N-carbamothioyl-4-methoxybenzamide | 36145-58-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-carbamothioyl-4-methoxybenzamide
• CAS: 36145-58-1
• 化学式: C₉H₁₀N₂O₂S
• 分子量: 210.257
• InChiKey: KATYPQWDPOAQOC-UHFFFAOYSA-N

物化性质

• 熔点：
  202-204 °C(Solv: ethanol (64-17-5))
• 密度：
  1.294±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  96.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-carbamothioyl-4-methoxybenzamide 在 1-氧杂-2-氮杂螺[2.5]辛烷 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以79%的产率得到4-甲氧基苯甲酰胺
  参考文献：
  名称：

  Andreae, Siegfried; Schmitz, Ernst, Journal fur praktische Chemie (Leipzig 1954), 1987, vol. 329, # 6, p. 1008 - 1014

  摘要：

  DOI：
• 作为产物：
  描述：

  4-甲氧基苯甲酰异硫氰酸酯 在 三羟甲基氨基甲烷 作用下， 以 二氯甲烷 为溶剂， 以15.8%的产率得到N-carbamothioyl-4-methoxybenzamide
  参考文献：
  名称：

  A Facile Synthesis of Substituted N-Benzoylthiourea

  摘要：

  One pot reaction of benzoyl isothiocyanate and Tris(hydroxymethyl)aminomethane (Tris) at room temperature with polyethylene glycol-400 (PEG-400) as solid-liquid phase-transfer catalyst produced substituted N-benzoylthioureas with high yield. A reasonable pathway for their formation has been suggested.

  DOI：

  10.1081/scc-120021977

文献信息

• Synthesis and Structure-Activity Relationship Studies of <i>N</i>-monosubstituted Aroylthioureas as Urease Inhibitors
  作者：Wei-Wei Ni、Hai-Lian Fang、Ya-Xi Ye、Wei-Yi Li、Li Liu、Zi-Juan Fu、Dawalamu、Wen-Yan Zhu、Ke Li、Fang Li、Xia Zou、Hui Ouyang、Zhu-Ping Xiao、Hai-Liang Zhu

  DOI：10.2174/1573406416999200818152440

  日期：2021.11

  Thiourea is a classical urease inhibitor which is usually used as a positive control, and many N,N'-disubstituted thioureas have been determined as urease inhibitors. However, due to steric hindrance, N,N'-disubstituted thiourea motif could not bind urease as thiourea. On the contrary, N-monosubstituted thiourea with a tiny thiourea motif could theoretically bind into the active pocket as thiourea.

  A series of N-monosubstituted aroylthioureas were designed and synthesized for evaluation as urease inhibitors.

  Urease inhibition was determined by the indophenol method and IC₅₀ values were calculated using computerized linear regression analysis of quantal log dose-probit functions. The kinetic parameters were estimated via surface plasmon resonance (SPR) and by nonlinear regression analysis based on the mixed type inhibition model derived from Michaelis-Menten kinetics.

  Compounds b2, b11, and b19 reversibly inhibited urease with a mixed mechanism, and showed excellent potency against both cell-free urease and urease in the intact cell, with IC₅₀ values being 90- to 450-fold and 5- to 50-fold lower than the positive control acetohydroxamic acid, respectively. The most potent compound b11 showed an IC₅₀ value of 0.060 ± 0.004μM against cell-free urease, which bound to urea binding site with a very low KD value (0.420±0.003nM) and a very long residence time (6.7 min). Compound b11 was also demonstrated to have very low cytotoxicity to mammalian cells.

  The results revealed that N-monosubstituted aroylthioureas bound to the active site of urease as expected, and represent a new class of urease inhibitors for the development of potential therapeutics against infections caused by urease-containing pathogens.

