3-糠酰异硫氰酸酯 | 115156-71-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 中文名称: 3-糠酰异硫氰酸酯
• 英文名称: 3-furoyl isothiocyanate
• 英文别名: Furan-3-carbonyl isothiocyanate
• CAS: 115156-71-3
• 化学式: C₆H₃NO₂S
• 分子量: 153.161
• InChiKey: MPNLVVTZHYWUKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-糠酰异硫氰酸酯 、 对三氟甲氧基苯胺 以 乙醚 、 环己烷 为溶剂， 反应 5.0h， 以69%的产率得到1-(furan-3-carbonyl)-3-[4-(trifluoromethoxy)phenyl]-thiourea
  参考文献：
  名称：

  Furan derivatives of substituted phenylthiourea: spectral studies, semi-empirical quantum-chemical calculations and X-ray structure analyses

  摘要：

  Fifty new derivatives of 1-(furan-2-carbonyl)- and 1-(furan-3-carbonyl)-3-phenyl substituted thiourea have been synthesised and identified. Intramolecular hydrogen bonds were investigated in detail, using IR spectroscopy. The three-level Fermi resonance effect in the IR spectra was analysed after deconvolution and band separation. Semi-empirical quantum-chemical calculations (AMI and PM3) support the results of the IR spectroscopic studies. X-ray single crystal diffraction analyses of four selected compounds, namely 1-(furan-3-carbonyl)-3(2-trifluoromethyl-phenyl)-thiourea (le), 1-(2-methyl-furan-3-carbonyl)-3-(2-trifluoromethyl-phenyl)-thiourea (2e), 1-(2,6-dichlorophenyl)-3-(2-methyl-furan-3-carbonyl)-thiourea (2n) and 1-(4-methoxyphenyl)-3-(3-methyl-2-furan-carbonyl)-thiourea (3e), corroborated the molecular and crystal structure of these compounds. Relatively strong intramolecular hydrogen bonds of the N-H...O=C type as well as intermolecular two-centred and bifurcated three-centred hydrogen bonds were observed, confirming the results of the IR spectral study and the semi-empirical quantum-chemical calculations. A variety of intermolecular interactions, yielding the supramolecular architectures in the four crystalline compounds, are discussed in detail. (c) 2005 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molstruc.2005.02.014
• 作为产物：
  描述：

  3-呋喃甲酰氯 、 potassium thioacyanate 以 丙酮 为溶剂， 生成 3-糠酰异硫氰酸酯
  参考文献：
  名称：

  基于芳酰基胍的Xa因子抑制剂：BMS-344577的发现

  摘要：

  我们报告设计和合成的新型的N，N'-二取代的芳基胍基内酰胺衍生物作为有效和口服活性FXa抑制剂。通过结构-活性关系（SAR）研究，发现了烟酰胍22作为有效的FXa抑制剂（FXa IC 50  = 4 nM，EC 2×PT  = 7μM）。然而，有效的CYP3A4抑制活性（IC 50  = 0.3μM）的22排除其进一步发展。对与FXa结合的化合物22的X射线晶体结构的详细分析表明，取代基位于22的烟酰基基团的6位上会暴露在溶剂中，这表明减弱不需要的CYP活性的努力可以集中在这个位置上，而不会显着影响FXa的效力。对6-取代的烟酰胺基胍进行的进一步SAR研究导致发现了6-（二甲基氨基甲酰基）烟酰胍36（BMS-344577，IC 50  = 9 nM，EC 2×PT  = 2.5μM），发现具有选择性，口服有效的FXa抑制剂，在动物模型中具有出色的体外耐受性，良好的药代动力学和药效学。

  DOI：

  10.1016/j.bmcl.2009.10.084

文献信息

• Novel inhibitors of Staphylococcus aureus RnpA that synergize with mupirocin
  作者：Nicole Lounsbury、Tess Eidem、Jennifer Colquhoun、George Mateo、Magid Abou-Gharbia、Paul M. Dunman、Wayne E. Childers

  DOI：10.1016/j.bmcl.2018.01.022

  日期：2018.4

  relevant strains of S. aureus, including MRSA. Structure-activity studies aimed at improving potency and replacing the potentially metabotoxic furan moiety led to the identification of a number of more potent analogs. Many of these new analogs possessed overt cellular toxicity that precluded their use as antibiotics but two derivatives, including compound 5o, displayed an impressive synergy with mupirocin

  我们最近发现RnpA是耐甲氧西林金黄色葡萄球菌（MRSA）的有希望的新药物发现靶标。RnpA是一种必需蛋白，被认为可以执行两个必需的细胞过程。作为RNA的一部分，Rnpa介导RNA降解。与rnpB结合可形成tRNA成熟所需的RNase P卤酶。高通量筛选确定RNPA2000是RnpA相关活性的抑制剂，对临床相关金黄色葡萄球菌具有抗菌活性。，包括MRSA。旨在提高效力并取代潜在的代谢毒性呋喃部分的结构活性研究导致鉴定出许多更有效的类似物。许多新的类似物具有明显的细胞毒性，因此不能用作抗生素，但包括衍生物5o在内的两种衍生物与莫匹罗星具有令人印象深刻的协同作用，后者是一种用于MSRA非定殖的抗生素，其有效性最近因细菌耐药性而受到损害。根据我们的研究结果，像5o这样的化合物可能最终可用于使对莫匹罗星耐药的细菌对莫匹罗星重新敏感。
• Design and synthesis of indole, 2,3-dihydro-indole, and 3,4-dihydro-2H-quinoline-1-carbothioic acid amide derivatives as novel HCV inhibitors
  作者：Iou-Jiun Kang、Li-Wen Wang、Sheng-Ju Hsu、Chung-Chi Lee、Yen-Chun Lee、Yen-Shian Wu、Tsu-An Hsu、Andrew Yueh、Yu-Sheng Chao、Jyh-Haur Chern

