tert-butyl (3-bromoprop-2-yn-1-yl)carbamate | 1160357-42-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl (3-bromoprop-2-yn-1-yl)carbamate
• 英文别名: CarbaMic acid, N-(3-broMo-2-propyn-1-yl)-, 1,1-diMethylethyl ester；tert-butyl N-(3-bromoprop-2-ynyl)carbamate
• CAS: 1160357-42-5
• 化学式: C₈H₁₂BrNO₂
• 分子量: 234.093
• InChiKey: QOXBTVNMYIHJJR-UHFFFAOYSA-N

物化性质

• 密度：
  1.381±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  tert-butyl (3-bromoprop-2-yn-1-yl)carbamate 在 manganese(IV) oxide 、 盐酸羟胺 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 异丙胺 、 copper(l) chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 tert-butyl (5-(2-(4-((3-(4-hydroxy-6-(thiophen-2-yl)pyrimidin-2-yl)piperidin-1-yl)methyl)-1Himidazol-1-yl)pyrimidin-5-yl)penta-2,4-diyn-1-yl)carbamate
  参考文献：
  名称：

  Gram-Negative Antibiotic Active Through Inhibition of an Essential Riboswitch

  摘要：

  Multidrug-resistant Gram-negative (GN) infections for which there are few available treatment options are increasingly common. The development of new antibiotics for these pathogens is challenging because of the inability of most small molecules to accumulate inside GN bacteria. Using recently developed predictive guidelines for compound accumulation in Escherichia coli, we have converted the antibiotic Ribocil C, which targets the flavin mononucleotide (FMN) riboswitch, from a compound lacking whole-cell activity against wild-type GN pathogens into a compound that accumulates to a high level in E. coli, is effective against Gram-negative clinical isolates, and has efficacy in mouse models of GN infections. This compound allows for the first assessment of the translational potential of FMN riboswitch binders against wild-type Gram-negative bacteria.

  DOI：

  10.1021/jacs.0c04427
• 作为产物：
  描述：

  N-Boc-氨基丙炔 在 N-溴代丁二酰亚胺(NBS) 、 silver nitrate 作用下， 以 丙酮 为溶剂， 生成 tert-butyl (3-bromoprop-2-yn-1-yl)carbamate
  参考文献：
  名称：

  中性三原子组分与末端炔烃的 (3 + 2) 环加成反应中的铜和银催化

  摘要：

  将铜催化的叠氮化物-炔烃偶联 (CuAAC) 引入 1,3-偶极环加成反应对于其在合成化学中的普及以及在多个其他科学领域的应用至关重要。当造币金属乙炔化物中间体参与环化过程时观察到的反应速率提高极大地扩展了可以与末端炔发生(3+2)环加成的结构和条件范围。在此，我们报告了在性质和水平上相当的速率增强是由铜和银催化剂在末端炔烃与“中性”三原子组分（TAC）（特别是炔基硫醚）的分子内（3 + 2）环加成中引起的。通过对反应优化、实验和 DFT 机理研究的仔细观察，提出了一条涉及质子耦合环金属化关键步骤的途径。已开发的催化条件集使我们能够克服先前由“中性”TAC 的热促进 (3 + 2) 环加成所带来的几个范围限制，从而扩大了其合成和应用潜力。

  DOI：

  10.1021/jacs.3c06533

文献信息

• [EN] CATHEPSIN INHIBITORS<br/>[FR] INHIBITEURS DE LA CATHEPSINE
  申请人：ACADEMISCH ZIEKENHUIS LEIDEN

  公开号：WO2019112426A1

  公开（公告）日：2019-06-13

  This invention relates to compounds that are useful as inhibitors, in particular as inhibitors of Cathepsin K (CatK), and to a method of inhibiting cathepsin activity, comprising administering a compound or formulation comprising a compound according to the invention.

