6-(2,2,2-trifluoroethyl)-N-((1-(4-(trifluoromethyl)benzyl)piperidin-4-yl)methyl)thieno[2,3-d]pyrimidin-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 6-(2,2,2-trifluoroethyl)-N-((1-(4-(trifluoromethyl)benzyl)piperidin-4-yl)methyl)thieno[2,3-d]pyrimidin-4-amine
• 英文别名: 6-(2,2,2-trifluoroethyl)-N-[[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]methyl]thieno[2,3-d]pyrimidin-4-amine
• 化学式: C₂₂H₂₂F₆N₄S
• 分子量: 488.5
• InChiKey: AJVSGZCJRHLWEB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  1-叔丁氧羰基-4-氨甲基哌啶 在 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 1,2-二氯乙烷 、 异丙醇 为溶剂， 反应 3.0h， 生成 6-(2,2,2-trifluoroethyl)-N-((1-(4-(trifluoromethyl)benzyl)piperidin-4-yl)methyl)thieno[2,3-d]pyrimidin-4-amine
  参考文献：
  名称：

  Design and synthesis of benzylpiperidine inhibitors targeting the menin–MLL1 interface

  摘要：

  Menin is an essential oncogenic cofactor for mixed lineage leukemia (MLL)-mediated leukemogenesis, functioning through its direct interaction with MLL1 protein. Therefore, targeting the menin-MLL1 protein-protein interface represents a promising strategy to block MLL-mediated leukemogenesis. On the basis of co-crystal structure analysis, starting from thienopyrimidine chemotype, we have investigated the detailed structure-activity relationship of the piperazinyl-dihydrothiazole moiety. Several compounds were found with potent inhibitory activity against menin and better activities in cell-based experiments than MI-2-2. Molecular docking analysis revealed a less explored subpocket, which could be used for the design of new menin-MLL1 inhibitors. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.07.074

文献信息

• [EN] METHODS OF PROMOTING BETA CELL PROLIFERATION<br/>[FR] PROCÉDÉS DE PROMOTION DE LA PROLIFÉRATION DE CELLULES BÊTA
  申请人：KURA ONCOLOGY INC

  公开号：WO2018106818A1

  公开（公告）日：2018-06-14

  The present disclosure provides methods of promoting proliferation of a pancreatic cell. The methods are useful for the treatment of diabetes and other diseases characterized by impaired glucose tolerance.

  本公开提供了促进胰岛细胞增殖的方法。这些方法对于治疗糖尿病和其他以葡萄糖耐量受损为特征的疾病非常有用。
• COMPOSITIONS COMPRISING THIENOPYRIMIDINE AND THIENOPYRIDINE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US20160046647A1

  公开（公告）日：2016-02-18

  The present invention relates generally to thienopyrimidine and thienopyridine class compounds and methods of use thereof. In particular embodiments, the present invention provides compositions comprising thienopyrimidine and thienopyridine class compounds and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins (e.g., for the treatment of leukemia, solid cancers and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin).

  本发明涉及噻吩嘧啶和噻吩啶类化合物及其使用方法。在特定实施例中，本发明提供包含噻吩嘧啶和噻吩啶类化合物的组合物以及使用方法，以抑制Menin与MLL1、MLL2和MLL融合癌蛋白的相互作用（例如，用于治疗依赖于MLL1、MLL2、MLL融合蛋白和/或Menin活性的白血病、实体癌和其他疾病）。
• US20140275070A1
  申请人：——

  公开号：US20140275070A1

  公开（公告）日：2014-09-18
• US9216993B2
  申请人：——

  公开号：US9216993B2

  公开（公告）日：2015-12-22
• US9505781B2
  申请人：——

  公开号：US9505781B2

  公开（公告）日：2016-11-29