  背景： 硫脲是一种经典的尿素酶抑制剂，通常用作阳性对照，许多N,N'-二取代硫脲已被确定为尿素酶抑制剂。然而，由于空间位阻，N,N'-二取代硫脲基团无法像硫脲那样结合尿素酶。相反，具有微小硫脲基团的N-单取代硫脲理论上可以像硫脲一样结合到活性口袋中。 目标： 设计并合成了一系列N-单取代芳酰硫脲，用于评估其作为尿素酶抑制剂的效果。 方法： 通过吲哚酚法确定尿素酶抑制作用，并利用量化对数剂量-概率函数的计算机化线性回归分析计算IC50值。通过表面等离子共振（SPR）和基于从迈克尔斯-门特金动力学导出的混合型抑制模型的非线性回归分析估计动力学参数。 结果： 化合物b2、b11和b19以混合机制可逆地抑制尿素酶，并对无细胞尿素酶和完整细胞中的尿素酶表现出极佳的效力，其IC50值分别比阳性对照乙酰羟羟肟酸低90至450倍和5至50倍。最有效的化合物b11对无细胞尿素酶显示出IC50值为0.060 ± 0.004μM，其与尿素结合位点的结合具有非常低的KD值（0.420±0.003nM）和非常长的停留时间（6.7分钟）。化合物b11还被证明对哺乳动物细胞具有非常低的细胞毒性。 结论： 结果表明，N-单取代芳酰硫脲如预期地结合到尿素酶的活性位点，并代表了一类新的尿素酶抑制剂，可用于开发针对含尿素酶病原体引起的感染的潜在治疗药物。
• Stereoselective or Exclusive Synthesis of Ethyl (Z)-2-(2-Substituted-thiazol-4-yl)pent-2-enoates from Ethyl (E/Z)-2-(2-Bromoacetyl)pent-2-enoate
  作者：Ya-Fei Ji、Jiao-Jiao Zhai、Jian-An Jiang、Shun-Li Zhang、Cheng Chen、Hong-Wei Liu、Dao-Hua Liao

  DOI：10.1055/s-0033-1338954

  日期：——

  cis-configuration formation, and opportunely blocking a potential E/Z isomerization. The practical applicability was highlighted by the synthesis of (Z)-2-(2-tert-butoxycarbonylaminothiazol-4-yl)pent-2-enoic acid, a commercially important side-chain material of cefcapene pivoxil, in a two-step procedure.

  从 (E/Z)-2-(2-溴乙酰基)pent-2 乙基 (E/Z)-2-(2-溴乙酰基)pent-2 制备一系列 (Z)-2-(2-取代-噻唑-4-基)pent-2-enoates 的立体选择性或排他性方法-烯酸酯和硫脲或硫代酰胺的产率很高。这种方法涉及季碳立体控制的顺式构型形成，并适时地阻止潜在的 E/Z 异构化。(Z)-2-(2-tert-butoxycarbonylaminothiazol-4-yl)pent-2-enoic acid，一种商业上重要的cefcapene pivoxil侧链材料，通过两步法合成，突出了实际适用性.
• Identification of novel thiourea‐stilbene‐triazine conjugates as persuasive lymphoid tyrosine phosphatase inhibitors
  作者：Iram Batool、Farukh Jabeen、Nadeem Ahmed Vellore、Ghulam Shabir、Aamer Saeed

  DOI：10.1002/jhet.4060

  日期：——

  A library of novel thiourea‐based symmetrical stilbene‐triazines (5a‐i) was synthesized in an effort to develop new protein tyrosine phosphatase LYP inhibitors. The versatile nature of 2,4,6‐trichloro‐1,3,5‐triazine allows considerable scope for derivatization and hence exploration of structure activity relationships. A convenient and versatile three‐step synthetic approach involved the successive

  为了开发新的蛋白质酪氨酸磷酸酶LYP抑制剂，合成了一个基于硫脲的对称二苯乙烯-三嗪新化合物（5a-i）库。2,4,6-三氯-1,3,5-三嗪的通用性质为衍生化提供了广阔的空间，因此也探索了结构活性关系。一种方便且通用的三步合成方法涉及用各种取代基连续取代2,4,6-三氯-1,3,5-三嗪的两个氯基，以进行结构修饰。对新合成的衍生物进行酪氨酸磷酸酶LYP抑制研究。化合物5k和5l的鉴定为体外生物测定的结果带来了希望在苯环上具有4-甲基和4-甲氧基取代基，作为LYP抑制的铅和选择性候选物，IC 50值分别为2.1±0.05μM和28±3.3μM。此外，进行了对接研究，以确定基于硫脲的二苯乙烯-三嗪化合物与淋巴酪氨酸磷酸酶的可能相互作用位点。对接计算的结果进一步确定了化合物5k和5l的抑制潜力。结果表明，化合物5k可用作设计最有效的LYP抑制剂的结构模型。
• [EN] CELLULOSE SYNTHASE INHIBITORS AS A NEW CLASS OF HERBICIDE AND NON-GMO CROPS RESISTANT TO THE HERBICIDE<br/>[FR] INHIBITEURS DE CELLULOSES SYNTHASES UTILISÉS EN TANT QUE NOUVELLE CLASSE D'HERBICIDE ET CULTURES NON-OGM QUI SONT RÉSISTANTES À L'HERBICIDE
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2019112791A1

