2-chloro-N-{[4-(trifluoromethyl)phenyl]methyl}acetamide | 101824-33-3

• 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: 2-chloro-N-{[4-(trifluoromethyl)phenyl]methyl}acetamide
• 英文别名: 2-Chloro-n-[4-(trifluoromethyl)benzyl]acetamide；2-chloro-N-[[4-(trifluoromethyl)phenyl]methyl]acetamide
• CAS: 101824-33-3
• 化学式: C₁₀H₉ClF₃NO
• 分子量: 251.636
• InChiKey: GPJZGQHIIRBYHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-{[4-(trifluoromethyl)phenyl]methyl}acetamide 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 14.0h， 生成 5-((1H-indol-3-yl)methylene)-2-((4-(trifluoromethyl)benzyl)imino)thiazolidin-4-one
  参考文献：
  名称：

  Discovery of certain benzyl/phenethyl thiazolidinone-indole hybrids as potential anti-proliferative agents: Synthesis, molecular modeling and tubulin polymerization inhibition study

  摘要：

  A series of certain benzyl/phenethyl thiazolidinone-indole hybrids were synthesized for the study of anti-proliferative activity against A549, NCI-H460 (lung cancer), MDA-MB-231 (breast cancer), HCT-29 and HCT-15 (colon cancer) cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). We found that compound G37 displayed highest cytotoxicity with IC50 value of 0.92 +/- 0.12 mu M towards HCT-15 cancer cell line among all the synthesized compounds. Moreover, compound G37 was also tested on normal human lung epithelial cells (L132) and was found to be safe in contrast to HCT-15 cells. The lead compound G37 showed significant G2/M phase arrest in HCT-15 cells. Additionally, compound G37 significantly inhibited tubulin polymerization with IC50, value of 2.92 +/- 0.23 mu M. Mechanistic studies such as acridine orange/ethidium bromide (AO/EB) dual staining, DAPI nuclear staining, annexinV/propidium iodide dual staining, donogenic growth inhibition assays inferred that compound G37 induced apoptotic cell death in HCT-15 cells. Moreover, loss of mitochondrial membrane potential with elevated intracellular ROS levels was observed by compound G37. These compounds bind at the active pocket of the alpha/beta-tubulin with higher number of stable hydrogen bonds, hydrophobic and arene-cation interactions confirmed by molecular modeling studies.

  DOI：

  10.1016/j.bioorg.2019.103188
• 作为产物：
  描述：

  4-(三氟甲基)苄胺 、 氯乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 生成 2-chloro-N-{[4-(trifluoromethyl)phenyl]methyl}acetamide
  参考文献：
  名称：

  骨髓嗜生态病毒整合位点 1 抑制剂的先导优化和构效关系研究

  摘要：

  我们之前的研究结果报道了骨髓嗜嗜性病毒整合位点 1 (MEIS1) 转录因子在心脏再生和造血干细胞 (HSC) 调节中的关键作用。MEIS1 作为药理抑制背景下的一个有希望的靶点，我们鉴定了一种有效的髓系亲嗜性病毒整合位点 (MEIS) 抑制剂 MEISi-1，可在体外和体内诱导小鼠和人类 HSC 扩增。在这项工作中，我们通过合成 45 种新型类似物对 MEISi-1 进行了先导优化。构效关系研究揭示了环A上的对甲氧基和环B间位的疏水部分的重要性. 获得的生物学数据得到了抑制剂对接和分子动力学模拟研究的支持。11 种化合物被描述为强效抑制剂，证明对 MEIS1 和靶基因Meis1、Hif-1 α 和p21具有更好的抑制作用。其中，4h、4f和4b是最有效的抑制剂。预测的药代动力学特性满足药物相似性标准。此外，化合物对人皮肤成纤维细胞既没有细胞毒性，也没有致突变性。

  DOI：

  10.1021/acs.jmedchem.1c00972

文献信息

• Novel 3-Nitro-1<i>H</i>-1,2,4-triazole-Based Amides and Sulfonamides as Potential Antitrypanosomal Agents
  作者：Maria V. Papadopoulou、William D. Bloomer、Howard S. Rosenzweig、Eric Chatelain、Marcel Kaiser、Shane R. Wilkinson、Caroline McKenzie、Jean-Robert Ioset

