2-(2-(2-(2-(5-(4-acrylamido-6-aminopyrimidin-2-ylthio)-6-methoxy-2-(4-methylpiperazin-1-yl)pyrimidin-4-yloxy)ethoxy)ethoxy)ethoxy)ethyl 5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoate | 1268273-42-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: 2-(2-(2-(2-(5-(4-acrylamido-6-aminopyrimidin-2-ylthio)-6-methoxy-2-(4-methylpiperazin-1-yl)pyrimidin-4-yloxy)ethoxy)ethoxy)ethoxy)ethyl 5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoate
• 英文别名: 2-(2-(2-(2-(5-(4-acrylamido-6-ammopyrimidin-2-ylthio)-6-methoxy-2-(4-methylpiperazin-1-yl)pyrimidin-4-yloxy)ethoxy)ethoxy)ethoxy)ethyl 5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoate；2-[2-[2-[2-[5-[4-amino-6-(prop-2-enoylamino)pyrimidin-2-yl]sulfanyl-6-methoxy-2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]oxyethoxy]ethoxy]ethoxy]ethyl 5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoate
• CAS: 1268273-42-2
• 化学式: C₃₅H₅₂N₁₀O₉S₂
• 分子量: 820.991
• InChiKey: PDXXUABTYPILEG-MOMDTQCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  56
• 可旋转键数：
  25
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  277
• 氢给体数：
  4
• 氢受体数：
  18

反应信息

• 作为产物：
  描述：

  2-(2-(2-(2-(2-amino-6-methoxypyrimidin-4-yloxy)ethoxy)ethoxy)ethoxy)ethanol 在 4-二甲氨基吡啶 、 copper(l) iodide 、 新铜试剂 potassium phosphate 、 N-碘代丁二酰亚胺 、 氟化氢吡啶 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 36.58h， 生成 2-(2-(2-(2-(5-(4-acrylamido-6-aminopyrimidin-2-ylthio)-6-methoxy-2-(4-methylpiperazin-1-yl)pyrimidin-4-yloxy)ethoxy)ethoxy)ethoxy)ethyl 5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoate
  参考文献：
  名称：

  [EN] HEAT SHOCK PROTEIN BINDING COMPOUNDS, COMPOSITIONS, AND METHODS FOR MAKING AND USING SAME
  [FR] COMPOSÉS DE LIAISON À UNE PROTÉINE DE CHOC THERMIQUE, COMPOSITIONS ET PROCÉDÉS POUR LES FABRIQUER ET LES UTILISER

  摘要：

  公开号：

  WO2011022440A9

文献信息

• Heat Shock Protein 70 Inhibitors. 1. 2,5′-Thiodipyrimidine and 5-(Phenylthio)pyrimidine Acrylamides as Irreversible Binders to an Allosteric Site on Heat Shock Protein 70
  作者：Yanlong Kang、Tony Taldone、Hardik J. Patel、Pallav D. Patel、Anna Rodina、Alexander Gozman、Ronnie Maharaj、Cristina C. Clement、Maulik R. Patel、Jeffrey L. Brodsky、Jason C. Young、Gabriela Chiosis

  DOI：10.1021/jm401551n

  日期：2014.2.27

  Heat shock protein 70 (Hsp70) is an important emerging. cancer. target whose inhibition may affect multiple cancer-associated signaling pathways and, moreover, result in significant cancer cell apoptosis. Despite considerable interest from both academia and pharmaceutical companies in the discovery and development of druglike Hsp70 inhibitors, little success has been reported so far. Here we describe structure activity relationship studies in the first rationally designed Hsp70 inhibitor class that binds to a novel allosteric pocket located in the N-terminal domain of the protein. These 2,5'-thiodipyrimidine and 5-(phenylthio)-pyrimidine acrylamides take advantage of an active cysteine embedded in the allosteric pocket to act as covalent protein modifiers upon binding. The study identifies derivatives 17a and 20a, which selectively bind to Hsp70 in cancer cells. Addition of high nanomolar to low micromolar concentrations of these inhibitors to cancer cells leads to a reduction in the steady-state levels of Hsp70-sheltered oncoproteins, an effect associated with inhibition of cancer cell growth and apoptosis. In summary, the described scaffolds represent a viable starting point for the development of druglike Hsp70 inhibitors as novel anticancer therapeutics.
• EP3205647A2
  申请人：——

  公开号：EP3205647A2

  公开（公告）日：2017-08-16
• [EN] HEAT SHOCK PROTEIN BINDING COMPOUNDS, COMPOSITIONS, AND METHODS FOR MAKING AND USING SAME<br/>[FR] COMPOSÉS DE LIAISON À UNE PROTÉINE DE CHOC THERMIQUE, COMPOSITIONS ET PROCÉDÉS POUR LES FABRIQUER ET LES UTILISER
  申请人：MEMORIAL SLOAN KETTERING CANCER CENTER

  公开号：WO2011022440A9

  公开（公告）日：2016-11-10