N-(4-nitrobenzoyl)thiourea | 38749-68-7

• 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-(4-nitrobenzoyl)thiourea
• 英文别名: N-p-Nitrobenzoyl-thioharnstoff；(4-nitro-benzoyl)-thiourea；(4-Nitro-benzoyl)-thioharnstoff；N-carbamothioyl-4-nitrobenzamide
• CAS: 38749-68-7
• 化学式: C₈H₇N₃O₃S
• 分子量: 225.228
• InChiKey: XNRQGTGHSTWESL-UHFFFAOYSA-N

物化性质

• 熔点：
  201-203 °C
• 密度：
  1.498±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 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：
  133
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-nitrobenzoyl)thiourea 在 盐酸 作用下， 以 水 、 丙酮 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  鉴定新型硫脲-二苯乙烯-三嗪共轭物作为有说服力的淋巴样酪氨酸磷酸酶抑制剂

  摘要：

  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。

  DOI：

  10.1002/jhet.4060
• 作为产物：
  描述：

  对硝基苯甲酰异硫氰酸盐 在 氨 作用下， 以 二氯甲烷 为溶剂， 生成 N-(4-nitrobenzoyl)thiourea
  参考文献：
  名称：

  4′-Methyl-4,5′-bithiazole-based correctors of defective ΔF508-CFTR cellular processing

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2008.03.037

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.
• Risk-resistance adaptation model for caregivers and their children with sickle cell syndromes
  作者：Ronald T. Brown、Richard Lambert、Danielle Devine、Kevin Baldwin、Robert Casey、Karla Doepke、Carolyn E. Ievers、Lewis Hsu、Iris Buchanan、James Eckman

  DOI：10.1007/bf02895780

  日期：2000.6

  This investigation examined the risk-resistance adaptation model for children with sickle cell disease and their primary caregivers. Participants were 55 children, ranging in age from 5 to 16 years with a mean age of 9 years 2 months, diagnosed with sickle cell disease and their primary caregivers, recruited from a university medical center Measures included adjustment (i.e. primary caregiver and child adjustment), risk factors (i.e. disease and disability, functional independence, and psychosocial stressors), resistance factors (i.e, intrapersonal health locus of control, social-ecological), and stress processing (coping). Primary caregivers' adjustment was associated with developmental coping, R-change(2) = .08, and child adaptation was associated with an internal health locus of control, R-change(2) = .22. An indirect effect of primary caregivers' coping on child adjustment was found through influence on primary caregivers' adjustment, R-change(2) = .11. The findings support research among other chronically ill populations that suggests an association between coping and disease adjustment. The results were interpreted to support the use of theoretically driven models in predicting the adaptation of children with chronic illness and adjustment in their caregivers.
• 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：——
• A Facile Synthesis of Substituted <i>N</i>-Benzoylthiourea
  作者：Xiaoyong Xu、Zhongli、Zhengyu Yang、Gang Chen、Xuhong Qian

  DOI：10.1081/scc-120021977

  日期：2003.1.8

  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.