  DOI：10.1021/jm300508n

  日期：2012.6.14

  A series of novel 3-nitro-1H-1,2,4-triazole-based (and in some cases 2-nitro-1H-imidazole-based) amides and sulfonamides were characterized for their in vitro antitrypanosomal and antileishmanial activities as well as mammalian toxicity. Out of 36 compounds tested, 29 (mostly 3-nitro-1H-1,2,4-triazoles) displayed significant activity against Trypanosoma cruzi intracellular amastigotes (IC50 ranging

  一系列新型 3-硝基-1 H -1,2,4-三唑基（在某些情况下是 2-硝基-1 H-咪唑基）酰胺和磺胺类药物的体外抗锥虫和抗利什曼原虫活性被表征为以及哺乳动物毒性。在测试的 36 种化合物中，29 种（主要是 3-nitro-1 H -1,2,4-三唑）对克氏锥虫细胞内无鞭毛体（IC 50范围为 28 nM 至 3.72 μM）显示出显着的活性，而对 L6 宿主细胞没有伴随的毒性（选择性 66–2782）。在平行测试中，这些活性化合物中有 23 种比参考药物苯并硝唑更有效（高达 58 倍）。此外，九种具有中等活性的硝基三唑 (0.5 μM ≤ IC 50< 6.0 μM) 对抗布氏罗得西亚锥虫类鞭毛体的活性高 5-31 倍，对抗血流形式的布氏锥虫类鞭毛体，其被设计为过表达减少的烟酰胺腺嘌呤二核苷酸依赖性硝基还原酶。最后，三种硝基三唑对杜氏利什曼原虫的无菌形式显示出中等活性。因此，基于 3-nitro-1
• Synthesis and Characterization of Novel<i>N</i>-(Phenyl, Benzyl, Hetaryl)-2-([1,2,4]Triazolo[1,5-<i>c</i>]Quinazolin-2-ylthio)Acetamides by Spectral Data, Antimicrobial Activity, Molecular Docking and QSAR Studies
  作者：Lyudmyla M. Antypenko、Sergiy I. Kovalenko、Tetyana S. Los'、Oksana L. Rebec'

  DOI：10.1002/jhet.2702

  日期：2017.3

  Candida albicans. N‐(4‐Fluorophenyl)‐2‐([1,2,4]triazolo[1,5‐c]quinazolin‐2‐ylthio)acetamide 3e had the best minimum inhibition zones against S. aureus and E. faecalis and 3‐[([1,2,4]triazolo[1,5‐c]quinazolin‐2‐ylthio)acetyl]amino}benzoic acid 3k – against E. coli, still in lower concentration, than references. By the means of in silico molecular docking into the active sites of E. faecalis dihydrofolate

  持久的新颖有效的抗微生物剂进行搜索，ñ - （苯基，苄基，杂芳基）-2 - （[1,2,4]三唑并[1,5- c ^ ]喹唑啉-2-基硫基）的合成乙酰胺，评价了结构（ LC-MS，IR，1 H-NMR谱和元素分析），并研究针对的抗菌活性的金黄色葡萄球菌，粪肠球菌，产气肠杆菌，阪坂崎，绿脓杆菌，大肠杆菌，和肺炎克雷伯氏菌，和抗真菌-反对白色念珠菌。N-（4-氟苯基）-2-（[[1,2,4]三唑[1,5-c ]喹唑啉-2-基硫基）乙酰胺3e对S的最小抑制区最好。 金黄色葡萄球菌和Ë。 粪肠球菌和3 - [（[1,2,4]三唑并[1,5- c ^ ]喹唑啉-2-基硫基）乙酰基]氨基}苯甲酸3K -反对ë。 大肠杆菌的浓度仍低于参考文献。通过计算机分子对接到E的活性位点。 粪便二氢叶酸还原酶和阴沟肠杆菌MyrA，建议可能的活动机制。计算了抗菌活性预测的定量构效关系模型。
• Mittel zum Schützen von Kulturpflanzen vor der phytotoxischen Wirkung von herbizid wirksamen Chloracetaniliden
  申请人：CIBA-GEIGY AG

