8-chloro-2-(morpholin-4-ylmethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one | 1108169-08-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 8-chloro-2-(morpholin-4-ylmethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one
• 英文别名: Benzothienopyrimidinone deriv., 6d；8-chloro-2-(morpholin-4-ylmethyl)-3H-[1]benzothiolo[3,2-d]pyrimidin-4-one
• CAS: 1108169-08-9
• 化学式: C₁₅H₁₄ClN₃O₂S
• 分子量: 335.814
• InChiKey: AZJVHIQQEYWSIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  吗啉 、 8-chloro-2-(chloromethyl)-3H-[1]benzothiolo[3,2-d]pyrimidin-4-one 以 N,N-二甲基甲酰胺 为溶剂， 生成 8-chloro-2-(morpholin-4-ylmethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one
  参考文献：
  名称：

  Discovery of 3H-Benzo[4,5]thieno[3,2-d]pyrimidin-4-ones as Potent, Highly Selective, and Orally Bioavailable Inhibitors of the Human Protooncogene Proviral Insertion Site in Moloney Murine Leukemia Virus (PIM) Kinases

  摘要：

  Pim-1, Pim-2, and Pim-3 are a family of serine/threonine kinases which have been Found to be overexpressed in a variety of hematopoietic malignancies and solid tumors. Benzothienopyrimidinones were discovered as a novel class of Pim inhibitors that potently inhibit all three Pim kinases with subnanomolar to low single-digit nanomolar K-i values and exhibit excellent selectivity against a panel of diverse kinases. Protein crystal structures of the bound Pim-1 complexes of benzothienopyrimidinones 3b (PDB code 3JYA), 6e (PDB code 3JYO), and 12b (PDB code 3JXW) were determined and used to guide SAR studies. Multiple compounds exhibited potent antiproliferative activity in K562 and MV4-11 cells with submicromolar EC50 values. For example, compound 14j inhibited the growth of K562 cells with an EC50 value of 1.7 mu M and showed K-i values of 2, 3, and 0.5 nM against Pim-1, Pim-2, and Pim-3, respectively. These novel Pim kinase inhibitors efficiently interrupted the phosphorylation of Bad in both K562 and LnCaP-Bad cell lines, indicating that their potent biological activities are mechanism-based. The pharmacokinetics of 14j was studied in CD-1 mice and shown to exhibit bioavailability of 76% after oral dosing. ADME profiling of 14j suggested a long half-life in both human and mouse liver microsomes, good permeability, modest protein bin-ling, and no CYP inhibition below 20 mu M concentration.

  DOI：

  10.1021/jm900943h

文献信息

• PIM KINASE INHIBITORS AS CANCER CHEMOTHERAPEUTICS
  申请人：Wang Le

  公开号：US20090030196A1

  公开（公告）日：2009-01-29

  Inhibitors of Pim kinases, ways to make them and methods of treating patients using them are disclosed.

  本发明揭示了抑制Pim激酶的抑制剂、制备方法以及使用它们治疗患者的方法。
• Treatment and after-treatment of metal with polyphenol compounds
  申请人：HENKEL CORPORATION (a Delaware corp.)

  公开号：EP0319016A2

  公开（公告）日：1989-06-07

  A metal treatment solution comprising an effective amount of a soluble or dispersible compound which is a derivative of a polyphenol. A composition for treatment and after treatment of metal with polyphenol compounds is provided. The present invention includes novel derivatives of polyphenol compounds which are useful in surface treatment solutions or dispersions. A method for using these solutions or dispersions is also provided. The molecular weight of the polyphenols used to form the derivatives of the present invention are in the range of from about 360 to 30,000 or greater. The resulting derivatives of the present invention typically have a molecular weight of up to about 2,000,000 with molecular weights within the range of about 700 to about 70,000 being preferred.

  一种金属处理液，含有有效量的可溶性或分散性化合物，它是一种多酚的衍生物。本发明提供了一种用多酚化合物处理金属和金属处理后的组合物。本发明包括可用于表面处理溶液或分散体的新型多酚化合物衍生物。本发明还提供了使用这些溶液或分散体的方法。用于形成本发明衍生物的多酚的分子量在约 360 到 30000 或更大的范围内。由此产生的本发明衍生物的分子量通常高达约 2,000,000 ，分子量在约 700 至约 70,000 范围内为优选。
• Treatment and after-treatment of metal with carbohydrate-modified polyphenol compounds
  申请人：HENKEL CORPORATION (a Delaware corp.)

  公开号：EP0319017A2

  公开（公告）日：1989-06-07

  A metal treatment solution comprising an effective amount of a soluble or dispersible compound which is a derivative of a polyphenol. Novel derivatives of polyphenol compounds useful in the treatment of the surface of metal articles is provided. Novel surface treatment solutions or dispersions, and methods for using these solutions is provided. Carbohydrate-modified polyphenol compounds are utilized in the present invention. The molecular weight of the polyphenols used in the preparation of derivatives of the present invention are in the range of about 360 to about 30,000 or greater. The resulting derivatives will typically have a molecular weight of up to about 2,000,000 with molecular weights within the range of about 700 to about 70,000 being preferred.

  一种金属处理溶液，含有有效量的可溶性或分散性化合物，它是一种多酚的衍生物。提供了可用于金属制品表面处理的新型多酚化合物衍生物。提供了新型表面处理溶液或分散体，以及使用这些溶液的方法。本发明采用了碳水化合物改性的多酚化合物。用于制备本发明衍生物的多酚的分子量在约 360 至约 30,000 或更大的范围内。所得衍生物的分子量通常高达约 2,000,000 ，分子量在约 700 至约 70,000 范围内为优选。
• Increasing and maintaining the hydrophilic nature of an oxidized plastic surface
  申请人：Held D. Theodore

  公开号：US20060121284A1

  公开（公告）日：2006-06-08

  In at least one embodiment, the present invention relates to a increasing the hydrophilicity of an organic surface. One method in accordance with the present invention includes oxidizing at least a portion of the organic surface to form an oxidized surface portion, and treating the oxidized surfaces portion with an aqueous treatment solution comprising water-soluble and/or water-dispersible polyphenol resin. In at least another embodiment, the present invention relates to preventing the formation of coating defects in polymeric coated surfaces. In at least one embodiment, the present invention relates to increasing paint, ink, and adhesive adhesion.

  在至少一个实施方案中，本发明涉及增加有机表面亲水性的方法。根据本发明的一种方法包括氧化至少一部分有机表面以形成氧化表面部分，并用包含水溶性和/或水分散性多酚树脂的水处理溶液处理氧化表面部分。至少在另一个实施方案中，本发明涉及防止聚合物涂层表面形成涂层缺陷。在至少一个实施方案中，本发明涉及提高涂料、油墨和粘合剂的附着力。
• RINSE AID FOR PLASTIC AND PAINTED SURFACES
  申请人：HENKEL CORPORATION

  公开号：EP0507871A1

  公开（公告）日：1992-10-14