R-哌啶-3-羧酸叔丁酯 | 912807-35-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: R-哌啶-3-羧酸叔丁酯
• 英文名称: tert-butyl (R)-nipecotate
• 英文别名: (R)-3-N-tert-butoxycarbonylaminopiperidine；tert-butyl (R)-piperidin-3-ylcarboxylate；tert-butyl (3R)-piperidine-3-carboxylate
• CAS: 912807-35-3
• 化学式: C₁₀H₁₉NO₂
• 分子量: 185.266
• InChiKey: RHNAXBBEIVHVQT-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  R-哌啶-3-羧酸叔丁酯 在 ammonium hydroxide 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Challenges in the Development of a Thiol-Based Broad-Spectrum Inhibitor for Metallo-β-Lactamases

  摘要：

  Pathogens, expressing metallo-beta-lactamases (MBLs), become resistant against most beta-lactam antibiotics. Besides the dragging search for new antibiotics, development of MBL inhibitors would be an alternative weapon against resistant bacterial pathogens. Inhibition of resistance enzymes could restore the antibacterial activity of beta-lactams. Various approaches to MBL inhibitors are described; among others, the promising motif of a zinc coordinating thiol moiety is very popular. Nevertheless, since the first report of a thiol-based MBL inhibitor (thiomandelic acid) in 2001, no steps in development of thiol based MBL inhibitors were reported that go beyond clinical isolate testing. In this study, we report on the synthesis and biochemical characterization of thiol-based MBL inhibitors and highlight the challenges behind the development of thiol-based compounds, which exhibit good in vitro activity toward a broad spectrum of MBLs, selectivity against human off targets, and reasonable activity against clinical isolates.

  DOI：

  10.1021/acsinfecdis.7b00129
• 作为产物：
  描述：

  (R)-piperidine-1,3-dicarboxylic acid 1-benzyl ester 3-tert-butyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 8.0h， 以90%的产率得到R-哌啶-3-羧酸叔丁酯
  参考文献：
  名称：

  Stereoselective Preparation of a Cyclopentane-Based NK1 Receptor Antagonist Bearing an Unsymmetrically Substituted Sec−Sec Ether

  摘要：

  A highly efficient synthesis of the potent and selective NK-1 receptor antagonist 1 is described. The key transformation involved the etherification reaction between cyclopentanol 12 and chiral imidate 30 which was catalyzed by HBF4 to initially give ether 14 as a 17:1 mixture of diastereomers and in 75% combined yield. The diastereoselectivity was upgraded to 109:1 by crystallization of the triethylamine solvate 44 which was isolated in 54% yield from 12. Mechanistic studies confirmed that the etherification reaction proceeds through an unprecedented S(N)2 reaction pathway under typical S(N)1 reaction conditions.

  DOI：

  10.1021/jo061268x

文献信息

• NITROGENOUS HETEROCYCLIC COMPOUND, PREPARATION METHOD, INTERMEDIATE, COMPOSITION, AND APPLICATION
  申请人：SHANGHAI PHARMACEUTICALS HOLDING CO., LTD.

  公开号：US20200190091A1

  公开（公告）日：2020-06-18

  A nitrogenous heterocyclic compound, a preparation method, an intermediate, a composition, and an application. The present invention provides a nitrogenous heterocyclic compound as represented by formula I, pharmaceutically acceptable salts thereof, enantiomers thereof, diastereoisomers thereof, tautomers thereof, solvates thereof, metabolites thereof, or prodrugs thereof. The compound has high inhibitory activity against ErbB2 tyrosine kinase, has good inhibitory activity against human breast cancer cells BT-474, human gastric cancer cells NCI-N87 and the like with high expression of ErbB2, and in addition has relatively weak inhibitory activity against EGFR kinase, that is, the compound is an EGFR/ErbB2 double target inhibitor that attenuates EGFR kinase inhibitory activity or a small-molecule inhibitor having selectivity for an ErbB2 target. (I)

