1-(2-chlorobenzoyl)thiourea | 6965-59-9

• 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: 1-(2-chlorobenzoyl)thiourea
• 英文别名: N-(2-chlorobenzoyl)thiourea；N-o-Chlorbenzoylthioureid；N-o-Chlorbenzoylthioharnstoff；N-(aminothioxomethyl)-2-chloro-benzamide；N-carbamothioyl-2-chlorobenzamide
• CAS: 6965-59-9
• 化学式: C₈H₇ClN₂OS
• 分子量: 214.675
• InChiKey: UROWSAGPOYOHJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 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：
  87.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(2-chlorobenzoyl)thiourea 在 硫酸 作用下， 以 水 为溶剂， 生成 2-巯基-4(3H)-喹唑酮
  参考文献：
  名称：

  Ahmed, Ejaz; Manwar, Muhammad Ramzan; Sharif, Ahsan, Journal of the Chemical Society of Pakistan, 2011, vol. 33, # 3, p. 417 - 420

  摘要：

  DOI：
• 作为产物：
  描述：

  异硫氰酸 2-氯苯甲酰脂 在 ammonium hydroxide 作用下， 反应 2.0h， 生成 1-(2-chlorobenzoyl)thiourea
  参考文献：
  名称：

  1-酰基硫脲中的分子内和分子间氢键和构象：1-（2-氯苯甲酰基）硫脲的实验和理论方法。

  摘要：

  对新的1-（2-氯苯甲酰基）硫脲物种的振动分析（FT-IR和FT-Raman）表明，强烈的分子内相互作用会影响构象性质。X射线结构测定证实了在羰基（-CO）和硫代酰胺（-NH 2）基团之间存在分子内NH ＝ OC氢键。此外，周期性系统电子密度和拓扑分析已被用来表征晶体间的分子间相互作用。硫代酰胺（NH）和尿素（NH2）基团与硫代羰基键（CS）之间扩展的NHcarbonylSC氢键网络决定了晶体堆积。自然键轨道（NBO）种群分析表明，强烈的超共轭远程相互作用是分子内和分子间相互作用的原因。

  DOI：

  10.1016/j.saa.2015.02.042

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。
• 4′-Methyl-4,5′-bithiazole-based correctors of defective ΔF508-CFTR cellular processing
  作者：Choong Leol Yoo、Gui Jun Yu、Baoxue Yang、Lori I. Robins、A.S. Verkman、Mark J. Kurth

  DOI：10.1016/j.bmcl.2008.03.037

  日期：2008.4

  The synthesis and Delta F508-CFTR corrector activity of a 148-member methylbithiazole-based library are reported. Synthetic routes were devised and optimized to generate methylbithiazole analogs in four steps. Corrector potency and efficacy were assayed using epithelial cells expressing human Delta F508-CFTR. These structure-activity data establish that the bithiazole substructure plays a critical function; eight novel methylbithiazole correctors were identified with low micromolar potencies. (c) 2008 Elsevier Ltd. All rights reserved.
• Pandeya, S. N.; Singh, B. N., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 3, p. 234 - 236
  作者：Pandeya, S. N.、Singh, B. N.

  DOI：——

  日期：——
• PANDEYA S. N.; SINGH B. N., INDIAN J. CHEM., 1980, B19, NO 3, 234-236
  作者：PANDEYA S. N.、 SINGH B. N.

  DOI：——

  日期：——
• Ahmed, Ejaz; Manwar, Muhammad Ramzan; Sharif, Ahsan, Journal of the Chemical Society of Pakistan, 2011, vol. 33, # 3, p. 417 - 420
  作者：Ahmed, Ejaz、Manwar, Muhammad Ramzan、Sharif, Ahsan、Mukhtar-Ul-Hassan、Ahmed, Neman、Malik, Abdul、Mahmood, Zaid、Munawar, Munawar Ali

  DOI：——

  日期：——