tert-butyl (3-(3-formylphenoxy)propyl)carbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: tert-butyl (3-(3-formylphenoxy)propyl)carbamate
• 英文别名: tert-butyl N-[3-(3-formylphenoxy)propyl]carbamate
• 化学式: C₁₅H₂₁NO₄
• 分子量: 279.336
• InChiKey: GDSBMQGBSMSMTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(piperidin-4-yl)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-amine 、 tert-butyl (3-(3-formylphenoxy)propyl)carbamate 在 溶剂黄146 、 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 以75%的产率得到tert-butyl (3-(3-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)phenoxy)propyl)carbamate
  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
• 作为产物：
  描述：

  N-Boc-3-氨基丙基溴 、 间羟基苯甲醛 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以86%的产率得到tert-butyl (3-(3-formylphenoxy)propyl)carbamate
  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

• Spiro bicyclic inhibitors of menin-MLL interaction
  申请人：Janssen Pharmaceutica NV

  公开号：US11220517B2

  公开（公告）日：2022-01-11

  The present invention relates to compounds of formula (I): wherein the variables have the meaning defined in the Specification. The compounds according to the present invention are useful for therapy and/or prophylaxis in a mammal, and in particular to spiro bicyclic compounds, pharmaceutical composition comprising such compounds, and their use as menin/MLL protein/protein interaction inhibitors, useful for treating diseases such as cancer, myelodysplastic syndrome (MDS) and diabetes.

  本发明涉及式（I）化合物： 其中的变量具有说明书中定义的含义。根据本发明的化合物可用于哺乳动物的治疗和/或预防，特别是螺环双环化合物、包含此类化合物的药物组合物，以及它们作为 menin/MLL 蛋白/蛋白相互作用抑制剂的用途，可用于治疗癌症、骨髓增生异常综合征（MDS）和糖尿病等疾病。
• SPIRO BICYCLIC INHIBITORS OF MENIN-MLL INTERACTION
  申请人：Janssen Pharmaceutica NV

  公开号：US20190211036A1

  公开（公告）日：2019-07-11

  The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to spiro bicyclic compounds, pharmaceutical composition comprising such compounds, and their use as menin/MLL protein/protein interaction inhibitors, useful for treating diseases such as cancer, myelodysplastic syndrome (MDS) and diabetes.