeutic uses in the treatment of neurodegenerative disorders, in particular tauopathies and most preferably in the treatment of Alzheimer's disease.

  本发明提供了式(I)的2-甲基氨基-3-[(4-氟苯基)羰基]吲哚啉-1-羧酰胺或其药学上可接受的盐，以及其在治疗神经退行性疾病，特别是tau蛋白病和更好地在治疗阿尔茨海默病中的治疗用途。
• [EN] COMPOUNDS AND METHODS USEFUL FOR TREATING OR PREVENTING CANCERS<br/>[FR] COMPOSÉS ET MÉTHODES UTILES POUR LE TRAITEMENT OU LA PRÉVENTION DE CANCERS
  申请人：CORSELLO STEVEN M

  公开号：WO2018183936A1

  公开（公告）日：2018-10-04

  The present invention includes CSNK1A1 inhibitors that are useful in treating or preventing a cancer in a subject. In certain embodiments, the cancer comprises a hematological cancer, such as but not limited to acute myeloid leukemia (AML) and/or MDS (myelodysplastic syndrome, including 5q-MDS). In other embodiments, the cancer comprises colon cancer.

  本发明涉及CSNK1A1抑制剂，可用于治疗或预防受试者中的癌症。在某些实施例中，癌症包括血液系统癌症，如但不限于急性髓系白血病（AML）和/或MDS（髓增生异常综合征，包括5q-MDS）。在其他实施例中，癌症包括结肠癌。
• CASEIN KINASE 1epsilon INHIBITOR, PHARMACEUTICAL COMPOSITION AND APPLICATION THEREOF
  申请人：Hangzhou Healzen Therapeutics Co., Ltd.

  公开号：EP3964512A1

  公开（公告）日：2022-03-09

  Disclosed in the present invention is a novel substituted pyrazolopyrimidine compound that inhibits the activity of casein kinase 1ε (CK1ε) and a stereoisomer or stereoisomer mixture thereof, or a pharmaceutically acceptable salt or solvate thereof, and an application thereof in preparation of drugs for treating diseases, disorders or conditions that benefit from the inhibition of the activity of the casein kinase 1ε (CK1ε). The compound of the present invention has an inhibitory activity on CK1ε kinase, OCI-LY10 cells and Karpas299 cells, shows good anti-tumor activity in an OCI-LY10 subcutaneous xenogeneic model and shows excellent synergistic anti-tumor activity in combination with BTK inhibitors. The compound of the present invention has good pharmacokinetics properties and may be used alone or in combination with other drugs to treat diseases, disorders or conditions that benefit from the inhibition of the activity of the casein kinase 1ε, the diseases, disorders or conditions comprising tumors, autoimmune diseases, etc.

  本发明公开了一种抑制酪蛋白激酶1ε（CK1ε）活性的新型取代吡唑嘧啶化合物及其立体异构体或立体异构体混合物，或其药学上可接受的盐或溶液，以及其在制备用于治疗从抑制酪蛋白激酶1ε（CK1ε）活性中获益的疾病、失调或病症的药物中的应用。本发明化合物对 CK1ε 激酶、OCI-LY10 细胞和 Karpas299 细胞具有抑制活性，在 OCI-LY10 皮下异种模型中显示出良好的抗肿瘤活性，与 BTK 抑制剂联合使用显示出优异的协同抗肿瘤活性。本发明的化合物具有良好的药代动力学特性，可单独使用或与其他药物联合使用，治疗因抑制酪蛋白激酶 1ε 的活性而获益的疾病、失调或病症，这些疾病、失调或病症包括肿瘤、自身免疫性疾病等。
• Methods for identifying and using inhibitors of casein kinase 1 epsilon isoform for inhibiting the growth and/or proliferation of MYC-driven tumor cells
  申请人：Fred Hutchinson Cancer Research Center

  公开号：US10188630B2

  公开（公告）日：2019-01-29

  In one aspect, the invention provides a method for inhibiting the growth and/or proliferation of a myc-driven tumor cell comprising the step of contacting the tumor cells with a CSNK1ε inhibitor. In another aspect, the invention provides a method of treating a subject suffering from a tumor comprising myc-driven tumor cells, comprising administering to the subject an amount of a composition comprising a CSNK1ε inhibitor effective to inhibit the growth and/or proliferation of the tumor cells.

  一方面，本发明提供了一种抑制myc驱动的肿瘤细胞生长和/或增殖的方法，包括使肿瘤细胞与CSNK1ε抑制剂接触的步骤。在另一方面，本发明提供了一种治疗由myc驱动的肿瘤细胞组成的肿瘤患者的方法，该方法包括向该患者施用一定量的包含CSNK1ε抑制剂的组合物，该组合物能有效抑制肿瘤细胞的生长和/或增殖。
• Treatment of respiratory diseases
  申请人：The University of Melbourne

  公开号：US10722513B2

  公开（公告）日：2020-07-28

  The present invention relates to compositions, methods and kits for the treatment of respiratory disease. In particular, the compositions, methods and kits are particularly useful, but not limited to, the treatment or prevention of exacerbations of asthma and chronic obstructive pulmonary disease. The present invention provides a method of treating or preventing a respiratory disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of casein kinase 1, thereby treating or preventing a respiratory disease in a subject. The present invention also provides a method of treating or preventing a respiratory disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of ALK5, thereby treating or preventing a respiratory disease in a subject, wherein the inhibitor is administered directly to the airway and/or lungs. The present invention also provides a method of treating or preventing a condition of the airway or lung involving fibrosis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of casein kinase 1 or an inhibitor of ALK5, thereby treating or preventing a condition of the airway or lung involving fibrosis in a subject.

  本发明涉及治疗呼吸系统疾病的组合物、方法和试剂盒。特别是，本发明的组合物、方法和试剂盒特别有用，但不限于治疗或预防哮喘和慢性阻塞性肺病的恶化。本发明提供了一种治疗或预防有需要的受试者呼吸系统疾病的方法，该方法包括向受试者施用治疗有效量的酪蛋白激酶1抑制剂，从而治疗或预防受试者的呼吸系统疾病。本发明还提供了一种治疗或预防有需要的受试者的呼吸系统疾病的方法，该方法包括向受试者施用治疗有效量的ALK5抑制剂，从而治疗或预防受试者的呼吸系统疾病，其中抑制剂直接施用至气道和/或肺部。本发明还提供了一种治疗或预防有需要的受试者气道或肺部涉及纤维化的病症的方法，该方法包括向受试者施用治疗有效量的酪蛋白激酶1抑制剂或ALK5抑制剂，从而治疗或预防受试者气道或肺部涉及纤维化的病症。