2-[(1H-benzimidazol-2-yl)sulfanyl]-1-(4-methylphenyl)ethan-1-one | 27097-09-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[(1H-benzimidazol-2-yl)sulfanyl]-1-(4-methylphenyl)ethan-1-one
• 英文别名: 2-((1H-benzo[d]imidazol-2-yl)thio)-1-(p-tolyl)ethan-1-one；2-(1H-benzo[d]imidazol-2-ylthio)-1-p-tolylethanone；2-(1H-benzoimidazol-2-ylsulfanyl)-1-p-tolyl-ethanone；Benzimidazolylthioacetophenon；2-(1H-benzimidazol-2-ylsulfanyl)-1-(4-methylphenyl)ethanone
• CAS: 27097-09-2
• 化学式: C₁₆H₁₄N₂OS
• 分子量: 282.366
• InChiKey: BPVRPBBHENIHEY-UHFFFAOYSA-N

物化性质

• 熔点：
  184-186 °C(Solv: ligroine (8032-32-4))
• 沸点：
  507.8±52.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(1H-benzimidazol-2-yl)sulfanyl]-1-(4-methylphenyl)ethan-1-one 在 PPA 作用下， 生成 3-(p-tolyl)benzo[4,5]imidazo[2,1-b]thiazole
  参考文献：
  名称：

  SINGH S; SINGH H; SINGH M, Indian journal of chemistry, 1970, vol. 8, # 3, p. 230 - 232

  摘要：

  DOI：
• 作为产物：
  描述：

  2-((2-oxo-2-(p-tolyl)ethyl)thio)-1H-benzo[d]imidazol-3-ium sulfate salt 以 水 为溶剂， 反应 2.0h， 生成 2-[(1H-benzimidazol-2-yl)sulfanyl]-1-(4-methylphenyl)ethan-1-one
  参考文献：
  名称：

  2-((Benzimidazol-2-yl)thio)-1-arylethan-1-ones: Synthesis, crystal study and cancer stem cells CD133 targeting potential

  摘要：

  In order to develop a potent anti-tumor agent that can target both cancer stem cells and the bulk of tumor cells, a series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a-o was synthesized. All compounds were evaluated for their anti-proliferative activity towards colon HT-29 cancer cell line. In addition, their inhibitory effect against cell surface expression of CD133, a potent cancer stem cells (CSCs) marker, in the same cells was evaluated by flow cytometry at 10 mu M. Compound 51 emerged as the most active anti-proliferative analog against HT-29 (IC50 = 18.83 +/- 1.37 mu M), that almost equipotent as 5-fluorouracil (IC50 = 15.83 +/- 1.63 mu M) with 50.11 +/- 4.05% inhibition effect on CD133 expression, suggested dual targeted effect. Also, compounds 5h, 5j, 5k and 5m-o inhibited the expression of CD133 with more than 50%. The SAR study pointed out the significance of substitution of the pendent phenyl group with lipophilic electron-donating groups or replacing it by 2-thienyl or 2-furyl groups. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.023

文献信息

• Inhibitors of Apoptosis in Lymphocytes:  Synthesis and Biological Evaluation of Compounds Related to Pifithrin-α
  作者：Sylvie D. Barchéchath、Rommel I. Tawatao、Maripat Corr、Dennis A. Carson、Howard B. Cottam

  DOI：10.1021/jm0502034

  日期：2005.10.1

  39 were more protective than 39, while the aromatic analogues of 1 were not active. Compound 19 containing a pyrrolidinyl substituent on the phenyl ring provided potent antiapoptotic activity (EC50 of 1.31 microM compared to 4.16 microM for 1). Modification of aromatic 39 with a pyrrolidinyl para substituent (compound 60) enhanced the activity, lowering the EC50 to 0.35 microM. Also, 60 provided significant

  化学性保护细胞免受毒素或电离辐射诱导的细胞凋亡可能对生物防御和急性损伤的治疗很重要。我们描述了一系列小的杂环，包括稠合的苯并噻唑，苯并咪唑和相关化合物，它们消除了地塞米松和γ射线诱导的胸腺细胞凋亡。为了优化以前报道的pifithrin-alpha（PFT-alpha，1）的保护活性，合成了该衍生物和相应的闭环咪唑并苯并噻唑（IBT，39）的各种衍生物和类似物。39的芳香族类似物比39更具保护性，而1的芳香族类似物则没有活性。在苯环上包含吡咯烷基取代基的化合物19提供了有效的抗凋亡活性（EC50为1.31 microM，而4的EC16为4.16 microM）。用吡咯烷基对位取代基（化合物60）修饰芳香族化合物39可增强活性，将EC50降低至0.35 microM。同样，60预期也提供了有效的保护，以抵抗伽马射线辐射诱导的细胞凋亡。化合物19和60对于潜在的临床开发可能很有希望。
• Synthesis of difluorinated β-ketosulfones and novel gem-difluoromethylsulfone-containing heterocycles as fluorinated building blocks
  作者：Hossein Loghmani-Khouzani、Dariush Hajiheidari

  DOI：10.1016/j.jfluchem.2009.12.022

  日期：2010.5

  A series of new heterocyclic β-ketosulfides was prepared by the reaction of the corresponding heterocyclic thiols with α-bromoacetophenone and its derivatives. Oxidation of the products using m-CPBA gave the corresponding heterocyclic β-ketosulfones, which, on treatment with Selectfluor™ under anhydrous condition underwent electrophilic fluorination resulting in new heterocycles with difluoromethylene

