N′-((4-chlorophenyl)carbamothioyl)-N,N-diethylbenzimidamide | 69818-65-1

• 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′-((4-chlorophenyl)carbamothioyl)-N,N-diethylbenzimidamide
• 英文别名: N'-[(4-chloro-phenyl)-thiocarbamoyl]-N,N-diethyl-benzamidine；1-(4-Chlorophenyl)-3-[diethylamino(phenyl)methylidene]thiourea；1-(4-chlorophenyl)-3-[diethylamino(phenyl)methylidene]thiourea
• CAS: 69818-65-1
• 化学式: C₁₈H₂₀ClN₃S
• 分子量: 345.896
• InChiKey: RASZLOBOKUIEQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  59.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N′-((4-chlorophenyl)carbamothioyl)-N,N-diethylbenzimidamide 以 四氢呋喃 、 乙腈 为溶剂， 生成 5-(2-((4-chlorophenyl)amino)-4-phenylthiazol-5-yl)-6H-1,3,4-thiadiazin-2-amine
  参考文献：
  名称：

  Thiazolyl-thiadiazines as Beta Site Amyloid Precursor Protein Cleaving Enzyme-1 (BACE-1) Inhibitors and Anti-inflammatory Agents: Multitarget-Directed Ligands for the Efficient Management of Alzheimer’s Disease

  摘要：

  Alzheimer's disease (AD) is associated with multiple neuropathological events including beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibition and neuronal inflammation, ensuing degeneracy, and death to neuronal cells. Targeting such a complex disease via a single target directed treatment was found to be inefficacious. Hence, with an intention to incorporate multiple therapeutic effects within a single molecule, multitarget-directed ligands (MTDLs) have been evolved. Herein, for the first time, we report the discovery of novel thiazolyl-thiadiazines that can serve as MTDLs as evident from the in vitro and in vivo studies. These MTDLs exhibited BACE-1 inhibition down to micromolar range, and results from the in vivo studies demonstrated efficient anti-inflammatory activity with inherent gastrointestinal safety. Moreover, compound 6d unveiled noteworthy antioxidant, antiamyloid, neuroprotective, and antiamnesic properties. Overall, results of the present study manifest the potential outcome of thiazolyl-thiadiazines for AD treatment.

  DOI：

  10.1021/acschemneuro.8b00063
• 作为产物：
  描述：

  苯甲腈 在 aluminum (III) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 N′-((4-chlorophenyl)carbamothioyl)-N,N-diethylbenzimidamide
  参考文献：
  名称：

  A Diversified Assembly of 1,2,4-Oxadiazol-3-amines: Metallic Thiophile Catalyzed Chemoselective One-Pot Reaction of Aryl Isothiocyanates, Amidines/Guanidines, and Hydroxylamine

  摘要：

  An efficient one-pot synthesis of 1,2,4-oxadiazol-3-amines from simple starting materials, isothiocyanates, amidines/guanidines, and hydroxylamine, is described. The reaction is facilitated by metallic-thiophile-assisted desulfurization of in situ formed amidino- or guanidinothiourea to give chemoselectively N-hydroxyguanidine intermediates that give exclusively various 1,2,4-oxadiazol-3-amines in good to excellent yields. The reaction mechanistic pathway may proceed through an intramolecular 5-exotrig cyclization.

  DOI：

  10.1055/s-0032-1317504

文献信息

• (3+2) Annulation of Amidinothioureas with Binucleophile: Synthesis and Antimicrobial Activity of 3-Phenylamino-5-aryl/alkyl-1,2,4-oxadiazole Derivatives
  作者：Swapnil G. Yerande、Amruta B. Ghaisas、Kiran M. Newase、Wei Wang、Kan Wang、Alexander Dömling

  DOI：10.1002/jhet.1873

  日期：2014.11

  efficient method for preparation of 3‐phenylamino‐5‐aryl/alkyl‐1,2,4‐oxadiazole by (3+2) annulation of amidinothioureas with binucleophilic hydroxylamine hydrochloride in the presence of mercury (II) chloride. Desired 3‐phenylamino‐5‐aryl/alkyl‐1,2,4‐oxadiazole was prepared in good to moderate yields. On the basis of the literature precedence, the mechanism for the formation of 3‐phenylamino‐5‐aryl/alkyl‐1

  在本文中，我们报告了在氯化汞（II）存在下，通过（3 + 2）氨基硫脲与双亲核羟胺盐酸盐环化（3 + 2）制备3-苯基氨基-5-芳基/烷基1,2,4-恶二唑的有效方法。所需的3-苯基氨基-5-芳基/烷基1,2,4-恶二唑的制备得率中等至中等。根据文献的优先次序，提出了3-苯基氨基-5-芳基/烷基1,2,4-恶二唑的形成机理。测试了合成的化合物的抗菌活性，并显示出对革兰氏阳性细菌（金黄色葡萄球菌）和真菌（白色念珠菌）的抑制作用。
• Mercury(II) Chloride-Mediated Desulphurization of Amidinothioureas: Synthesis and Antimicrobial Activity of 3-Amino-1,2,4-triazole Derivatives
  作者：Swapnil G. Yerande、Chetna D. Baviskar、Kiran M. Newase、Wei Wang、Kan Wang、Alexander Dömling