  公开（公告）日：2019-06-13

  Using chemical genetic screening, we discovered a small molecule Cellulosin (aka endosidin20 or ES20) that causes cell swollen and inhibits plant growth, but does not disrupt global vesicle trafficking. By doing mutant screening, we obtained multiple alleles of Arabidopsis thaliana that are resistant to Cellulosin inhibition in growth. Those mutated amino acid residues are conserved across plant species. Cellulosin targets a group of cellulose synthases (CesAs) of Arabidopsis thaliana by binding to a conserved domain essential for the catalytic activity of CesA. Cellulosin may target and inhibit all subtypes of CesAs in plants. The present invention relates to Cellulosin, a cellulose synthase inhibitor, its analogs or derivatives as a broad-spectrum herbicide. The mutated genes, their protein products and a cell or a plant having those mutated genes or expressing those protein products are within the scope of this disclosure.

  使用化学遗传筛选，我们发现了一种小分子Cellulosin（又名endosidin20或ES20），它会导致细胞肿胀并抑制植物生长，但不会干扰全局囊泡运输。通过突变筛选，我们获得了多个阿拉伯芥（Arabidopsis thaliana）等位基因，这些基因对Cellulosin抑制生长具有抗性。这些突变的氨基酸残基在植物物种中是保守的。Cellulosin通过结合到对CesA催化活性至关重要的保守结构域，靶向阿拉伯芥的一组纤维素合成酶（CesAs）。Cellulosin可能会靶向并抑制植物中的所有CesAs亚型。本发明涉及Cellulosin，一种纤维素合成酶抑制剂，其类似物或衍生物作为广谱除草剂。这些突变基因、它们的蛋白质产物以及具有这些突变基因或表达这些蛋白质产物的细胞或植物均在本公开范围之内。
• Catalyst-free activation of N–C(O) Amide bonds – efficient cascade synthesis of <i>N</i>-acyl thiocarbamides in batch and continuous-flow
  作者：Karthick Govindan、Nian-Qi Chen、Wei-Yu Lin

  DOI：10.1039/d4gc00518j

  日期：——

  challenge. Herein, we present a green method to activate the N–C amide bond in N-acyl saccharin, employing ammonium thiocyanate in sustainable 2-MeTHF as the solvent medium. This approach facilitates the efficient and divergent synthesis of N-carbamothioylbenzamides and O-alkyl thiocarbamides. Additionally, it features a bench-stable and recyclable core of reagents, a low E-factor, high atom efficiency

  酰胺键是化学和生物学中的重要官能团，是帮助创建重要的药物和工业化合物的各种过程的组成部分。通过无金属、环保且可持续的方法开发有效的转化来破坏酰胺中的 N-C 键，这是一个值得注意的合成挑战。在此，我们提出了一种激活N-酰基糖精中 N-C 酰胺键的绿色方法，使用可持续的 2-MeTHF 中的硫氰酸铵作为溶剂介质。该方法有利于N-硫代氨基甲酰胺和O-烷基硫代脲的高效且多样化的合成。此外，它还具有稳定且可回收的试剂核心、低E因子、高原子效率、简单温和的条件、优异的官能团耐受性和广泛的底物范围。此外，我们通过连续流动方法在很短的反应时间（17分钟）内完成了N-硫代氨基甲酰基苯甲酰胺的合成，这凸显了我们的新方法在合成和工业用途上具有通用性，并且适用于间歇和流动条件。该方法展示了克级反应的实用性，并通过成功的合成转化展示了其合成有价值的杂环化合物（如噻唑和三唑）的功效。