  DOI：10.1016/j.bmcl.2009.06.009

  日期：2009.8

  An efficient synthetic methodology to provide indole, 2,3-dihydro-indole, and 3,4-dihydro-2H-quinoline-1-carbothioic acid amide derivatives is described. These conformationally restricted heterobicyclic scaffolds were evaluated as a novel class of HCV inhibitors. Introduction of an acyl group at the NH2 of the thiourea moiety has been found to enhance inhibitory activity. The chain length and the position of the alkyl group on the indoline aromatic ring markedly influenced anti-HCV activity. The indoline scaffold was more potent than the corresponding indole and tetrahydroquinoline scaffolds and analogue 31 displayed excellent activity (EC50 = 510 nM) against HCV without significant cytotoxicity (CC50 > 50 mu M). (C) 2009 Elsevier Ltd. All rights reserved.
• Furan derivatives of substituted phenylthiourea: spectral studies, semi-empirical quantum-chemical calculations and X-ray structure analyses
  作者：Ol'ga Hritzová、Juraj Černák、Peter Šafař、Zdenka Frőhlichová、Ingeborg Csőregh

  DOI：10.1016/j.molstruc.2005.02.014

  日期：2005.5

  Fifty new derivatives of 1-(furan-2-carbonyl)- and 1-(furan-3-carbonyl)-3-phenyl substituted thiourea have been synthesised and identified. Intramolecular hydrogen bonds were investigated in detail, using IR spectroscopy. The three-level Fermi resonance effect in the IR spectra was analysed after deconvolution and band separation. Semi-empirical quantum-chemical calculations (AMI and PM3) support the results of the IR spectroscopic studies. X-ray single crystal diffraction analyses of four selected compounds, namely 1-(furan-3-carbonyl)-3(2-trifluoromethyl-phenyl)-thiourea (le), 1-(2-methyl-furan-3-carbonyl)-3-(2-trifluoromethyl-phenyl)-thiourea (2e), 1-(2,6-dichlorophenyl)-3-(2-methyl-furan-3-carbonyl)-thiourea (2n) and 1-(4-methoxyphenyl)-3-(3-methyl-2-furan-carbonyl)-thiourea (3e), corroborated the molecular and crystal structure of these compounds. Relatively strong intramolecular hydrogen bonds of the N-H...O=C type as well as intermolecular two-centred and bifurcated three-centred hydrogen bonds were observed, confirming the results of the IR spectral study and the semi-empirical quantum-chemical calculations. A variety of intermolecular interactions, yielding the supramolecular architectures in the four crystalline compounds, are discussed in detail. (c) 2005 Elsevier B.V. All rights reserved.
• Aroylguanidine-based factor Xa inhibitors: The discovery of BMS-344577
  作者：Yan Shi、Chi Li、Stephen P. O’Connor、Jing Zhang、Mengxiao Shi、Sharon N. Bisaha、Ying Wang、Doree Sitkoff、Andrew T. Pudzianowski、Christine Huang、Herbert E. Klei、Kevin Kish、Joseph Yanchunas、Eddie C.-K. Liu、Karen S. Hartl、Steve M. Seiler、Thomas E. Steinbacher、William A. Schumacher、Karnail S. Atwal、Philip D. Stein

  DOI：10.1016/j.bmcl.2009.10.084

  日期：2009.12

  We report the design and synthesis of a novel class of N,N′-disubstituted aroylguanidine-based lactam derivatives as potent and orally active FXa inhibitors. The structure–activity relationships (SAR) investigation led to the discovery of the nicotinoyl guanidine 22 as a potent FXa inhibitor (FXa IC50 = 4 nM, EC2×PT = 7 μM). However, the potent CYP3A4 inhibition activity (IC50 = 0.3 μM) of 22 precluded

  我们报告设计和合成的新型的N，N'-二取代的芳基胍基内酰胺衍生物作为有效和口服活性FXa抑制剂。通过结构-活性关系（SAR）研究，发现了烟酰胍22作为有效的FXa抑制剂（FXa IC 50  = 4 nM，EC 2×PT  = 7μM）。然而，有效的CYP3A4抑制活性（IC 50  = 0.3μM）的22排除其进一步发展。对与FXa结合的化合物22的X射线晶体结构的详细分析表明，取代基位于22的烟酰基基团的6位上会暴露在溶剂中，这表明减弱不需要的CYP活性的努力可以集中在这个位置上，而不会显着影响FXa的效力。对6-取代的烟酰胺基胍进行的进一步SAR研究导致发现了6-（二甲基氨基甲酰基）烟酰胍36（BMS-344577，IC 50  = 9 nM，EC 2×PT  = 2.5μM），发现具有选择性，口服有效的FXa抑制剂，在动物模型中具有出色的体外耐受性，良好的药代动力学和药效学。