CH5164840 | 1052645-73-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: CH5164840
• 英文别名: 4-amino-18,20-dimethyl-7-thia-3,5,11,15-tetraaza-tricyclo[15.3.1.1(2,6)]docosa-1(20),2(22),3,5,17(21),18-hexaene-10,16-dione；4-Amino-18,20-Dimethyl-7-Thia-3,5,11,15-Tetraazatricyclo[15.3.1.1(2,6)]docosa-1(20),2,4,6(22),17(21),18-Hexaene-10,16-Dione；4-amino-18,20-dimethyl-7-thia-3,5,11,15-tetrazatricyclo[15.3.1.12,6]docosa-1(21),2(22),3,5,17,19-hexaene-10,16-dione
• CAS: 1052645-73-4
• 化学式: C₁₉H₂₃N₅O₂S
• 分子量: 385.49
• InChiKey: OMFBVBRFVYLRQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-(2-amino-6-chloro-pyrimidin-4-yl)-2,4-dimethylbenzoic acid tert-butyl ester 在 1-羟基苯并三唑 、 caesium carbonate 、 苯甲醚 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 CH5164840
  参考文献：
  名称：

  Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors

  摘要：

  Macrocyclic compounds bearing a 2-amino-6-arylpyrimidine moiety were identified as potent heat shock protein 90 (Hsp90) inhibitors by modification of 2-amino-6-aryltriazine derivative (CH5015765). We employed a macrocyclic structure as a skeleton of new inhibitors to mimic the geldanamycin-Hsp90 interactions. Among the identified inhibitors. CH5164840 showed high binding affinity for N-terminal Hsp90 alpha (K-d = 0.52 nM) and strong anti-proliferative activity against human cancer cell lines (HCT116 IC50 = 0.15 mu M, NCI-N87 IC50 = 0.066 mu M). CH5164840 displayed high oral bioavailability in mice (F = 70.8%) and potent antitumor efficacy in a HCT116 human colorectal cancer xenograft model (tumor growth inhibition = 83%). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.100

文献信息

• TARGETED THERAPEUTICS
  申请人：Chimmanamada Dinesh U.

  公开号：US20140079636A1

  公开（公告）日：2014-03-20

  The present invention provides pharmacological compounds including an effector moiety conjugated to an binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

  本发明提供了药理化合物，包括将效应器基团偶联到结合基团上，以将效应器基团定向到感兴趣的生物靶点。同样，本发明提供了包括该化合物的组合物、试剂盒和方法（例如治疗、诊断和成像）。该化合物可以被描述为蛋白质相互作用的结合基团-药物偶联物（SDC-TRAP）化合物，包括蛋白质相互作用的结合基团和效应器基团。例如，在治疗癌症的某些实施方案中，SDC-TRAP可以包括Hsp90抑制剂与细胞毒素剂作为效应器基团的偶联物。
• Macrocyclic Compound
  申请人：Shimma Nobuo

  公开号：US20100056510A1

  公开（公告）日：2010-03-04

  The present invention provides a novel class of compounds that have the activity of inhibiting HSP90 enzyme and are useful as anti-cancer agents or such, and compounds that are useful as synthetic intermediates thereof. Specifically, the present invention provides compounds represented by the following formula (1), and pharmaceutically acceptable salts thereof: wherein X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , L 1 , L 2 , and L 3 are as defined in the specification.

  本发明提供了一种新型化合物类，具有抑制HSP90酶活性的特性，可用作抗癌剂或其他用途，以及用作其合成中间体的化合物。具体而言，本发明提供了以下式（1）所表示的化合物及其药学上可接受的盐：其中，X、R1、R2、R3、R4、R5、R6、R7、L1、L2和L3如规范中所定义。
• A BINDING MOIETY-DRUG CONJUGATE COMPRISING A HSP90 BINDING MOIETY AND A CYTOTOXIC EFFECTOR MOIETY
  申请人：Madrigal Pharmaceuticals, Inc.

  公开号：EP3466416A2

  公开（公告）日：2019-04-10

  The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

  本发明提供的药理化合物包括与结合基团共轭的效应分子，该结合基团可将效应分子导向感兴趣的生物靶标。同样，本发明还提供了包括这些化合物的组合物、试剂盒和方法（如治疗、诊断和成像）。这些化合物可被描述为蛋白质相互作用结合分子-药物共轭物（SDC-TRAP）化合物，其中包括蛋白质相互作用结合分子和效应分子。例如，在某些用于治疗癌症的实施方案中，SDC-TRAP 可包括与细胞毒剂共轭的 Hsp90 抑制剂作为效应分子。
• METHOD FOR PRODUCING CYCLIC ORGANIC COMPOUND
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP3623378A1

  公开（公告）日：2020-03-18

  An objective of the present invention is to provide methods of producing a cyclic organic compound using a continuous stirred tank reactor(s) (CSTR), the methods being capable of achieving excellent impurity-suppressing effects (quality improvement), reduction in reaction-tank size, continuous production, and such. The present inventors conducted studies on cyclization reactions using a CSTR(s), which had not been conventionally used for cyclization reactions for cyclic compounds. As a result, the inventors have found that the present methods can achieve excellent impurity-suppressing effects (quality improvement), reduction in reaction-tank size, continuous production, and such, as compared with conventional cyclization methods. Furthermore, the present inventors have also found that the above-mentioned improvement effects can efficiently be achieved even in the production of cyclic peptides and heterocyclic compounds by applying simulation methods that had been conventionally used mainly at the fine chemicals plant level to the cyclization reactions of the present invention, thereby experimentally predicting the reaction rate of a cyclization reaction, and setting the flow volume (residence time), the concentrations of precursor and cyclic organic compound, and the temperature for the cyclization reaction and such which affect these conditions, in the cyclization reaction using a CSTR(s).

  本发明的目的是提供使用连续搅拌罐反应器（CSTR）生产环状有机化合物的方法，这些方法能够达到极佳的抑制杂质效果（提高质量）、减小反应罐尺寸、连续生产等效果。本发明人对使用 CSTR 进行的环化反应进行了研究，CSTR 并未被常规用于环状化合物的环化反应。结果，本发明人发现，与传统的环化方法相比，本发明的方法可以达到极佳的抑制杂质效果（提高质量）、减小反应罐尺寸、实现连续生产等。此外，本发明人还发现，即使在环肽和杂环化合物的生产中，通过将传统上主要用于精细化工厂一级的模拟方法应用于本发明的环化反应，从而通过实验预测环化反应的反应速率，并在使用 CSTR 的环化反应中设定环化反应的流量（停留时间）、前体和环状有机化合物的浓度以及温度等影响这些条件的因素，也可以有效地实现上述改进效果。
• Targeted therapeutics
  申请人：Madrigal Pharmaceuticals, Inc.

  公开号：US10232049B2

  公开（公告）日：2019-03-19

  The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

  本发明提供的药理化合物包括与结合基团共轭的效应分子，该结合基团可将效应分子导向感兴趣的生物靶标。同样，本发明还提供了包括这些化合物的组合物、试剂盒和方法（如治疗、诊断和成像）。这些化合物可被描述为蛋白质相互作用结合分子-药物共轭物（SDC-TRAP）化合物，其中包括蛋白质相互作用结合分子和效应分子。例如，在某些用于治疗癌症的实施方案中，SDC-TRAP 可包括与细胞毒剂共轭的 Hsp90 抑制剂作为效应分子。