4-(N-tert-butoxycarbonylpyrrolidin-3-yl)piperidine | 929974-10-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 4-(N-tert-butoxycarbonylpyrrolidin-3-yl)piperidine
• 英文别名: tert-butyl 3-(4-piperidyl)pyrrolidine-1-carboxylate；t-butyl 3-(piperidin-4-yl)pyrrolidine-1-carboxylate；tert-Butyl 3-(piperidin-4-yl)pyrrolidine-1-carboxylate；tert-butyl 3-piperidin-4-ylpyrrolidine-1-carboxylate
• CAS: 929974-10-7
• 化学式: C₁₄H₂₆N₂O₂
• mdl: MFCD09702200
• 分子量: 254.373
• InChiKey: ZMBPMEPXLHVGRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.928
• 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：

  4-(N-tert-butoxycarbonylpyrrolidin-3-yl)piperidine 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 二甲基亚砜 、 乙腈 为溶剂， 反应 4.0h， 生成 t-butyl 2-(3-(1-(5-chloro-2-formylphenyl)piperidin-4-yl)pyrrolidin-1-yl)acetate
  参考文献：
  名称：

  PIPERAZINE CARBAMATES AND METHODS OF MAKING AND USING SAME

  摘要：

  本文提供了哌嗪氨基甲酸酯和包含该化合物的药物组合物。所述化合物和组合物可用作MAGL和/或ABHD6的调节剂。此外，所述化合物和组合物可用于治疗疼痛。

  公开号：

  US20190202801A1
• 作为产物：
  描述：

  4-吡咯烷-3-基吡啶 在 platinum(II) oxide 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 30.0~40.0 ℃ 、6.08 MPa 条件下， 反应 24.0h， 生成 4-(N-tert-butoxycarbonylpyrrolidin-3-yl)piperidine
  参考文献：
  名称：

  Synthesis of 3-substituted pyrrolidines

  摘要：

  DOI：

  10.1007/s10593-007-0005-1

文献信息

• [EN] SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1<br/>[FR] PYRIDINES SUBSTITUÉES EN TANT QU'INHIBITEURS DE DNMT1
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017216726A1

  公开（公告）日：2017-12-21

  The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  该发明涉及取代吡啶衍生物。具体而言，该发明涉及符合以下式（Iar）的化合物：（Iar）其中Yar、X1ar、X2ar、R1ar、R2ar、R3ar、R4ar和R5ar如本文所定义；或其药学上可接受的盐或前药。该发明的化合物是DNMT1的选择性抑制剂，可用于治疗癌症、癌前综合征、β血红蛋白病、镰状细胞病、镰状细胞贫血、β地中海贫血以及与DNMT1抑制相关的疾病。因此，该发明进一步涉及包含该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包含该发明化合物的药物组合物抑制DNMT1活性和治疗相关疾病的方法。
• Piperazine carbamates and methods of making and using same
  申请人：Lundbeck La Jolla Research Center, Inc.

  公开号：US10899737B2

  公开（公告）日：2021-01-26

  Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL and/or ABHD6. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

  本文提供了哌嗪氨基甲酸酯类化合物和包含上述化合物的药物组合物。所述化合物和组合物可用作 MAGL 和/或 ABHD6 的调节剂。此外，所述化合物和组合物还可用于治疗疼痛。
• Substituted pyridines as inhibitors of DNMT1
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US10975056B2

  公开（公告）日：2021-04-13

  The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及取代的吡啶衍生物。具体地说，本发明是针对符合式（Iar）的化合物： 其中 Yar、X1ar、X2ar、R1ar、R2ar、R3ar、R4ar 和 R5ar 如本文所定义；或其药学上可接受的盐或原药。 本发明的化合物是 DNMT1 的选择性抑制剂，可用于治疗癌症、癌前综合征、β 血红蛋白病疾病、镰状细胞病、镰状细胞性贫血和β 地中海贫血以及与 DNMT1 抑制相关的疾病。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物抑制 DNMT1 活性和治疗与之相关疾病的方法。
• Discovery of WD Repeat-Containing Protein 5 (WDR5)–MYC Inhibitors Using Fragment-Based Methods and Structure-Based Design
  作者：Selena Chacón Simon、Feng Wang、Lance R. Thomas、Jason Phan、Bin Zhao、Edward T. Olejniczak、Jonathan D. Macdonald、J. Grace Shaw、Caden Schlund、William Payne、Joy Creighton、Shaun R. Stauffer、Alex G. Waterson、William P. Tansey、Stephen W. Fesik

  DOI：10.1021/acs.jmedchem.0c00224

  日期：2020.4.23

  The frequent deregulation of MYC and its elevated expression via multiple mechanisms drives cells to a tumorigenic state. Indeed, MYC is overexpressed in up to similar to 50% of human cancers and is considered a highly validated anticancer target. Recently, we discovered that WD repeat-containing protein 5 (WDR5) binds to MYC and is a critical cofactor required for the recruitment of MYC to its target genes and reported the first small molecule inhibitors of the WDR5-MYC interaction using structure-based design. These compounds display high binding affinity, but have poor physicochemical properties and are hence not suitable for in vivo studies. Herein, we conducted an NMR-based fragment screening to identify additional chemical matter and, using a structure-based approach, we merged a fragment hit with the previously reported sulfonamide series. Compounds in this series can disrupt the WDR5-MYC interaction in cells, and as a consequence, we observed a reduction of MYC localization to chromatin.
• SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：EP3468953A1

  公开（公告）日：2019-04-17