  通过相应的杂环硫醇与α-溴苯乙酮及其衍生物的反应，制备了一系列新的杂环β-酮硫醚。使用产品的氧化米-CPBA得到相应的杂环β-酮砜，其中，无水条件下使用的Selectfluor™治疗经历导致与相邻的硫原子和羰基二氟亚甲基部分的新的杂环电氟化。以不同的杂环部分作为模型化合物，对五种类型的所得产物进行碱基诱导的裂解，得到与相应杂环连接的二氟甲基砜。它们可以被认为是用于进一步阐述的有趣的氟化构建基块。
• A New Aspect of the Pfitzinger Reaction: Microwave-assisted Synthesis of the New Heterocyclic Ring System 6-Arylbenzo[4,5]imidazolo[2,1-b]quino[4,3-e]-1,3-thiazin-14-one
  作者：Hatem A. Abdel-Aziz、Sobhi M. Gomha

  DOI：10.1515/znb-2009-0709

  日期：2009.7.1

  We report herein on the utility of the Pfitzinger reaction in a facile two-step synthesis of the new heterocyclic ring system 6-arylbenzo[4,5]imidazolo[2,1-b]quino[4,3-e]-1,3-thiazin-14-one using microwave irradiation (MWI) and/or conventional heating. Microwave irradiation was used for a rapid and efficient synthesis of quinoline-4-carboxylic acids 6a - d from the reaction of isatin with 2-(1Hbenzimidazol- 2-ylthio)-1-arylethanones 3a - d. Cyclization of cinchoninic acids 6a - d afforded the fused title compounds 7a - d.

  我们在此报告了Pfitzinger反应在新的杂环环系统6-芳基苯并[4,5]咪唑并[2,1-b]喹诺[4,3-e]-1,3-噻唑-14-酮的简便两步合成中的实用性，使用微波辐射（MWI）和/或常规加热。微波辐射用于通过异喹啉与2-(1H苯并咪唑-2-基硫基)-1-芳基乙酮酮的反应快速高效地合成喹啉-4-羧酸6a-d。6a-d的辛克酸环化形成了融合的标题化合物7a-d。
• Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents
  作者：Hatem Abdel-Aziz、Wagdy Eldehna、Hazem Ghabbour、Ghada Al-Ansary、Areej Assaf、Abdullah Al-Dhfyan

  DOI：10.3390/ijms17081221

  日期：——

  On account of its poor prognosis and deficiency of therapeutic stratifications, triple negative breast cancer continues to form the causative platform of an incommensurate number of breast cancer deaths. Aiming at the development of potent anticancer agents as a continuum of our previous efforts, a novel series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a–w was synthesized and evaluated for its anti-proliferative activity towards triple negative breast cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against MDA-MB-468 (IC50 = 19.90 ± 1.37 µM), with 2.1-fold increased activity compared to 5-fluorouracil (IC50 = 41.26 ± 3.77 µM). Compound 5k was able to induce apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of florecsein isothiocyanate annexin V (Annexin V–FITC)-positive apoptotic cells (upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control accompanied by significant increase in the proportion of cells at pre-G1 (the first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a quantitative structure activity relationship (QSAR) model was established to investigate the structural requirements orchestrating the anti-proliferative activity. Finally, we established a theoretical kinetic study.

  由于其预后不良和治疗分层的不足，三阴性乳腺癌继续成为导致乳腺癌死亡人数不相称的原因平台。作为我们之前努力的连续体，旨在开发有效的抗癌药物，合成了一系列新型 2-((benzimidazol-2-yl)thio)-1-aryllethan-1-ones 5a–w 并评估了其抗癌效果。 -对三阴性乳腺癌（TNBC）MDA-MB-468细胞的增殖活性。化合物 5k 是 MDA-MB-468 活性最强的类似物 (IC50 = 19.90 ± 1.37 µM)，与 5-氟尿嘧啶相比，活性增加了 2.1 倍 (IC50 = 41.26 ± 3.77 µM)。化合物 5k 能够诱导 MDA-MB-468 细胞凋亡，异硫氰酸荧光素膜联蛋白 V (Annexin V–FITC) 阳性凋亡细胞的百分比显着增加（右上 (UR) + 右下 (LR)） ）与对照相比增加了 2.8 倍，同时在细胞周期分析中，G1 前（第一个间隙期）的细胞比例显着增加了 8.13 倍。此外，还建立了定量结构活性关系（QSAR）模型来研究协调抗增殖活性的结构要求。最后，我们建立了理论动力学研究。
• A convenient one-pot synthesis of 2-benzimidazolyl-thioacetophenones and thiazolo[3,2-a]benzimidazoles
  作者：Abd El-Wareth A.O. Sarhan、Hasan A.H. El-Sherief、Abdalla M. Mahmoud

  DOI：10.1016/0040-4020(96)00569-8

  日期：1996.7

  etophenones 3a-d. Which on cyclization yield thiazolo[3,2-a]-benzimidazoles 4a-d. Acetylation of 3a,d gave the N-acetyl derivatives 5a,d. Cyclization of 3a-d or 5d in acetic anhydride or acetic anhydride / pyridine mixture afforded 6a-d. While reaction of 1 with aliphatic or alicyclic ketones gave directly 2,3-disubstituted thiazolo[3,2-a]benzimidazoles 7a-f and 8a-d respectively.

  2-巯基苯并咪唑（1）与芳族酮2a-d在酸化的乙酸中反应，得到2-苯并咪唑基硫代乙酰基苯乙酮3a-d。在环化反应中产生噻唑并[3，2-a]-苯并咪唑4a-d。3a，d的乙酰化得到N-乙酰基衍生物5a，d。3a-d或5d在乙酸酐或乙酸酐/吡啶混合物中的环化得到6a-d。当1与脂族或脂环族酮反应时，分别直接直接得到2，3-二取代的噻唑并[3，2-a]苯并咪唑7a-f和8a-d。