tert-butyl 2-((S)-2-(hydroxymethyl)-pyrrolidin-1-yl)ethylcarbamate | 863877-94-5

• 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: tert-butyl 2-((S)-2-(hydroxymethyl)-pyrrolidin-1-yl)ethylcarbamate
• 英文别名: tert-butyl N-[2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]ethyl]carbamate
• CAS: 863877-94-5
• 化学式: C₁₂H₂₄N₂O₃
• 分子量: 244.334
• InChiKey: BQCMFKQDCSXMQD-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-((S)-2-(hydroxymethyl)-pyrrolidin-1-yl)ethylcarbamate 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 反应 24.0h， 生成 3-bromo-N-[2-[(2S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrrolidin-1-yl]ethyl]pyrazolo[1,5-a]pyrimidin-5-amine
  参考文献：
  名称：

  [EN] MACROCYCLIC LRRK2 KINASE INHIBITORS
  [FR] INHIBITEURS MACROCYCLIQUES DE KINASES LRRK2

  摘要：

  本发明涉及公式（I）的新型大环化合物及含有该化合物的组合物，作为激酶抑制剂，特别是作为LRRK2（富含亮氨酸重复激酶2）的抑制剂。此外，本发明提供了制备所述化合物的方法，以及使用它们的方法，例如作为药物或诊断试剂，特别用于治疗和/或诊断由LRRK2激酶活性特征化的疾病，如包括帕金森病和阿尔茨海默病在内的神经系统紊乱。

  公开号：

  WO2016042089A1
• 作为产物：
  描述：

  2-({[(2-甲基-2-丙基)氧基]羰基}氨基)乙基甲烷磺酸酯 、 L-脯氨醇 在 sodium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以42%的产率得到tert-butyl 2-((S)-2-(hydroxymethyl)-pyrrolidin-1-yl)ethylcarbamate
  参考文献：
  名称：

  [EN] MACROCYCLIC LRRK2 KINASE INHIBITORS
  [FR] INHIBITEURS MACROCYCLIQUES DE KINASES LRRK2

  摘要：

  本发明涉及公式（I）的新型大环化合物及含有该化合物的组合物，作为激酶抑制剂，特别是作为LRRK2（富含亮氨酸重复激酶2）的抑制剂。此外，本发明提供了制备所述化合物的方法，以及使用它们的方法，例如作为药物或诊断试剂，特别用于治疗和/或诊断由LRRK2激酶活性特征化的疾病，如包括帕金森病和阿尔茨海默病在内的神经系统紊乱。

  公开号：

  WO2016042089A1

文献信息

• Macrocyclic LRRK2 kinase inhibitors
  申请人：Oncodesign S.A.

  公开号：US10377772B2

  公开（公告）日：2019-08-13

  The present invention relates to novel macrocyclic compounds of formula (I) and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of LRRK2 (Leucine-Rich Repeat Kinase 2). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine or diagnostic agent, in particular for the treatment and/or diagnosis of diseases characterized by LRRK2 kinase activity such as neurological disorders including Parkinson's disease and Alzheimer's disease.

  本发明涉及新颖的式(I)大环化合物和含有所述化合物的组合物，所述化合物可作为激酶抑制剂，特别是作为LRRK2（亮氨酸富重复激酶2）的抑制剂。此外，本发明还提供了制备所公开化合物的工艺以及使用这些化合物的方法，例如将其用作药物或诊断剂，特别是用于治疗和/或诊断以 LRRK2 激酶活性为特征的疾病，如神经系统疾病，包括帕金森病和阿尔茨海默病。
• Synthesis of DNA-Directed Pyrrolidinyl and Piperidinyl Confined Alkylating Chloroalkylaminoanthraquinones:  Potential for Development of Tumor-Selective <i>N</i>-Oxides
  作者：Klaus Pors、Steven D. Shnyder、Paul H. Teesdale-Spittle、John A. Hartley、Mire Zloh、Mark Searcey、Laurence H. Patterson

  DOI：10.1021/jm0608154

  日期：2006.11.30

  A novel series of 1,4-disubstituted chloroethylaminoanthraquinones, containing alkylating chloroethylamino functionalities as part of a rigid piperidinyl or pyrrolidinyl ring-system, have been prepared. The target compounds were prepared by ipso-displacement of halides of various anthraquinone chromophores by either hydroxylated or chlorinated piperidinyl- or pyrrolidinyl-alkylamino side chains. The chloroethylaminoanthraquinones were shown to alkylate guanine residues of linearized pBR322 (1-20 mu M), and two symmetrically 1,4-disubstituted anthraquinones (compounds 14 and 15) were shown to interstrand cross-link DNA in the low nM range. Several 1,4-disubstituted chloroethylaminoanthraquinones were potently cytotoxic (IC(50) values: <= 40 nM) in human ovarian cancer A2780 cells. Two agents (compounds 18 and 19) exhibited mean GI(50) values of 96 nM and 182 nM, respectively, in the NCI human tumor cell line panel. Derivatization of the potent DNA cross-linking agent 15 to an N-oxide resulted in loss of the DNA unwinding, DNA interstrand cross-linking and cytotoxic activity of the parent molecule.
• MACROCYCLIC LRRK2 KINASE INHIBITORS
  申请人：Oncodesign S.A.

  公开号：US20170240565A1

  公开（公告）日：2017-08-24

  The present invention relates to novel macrocyclic compounds of formula (I) and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of LRRK2 (Leucine-Rich Repeat Kinase 2). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine or diagnostic agent, in particular for the treatment and/or diagnosis of diseases characterized by LRRK2 kinase activity such as neurological disorders including Parkinson's disease and Alzheimer's disease.