  公开号：EP0163607B1

  公开（公告）日：1989-11-08
• Lead Optimization and Structure–Activity Relationship Studies on Myeloid Ecotropic Viral Integration Site 1 Inhibitor
  作者：Bengisu Turgutalp、Merve Uslu、Sinem Helvacioglu、Mohammad Charehsaz、Enise Ece Gurdal、Wolfgang Sippl、Fatih Kocabas、Mine Yarim

  DOI：10.1021/acs.jmedchem.1c00972

  日期：2021.10.14

  site (MEIS) inhibitor, MEISi-1, to induce murine and human HSC expansion ex vivo and in vivo. In this work, we performed lead optimization on MEISi-1 by synthesizing 45 novel analogues. Structure–activity relationship studies revealed the significance of a para-methoxy group on ring A and a hydrophobic moiety at the meta position of ring B. Obtained biological data were supported by inhibitor docking and

  我们之前的研究结果报道了骨髓嗜嗜性病毒整合位点 1 (MEIS1) 转录因子在心脏再生和造血干细胞 (HSC) 调节中的关键作用。MEIS1 作为药理抑制背景下的一个有希望的靶点，我们鉴定了一种有效的髓系亲嗜性病毒整合位点 (MEIS) 抑制剂 MEISi-1，可在体外和体内诱导小鼠和人类 HSC 扩增。在这项工作中，我们通过合成 45 种新型类似物对 MEISi-1 进行了先导优化。构效关系研究揭示了环A上的对甲氧基和环B间位的疏水部分的重要性. 获得的生物学数据得到了抑制剂对接和分子动力学模拟研究的支持。11 种化合物被描述为强效抑制剂，证明对 MEIS1 和靶基因Meis1、Hif-1 α 和p21具有更好的抑制作用。其中，4h、4f和4b是最有效的抑制剂。预测的药代动力学特性满足药物相似性标准。此外，化合物对人皮肤成纤维细胞既没有细胞毒性，也没有致突变性。
• Discovery of certain benzyl/phenethyl thiazolidinone-indole hybrids as potential anti-proliferative agents: Synthesis, molecular modeling and tubulin polymerization inhibition study
  作者：Dilep Kumar Sigalapalli、Venkatesh Pooladanda、Priti Singh、Manasa Kadagathur、Sravanthi Devi Guggilapu、Jaya Lakshmi Uppu、Neelima D. Tangellamudi、Pavan Kumar Gangireddy、Chandraiah Godugu、Nagendra Babu Bathini

  DOI：10.1016/j.bioorg.2019.103188

  日期：2019.11

  A series of certain benzyl/phenethyl thiazolidinone-indole hybrids were synthesized for the study of anti-proliferative activity against A549, NCI-H460 (lung cancer), MDA-MB-231 (breast cancer), HCT-29 and HCT-15 (colon cancer) cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). We found that compound G37 displayed highest cytotoxicity with IC50 value of 0.92 +/- 0.12 mu M towards HCT-15 cancer cell line among all the synthesized compounds. Moreover, compound G37 was also tested on normal human lung epithelial cells (L132) and was found to be safe in contrast to HCT-15 cells. The lead compound G37 showed significant G2/M phase arrest in HCT-15 cells. Additionally, compound G37 significantly inhibited tubulin polymerization with IC50, value of 2.92 +/- 0.23 mu M. Mechanistic studies such as acridine orange/ethidium bromide (AO/EB) dual staining, DAPI nuclear staining, annexinV/propidium iodide dual staining, donogenic growth inhibition assays inferred that compound G37 induced apoptotic cell death in HCT-15 cells. Moreover, loss of mitochondrial membrane potential with elevated intracellular ROS levels was observed by compound G37. These compounds bind at the active pocket of the alpha/beta-tubulin with higher number of stable hydrogen bonds, hydrophobic and arene-cation interactions confirmed by molecular modeling studies.