1,1-dimethylethyl 4-({[(1S,2R)-2-phenylcyclopropyl]amino}methyl)-1-piperidinecarboxylate | 1401966-32-2

• 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: 1,1-dimethylethyl 4-({[(1S,2R)-2-phenylcyclopropyl]amino}methyl)-1-piperidinecarboxylate
• 英文别名: tert-butyl 4-[[[(1S,2R)-2-phenylcyclopropyl]amino]methyl]piperidine-1-carboxylate
• CAS: 1401966-32-2
• 化学式: C₂₀H₃₀N₂O₂
• 分子量: 330.47
• InChiKey: TVZRCZXWTLWMHW-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl 4-({[(1S,2R)-2-phenylcyclopropyl]amino}methyl)-1-piperidinecarboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 2.0h， 以82%的产率得到
  参考文献：
  名称：

  Tranylcypromine and 6-trifluoroethyl thienopyrimidine hybrid as LSD1 inhibitor

  摘要：

  Tranylcypromine moiety extracted from LSD1 inhibitors and 6-trifluoroethyl thienopyrimidine moiety from menin-MLL1 PPI inhibitors were merged to give new chemotypes for medicinal chemistry study. Among 15 new compounds prepared in this work, some exhibited nanomolar LSD1 activity and good selectivity over MAO-A/B, low micromolar menin-MLL1 PPI inhibitory activity, as well as submicromolar MV4-11 antiprofilative activities. Intracellular LSD1 engagement of compounds with higher enzymatic and antiproliferative activities was confirmed by CD86 mRNA up-regulation experiments.

  DOI：

  10.1016/j.bmcl.2019.01.017
• 作为产物：
  描述：

  、 1-叔丁氧羰基哌啶-4-甲醛 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 1,1-dimethylethyl 4-({[(1S,2R)-2-phenylcyclopropyl]amino}methyl)-1-piperidinecarboxylate
  参考文献：
  名称：

  Tranylcypromine and 6-trifluoroethyl thienopyrimidine hybrid as LSD1 inhibitor

  摘要：

  Tranylcypromine moiety extracted from LSD1 inhibitors and 6-trifluoroethyl thienopyrimidine moiety from menin-MLL1 PPI inhibitors were merged to give new chemotypes for medicinal chemistry study. Among 15 new compounds prepared in this work, some exhibited nanomolar LSD1 activity and good selectivity over MAO-A/B, low micromolar menin-MLL1 PPI inhibitory activity, as well as submicromolar MV4-11 antiprofilative activities. Intracellular LSD1 engagement of compounds with higher enzymatic and antiproliferative activities was confirmed by CD86 mRNA up-regulation experiments.

  DOI：

  10.1016/j.bmcl.2019.01.017

文献信息

• CYCLOPROPYLAMINES AS LSD1 INHIBITORS
  申请人：INCYTE CORPORATION

  公开号：US20150225394A1

  公开（公告）日：2015-08-13

  The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

  本发明涉及环丙胺衍生物，这些衍生物是LSD1抑制剂，可用于治疗癌症等疾病。
• Novel dual LSD1/HDAC6 inhibitors for the treatment of multiple myeloma
  作者：M Naveen Sadhu、Dhanalakshmi Sivanandhan、Chandru Gajendran、Subramanyam Tantry、Purushottam Dewang、Kannan Murugan、Srinatha Chickamunivenkatappa、Mohd Zainuddin、Sreekala Nair、Krishnakumar Vaithilingam、Sridharan Rajagopal

  DOI：10.1016/j.bmcl.2020.127763

  日期：2021.2

  HDAC6 selective dual inhibitors to target MM. Our dual inhibitor compound 1 shows superior potency in multiple MM cell lines. In MM.1S xenograft model compound 1 shows superior efficacy compared to single agent LSD1 and HDAC6 inhibitors by oral administration and is well tolerated. Further evaluation of the molecule in other cancers is in progress.

  赖氨酸特异性脱甲基酶1（LSD1）和HDAC6是与多种疾病（包括癌症）相关的表观遗传蛋白，这些蛋白的联合抑制对治疗某些癌症（如AML，MM和实体瘤）可能非常有益。多发性骨髓瘤（MM）是一种具有挑战性的癌症，具有快速复发率，其中需要一小时的治疗方法。我们已经设计和开发了针对MM的新型LSD1和HDAC6选择性双重抑制剂。我们的双重抑制剂化合物1在多种MM细胞系中显示出卓越的功效。在MM.1S异种移植模型化合物1中，口服单药LSD1和HDAC6抑制剂比单药LSD1和HDAC6抑制剂具有更高的疗效，并且耐受性良好。该分子在其他癌症中的进一步评估正在进行中。
• JP5813855
  申请人：——

  公开号：——

  公开（公告）日：——
• USE OF A COMBINATIONAL THERAPY OF LSD1 INHIBITORS WITH CDK2 INHIBITORS IN THE TREATMENT OF CANCER
  申请人：Rasna Therapeutics Limited

  公开号：US20180311245A1

  公开（公告）日：2018-11-01

  The present disclosure relates to methods of treating cancer and pharmaceutical compositions for use in the treatment of cancer, including LSD1-inhibitor-resistant cancers, comprising administering to a subject an effective amount of a CDK2 inhibitor and an effective amount of a LSD1 inhibitor.
• USE OF A COMBINATIONAL THERAPY OF LSD1 INHIBITORS WITH P21 ACTIVATORS IN THE TREATMENT OF CANCER
  申请人：Istituto Europeo di Oncologia S.r.l.

  公开号：US20210100800A1

  公开（公告）日：2021-04-08

  The present disclosure relates to methods of treating cancer and pharmaceutical compositions for use in the treatment of cancer, including LSD1-inhibitor-resistant cancers, comprising administering to a subject an effective amount of a cell cycle inhibitor, such as a CDK4/6 inhibitor or a p21 enhancer, and an effective amount of a LSD1 inhibitor.