  这项发明涉及一种作为抑制剂有用的化合物，特别是作为Cathepsin K（CatK）的抑制剂，并涉及一种抑制蛋白酶活性的方法，包括给予根据该发明的化合物或配方的化合物。
• The Alkyne Moiety as a Latent Electrophile in Irreversible Covalent Small Molecule Inhibitors of Cathepsin K
  作者：Elma Mons、Ineke D. C. Jansen、Jure Loboda、Bjorn R. van Doodewaerd、Jill Hermans、Martijn Verdoes、Constant A. A. van Boeckel、Peter A. van Veelen、Boris Turk、Dusan Turk、Huib Ovaa

  DOI：10.1021/jacs.8b11027

  日期：2019.2.27

  Irreversible covalent inhibitors can have a beneficial pharmacokinetic/pharmacodynamics profile but are still often avoided due to the risk of indiscriminate covalent reactivity and the resulting adverse effects. To overcome this potential liability, we introduced an alkyne moiety as a latent electrophile into small molecule inhibitors of cathepsin K (CatK). Alkyne-based inhibitors do not show indiscriminate

  不可逆共价抑制剂可能具有有益的药代动力学/药效学特征，但由于存在不加区别的共价反应性和由此产生的不良反应的风险，仍然经常被避免使用。为了克服这种潜在的缺点，我们将炔部分作为潜在的亲电子试剂引入组织蛋白酶 K (CatK) 的小分子抑制剂中。晶体结构分析证实，基于炔烃的抑制剂不表现出任意的硫醇反应性，但通过与催化半胱氨酸残基形成不可逆共价键，有效抑制 CatK 蛋白酶活性。共价键形成速率 (kinact) 与炔部分的亲电性不相关，表明接近驱动的反应性。CatK 介导的骨吸收抑制作用已在人类破骨细胞中得到验证。总之，这项工作说明了炔烃作为小分子抑制剂中潜在亲电子试剂的潜力，从而能够开发具有改进安全性的不可逆共价抑制剂。
• Stereoselective Synthesis of d 4-(S)-Lysine from (S)-Serine
  作者：Uli Kazmaier、Michael Kohr

  DOI：10.1055/s-0037-1610221

  日期：2018.12

  Abstract Tetradeuterated (S)-lysine can easily be obtained from protected (S)-serine in a few steps including a Cu-mediated cross coupling and subsequent platinum-catalysed deuteration. Tetradeuterated (S)-lysine can easily be obtained from protected (S)-serine in a few steps including a Cu-mediated cross coupling and subsequent platinum-catalysed deuteration.

  摘要 可以在几个步骤中轻松地从受保护的（S）-丝氨酸中获得四氢呋喃（S）-赖氨酸，这些步骤包括Cu介导的交叉偶联和随后的铂催化的氘化。 可以在几个步骤中轻松地从受保护的（S）-丝氨酸中获得四氢呋喃（S）-赖氨酸，这些步骤包括Cu介导的交叉偶联和随后的铂催化的氘化。
• Zeo-Click Synthesis: Copper-Zeolite-Catalyzed Synthesis of Ynamides
  作者：Hassina Harkat、Sophie Borghèse、Matteo De Nigris、Serguei Kiselev、Valérie Bénéteau、Patrick Pale

  DOI：10.1002/adsc.201400189

  日期：2014.12.15

  AbstractCopper(I)‐zeolites, especially copper(I)‐ultra stable Y zeolite (USY), are very efficient heterogeneous catalysts for the coupling of functionalized 1‐bromoalkynes and various nitrogen derivatives. Under these conditions, sulfonylated alkyl‐ or arylamines and various N‐heterocycles, such as oxazolidinones or indoles, could be efficiently transformed into the corresponding N‐alkynyl derivatives. However, imidazoles gave addition products rather than coupling products. The reaction conditions proved compatible with a variety of functional and protecting groups. Such zeolitic catalysts can be recycled and reused at least five times without significant deactivation. Low catalyst loading could be used (4 mol%) and as low as 0.8 mol% of this heterogeneous copper catalyst still gave good conversion and yields.magnified image
• Mapping Ligand Interactions of Bromodomains BRD4 and ATAD2 with FragLites and PepLites─Halogenated Probes of Druglike and Peptide-like Molecular Interactions
  作者：Gemma Davison、Mathew P. Martin、Shannon Turberville、Selma Dormen、Richard Heath、Amy B. Heptinstall、Marie Lawson、Duncan C. Miller、Yi Min Ng、James N. Sanderson、Ian Hope、Daniel J. Wood、Céline Cano、Jane A. Endicott、Ian R. Hardcastle、Martin E. M. Noble、Michael J. Waring

  DOI：10.1021/acs.jmedchem.2c01357

  日期：2022.11.24