  DOI：10.1002/jhet.1890

  日期：2014.11

  The synthesis of 3‐amino‐1,2,4‐triazole via mercury(II) chloride‐mediated cyclization of amidinothiourea is described. This procedure offers a general and efficient route to synthesize the title compound by 3 + 2 annulation reaction. On the basis of the literature precedence, the mechanism for the formation of 3‐amino‐1,2,4‐triazole is proposed. When the synthesized compounds were tested for their

  描述了通过氯化汞（II）介导的thio硫脲的环化反应，合成3-氨基1,2,4-三唑。该程序提供了通过3 + 2环化反应合成标题化合物的一般有效途径。根据文献的优先次序，提出了3-氨基1,2,4-三唑的形成机理。当测试合成的化合物的抗微生物活性时，对被测试的微生物显示出有希望的抑制作用。
• Design, computational studies, synthesis and biological evaluation of thiazole-based molecules as anticancer agents
  作者：Anuradha、Sagarkumar Patel、Rajkumar Patle、Preethi Parameswaran、Alok Jain、Amit Shard

  DOI：10.1016/j.ejps.2019.04.005

  日期：2019.6

  significantly altered in several tumor types which position them as striking targets for therapeutic intervention. Here we designed, computationally evaluated, synthesized, and biologically tested structurally optimized thiazole-based small molecules as anticancer agents. Methods The virtually designed 200 molecules were subjected to rigorous docking and in silico ADME-Toxicity studies. Out of this, 23 skeletally

  背景 消除癌症保证了针对特定途径的有效治疗方式，这些途径在肿瘤增殖和存活中失调。抗凋亡的Bcl-2蛋白在几种肿瘤类型中发生了显着变化，将其定位为治疗干预的靶标。在这里，我们设计，计算评估，合成和生物学测试了结构优化的基于噻唑的小分子作为抗癌剂。 方法 虚拟设计的200个分子经过了严格的对接和计算机模拟ADME毒性研究。其中，使用便宜且容易获得的试剂分三步合成了23个通过泛分析干扰化合物（PAINS）过滤器并在合成上可行的基于骨架的噻唑类分子。分子是在体外针对Bcl-2的-的Jurkat，A-431癌细胞系和ARPE-19细胞系进行评估。进行了分子动力学（MD）模拟研究，以分析Bcl-2中配体32诱导的构象变化。对化合物32处理的Bcl-2细胞进行流式细胞术分析以检查细胞凋亡。 结果 该分子表现出与Bcl-2的明显相互作用，并具有可接受的药物样性质，如在计算机中测试的。多步合成以高达80％的
• Rajappa,S.; Sreenivasan,R., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1978, vol. 16, p. 749 - 751
  作者：Rajappa,S.、Sreenivasan,R.

  DOI：——

  日期：——
• Design, synthesis and characterization of novel 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives as inhibitors of NF-κB and AP-1 mediated transcription activation and as potential anti-inflammatory agents
  作者：Rajan S. Giri、Hardik M. Thaker、Tony Giordano、Jill Williams、Donna Rogers、Vasudevan Sudersanam、Kamala K. Vasu

  DOI：10.1016/j.ejmech.2008.10.031

  日期：2009.5

  A series of 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives were designed and synthesized. Synthesized molecules were further evaluated for their inhibitory activity towards transcription factors NF-kappa B and AP-1 mediated transcriptional activation in a cell line based in vitro as well as for their anti-inflammatory activity in in vivo model of acute inflammation. This series provides us with selective and dual inhibitors of NF-kappa B and AP-1 mediated transcriptional activation which also exhibit significant efficacy in in vivo model of inflammation. Two of the compounds 9m and 9o turned out to be the most promising dual inhibitors of NF-kappa B and AP-1 mediated transcriptional activation with an IC50 of 3.3 mu M for both. 9n (IC50 = 5.5 mu M) and 9p (IC50 = 5.5 mu M) emerged as selective inhibitors of NF-kappa B mediated transcriptional activation and 9c (IC50 = 5.5 mu M) and 9d (IC50 = 5.5 mu M) were found to be more selective inhibitor of AP-1 mediated transcriptional activity. Though the relationship between the activities shown by these compounds in in vivo and in vitro model is still to be established, these results suggest the suitability of the designed molecular framework as a potential anti-inflammatory molecular framework which also exhibits the inhibitory activity towards NF-kappa B and AP-1 mediated transcriptional activation. This will be worth studying further to explore its complete potential particularly in chronic inflammatory conditions. The structure activity relationship (SAR) of this series has been discussed herein. (C) 2008 Elsevier Masson SAS. All rights reserved.