  一种含氮杂环化合物，一种制备方法，一种中间体，一种组合物和一种应用。本发明提供一种由式I表示的含氮杂环化合物，其药学上可接受的盐，其对映体，其非对映异构体，其互变异构体，其溶剂合物，其代谢物或其前药。该化合物对ErbB2酪氨酸激酶具有高抑制活性，对表达ErbB2高的人类乳腺癌细胞BT-474，人类胃癌细胞NCI-N87等具有良好的抑制活性，并且对EGFR激酶具有相对较弱的抑制活性，即该化合物是一种减弱EGFR激酶抑制活性的EGFR/ErbB2双靶点抑制剂或具有选择性作用于ErbB2靶点的小分子抑制剂。 (I)
• [EN] SUBSTITUTED PYRIMIDINES AND METHODS OF USE<br/>[FR] PYRIMIDINES SUBSTITUÉES ET MÉTHODES D'UTILISATION
  申请人：THERAVANCE BIOPHARMA R&D IP LLC

  公开号：WO2021203131A1

  公开（公告）日：2021-10-07

  The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.

  本公开提供了抑制活性素受体样激酶5（ALK5）的抑制剂。还公开了调节ALK5活性的方法以及治疗由ALK5介导的疾病的方法。
• SOLID STATE FORMS OF LINAGLIPTIN
  申请人：Metsger Leonid

  公开号：US20130123282A1

  公开（公告）日：2013-05-16

  The present invention provides solid state forms of Linagliptin, processes for preparing the solid state forms, and pharmaceutical compositions thereof.

  本发明提供了利那格列汀的固态形式，以及制备这些固态形式和药物组合物的方法。
• Discovery and Mechanistic Study of Novel <i>Mycobacterium tuberculosis</i> ClpP1P2 Inhibitors
  作者：Yang Yang、Ninglin Zhao、Xin Xu、Yuanzheng Zhou、Baozhu Luo、Jiangnan Zhang、Jing Sui、Jiasheng Huang、Zhiqiang Qiu、Xuelian Zhang、Jumei Zeng、Lang Bai、Rui Bao、Youfu Luo

  DOI：10.1021/acs.jmedchem.3c01054

  日期：2023.12.28

  misfolded proteins plays a critical role in proteome homeostasis. MtbClpP1P2, a ClpP enzyme complex, is required for survival in Mycobacterium tuberculosis, and it is therefore considered as a promising target for the development of antituberculosis drugs. Here, we discovered that cediranib and some of its derivatives are potent MtbClpP1P2 inhibitors and suppress M. tuberculosis growth. Protein pull-down

  酪蛋白分解酶 P (ClpP) 负责对受损或错误折叠的蛋白质进行蛋白水解，在蛋白质组稳态中发挥着关键作用。 MtbClpP1P2是一种ClpP酶复合物，是结核分枝杆菌生存所必需的，因此被认为是开发抗结核药物的有希望的靶点。在这里，我们发现西地尼布及其一些衍生物是有效的 MtbClpP1P2 抑制剂，可抑制结核分枝杆菌的生长。蛋白质下拉和功能丧失测定验证了西地尼布及其活性衍生物对 MtbClpP1P2 的原位靶向。结构和突变研究表明，西地尼布通过与 MtbClpP1 亚基赤道柄结构域的变构袋结合而与 MtbClpP1P2 结合，与其他已知的 ClpP 调节剂相比，这代表了一种独特的结合模式。这些发现为我们提供了抗结核治疗合理药物设计的见解，并为我们理解 MtbClpP1P2 的生物活性提供了启示。
• Stereoselective Preparation of a Cyclopentane-Based NK1 Receptor Antagonist Bearing an Unsymmetrically Substituted Sec−Sec Ether
  作者：Jeffrey T. Kuethe、Jean-Francois Marcoux、Audrey Wong、Jimmy Wu、Michael C. Hillier、Peter G. Dormer、Ian W. Davies、David L. Hughes

  DOI：10.1021/jo061268x

  日期：2006.9.1

  A highly efficient synthesis of the potent and selective NK-1 receptor antagonist 1 is described. The key transformation involved the etherification reaction between cyclopentanol 12 and chiral imidate 30 which was catalyzed by HBF4 to initially give ether 14 as a 17:1 mixture of diastereomers and in 75% combined yield. The diastereoselectivity was upgraded to 109:1 by crystallization of the triethylamine solvate 44 which was isolated in 54% yield from 12. Mechanistic studies confirmed that the etherification reaction proceeds through an unprecedented S(N)2 reaction pathway under typical S(N)1 reaction conditions.