3-chloro-4-fluorophenyl 2-bromoacetamide | 349121-13-7

• 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: 3-chloro-4-fluorophenyl 2-bromoacetamide
• 英文别名: 2-bromo-N-(3-chloro-4-fluorophenyl)acetamide
• CAS: 349121-13-7
• 化学式: C₈H₆BrClFNO
• mdl: MFCD02676799
• 分子量: 266.497
• InChiKey: KYGXRNBDSUCFNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-chloro-4-fluorophenyl 2-bromoacetamide 在 copper(l) iodide 、 sodium azide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (Z)-N-(3-chloro-4-fluorophenyl)-2-[4-({3-(furan-2-ylmethyl)-4-(trifluoromethyl)-2-[4-(trifluoromethyl)phenylimino]thiazolidin-4-yloxy}methyl)-1H-1,2,3-triazol-1-yl]acetamide
  参考文献：
  名称：

  Appalanaidu, K.; Dadmal, Tulshiram L.; Kumbhare, Ravindra M., Indian Journal of Heterocyclic Chemistry, 2021, vol. 31, # 1, p. 81 - 89

  摘要：

  DOI：
• 作为产物：
  描述：

  3-氯-4-氟苯胺 、 溴乙酰溴 在 碳酸氢钠 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 1.0h， 生成 3-chloro-4-fluorophenyl 2-bromoacetamide
  参考文献：
  名称：

  新型吡唑并嘧啶基衍生物的设计和合成作为可逆的 BTK 抑制剂，在套细胞淋巴瘤中具有有效的抗增殖活性

  摘要：

  布鲁顿酪氨酸激酶（BTK）抑制剂的开发在B细胞恶性肿瘤和自身免疫性疾病的治疗中具有重要的价值和意义。在此，设计了一类新型的基于吡唑并嘧啶的 BTK 抑制剂，并在套细胞淋巴瘤 (MCL) 细胞系中进行了评估。我们证明，与先导化合物相比，目标化合物在提高抗增殖活性方面取得了很大进展。化合物13c、13g、13h、13l、13n和13o在 MCL 细胞系中表现出有效的抗增殖活性，具有个位数微摩尔效力。此外，化合物13l在 Z138 细胞中以剂量依赖性方式特别扰乱线粒体膜电位并增加活性氧水平。13l通过半胱天冬酶 3 介导的 Z138 细胞凋亡途径诱导细胞凋亡。总体而言，这项研究为开发抗肿瘤药物提供了有价值的先导化合物。

  DOI：

  10.1007/s00044-022-02861-7

文献信息

• Synthesis of novel fluoro 1,2,3-triazole tagged amino bis(benzothiazole) derivatives, their antimicrobial and anticancer activity
  作者：Ravindra M. Kumbhare、Tulshiram L. Dadmal、R. Pamanji、Umesh B. Kosurkar、L. R. Velatooru、K. Appalanaidu、Y. Khageswara Rao、J. Venkateswara Rao

  DOI：10.1007/s00044-014-1006-0

  日期：2014.10

  A new series of fluoro 1,2,3-triazole tagged amino bis (benzothiazole) derivatives 8, 9 were prepared starting from 2-amino benzothiazole in four steps via amination, cyclization, alkylation followed by reaction with various azides under sharpless conditions through click chemistry approach. All newly synthesized compounds were screened for their antimicrobial and cytotoxic activity against four human cancer cell lines (U937, THP-1, Colo205, and A549), and promising compounds have been identified.
• Design and synthesis of novel 1-substituted 3-(6-phenoxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine analogs as selective BTK inhibitors for the treatment of mantle cell lymphoma
  作者：Fansheng Ran、Yang Liu、Shengping Yu、Kaiwen Guo、Wendi Tang、Xin Chen、Guisen Zhao

  DOI：10.1016/j.bioorg.2019.103367

  日期：2020.1

  Ibrutinib (IBN), a first-in-class BTK-inhibitor, was approved by the FDA for the treatment of mantle cell lymphoma (MCL). Although IBN shows excellent performance as an anti-lymphoma agent, it has some undesirable side effects due to its off-target activities. Our studies yielded a novel series of 3-(6-phenoxypyridin-3-yl)-4-amine-1H-pyrazolo [3,4-d]pyrimidine derivatives capable of potent inhibition of Bruton's tyrosine kinase (BTK). Notably, compound 13e explained potent BTK inhibitory activity and could completely inhibit the phosphorylation of BTK and PLC gamma 2 in Z138 cells at low micromolar concentration. Compared with IBN, compound 13e improved anti-proliferative activities 3-40 folds in MCL cell lines with IC50 values lower than 1 mu M. Low micromolar doses of 13e could induce strong cell apoptosis in Jeko-1 and Z138 cells. In addition, compound 13e showed greater BTK selectivity and higher stability in human liver microsomes than IBN and potential safety improvement for the treatment of MCL.
• Synthesis and structure–activity relationships of piperidine-based melanin-concentrating hormone receptor 1 antagonists
  作者：Wen-Lian Wu、Duane A. Burnett、Richard Spring、Li Qiang、Thavalakulamgara K. Sasikumar、Martin S. Domalski、William J. Greenlee、Kim O’Neill、Brian E. Hawes

  DOI：10.1016/j.bmcl.2006.04.061

  日期：2006.7

  Isosteric replacement of the urea group of lead compound 1 led to novel substituted piperidine phenylamide analogues. SAR on the electron-induced effects of various linkers as well as substituents on the phenyl rings and the piperidine nitrogen has been investigated. Many single-digit nanomolar MCH R1 antagonists have been identified from this series. (c) 2006 Elsevier Ltd. All rights reserved.
• Appalanaidu, K.; Dadmal, Tulshiram L.; Kumbhare, Ravindra M., Indian Journal of Heterocyclic Chemistry, 2021, vol. 31, # 1, p. 81 - 89
  作者：Appalanaidu, K.、Dadmal, Tulshiram L.、Kumbhare, Ravindra M.、Pamanji, R.、Rao, J. Venkateswara、Reddy, Prathyusha J.、Velatooru, L. R.

  DOI：——

  日期：——
• Design and synthesis of novel pyrazolopyrimidine-based derivatives as reversible BTK inhibitors with potent antiproliferative activity in mantle cell lymphoma
  作者：Fansheng Ran、Yang Liu、Guisen Zhao

  DOI：10.1007/s00044-022-02861-7

  日期：2022.4

  evaluated in mantle cell lymphoma (MCL) cell lines. We demonstrated that target compounds had made great progress in improvement of antiproliferative activity compared to lead compound. Compounds 13c, 13g, 13h, 13l, 13n and 13o demonstrated effectively antiproliferative activity in MCL cells lines with single-digit micromolar potency. Furthermore, compound 13l specifically disturbed mitochondrial membrane

  布鲁顿酪氨酸激酶（BTK）抑制剂的开发在B细胞恶性肿瘤和自身免疫性疾病的治疗中具有重要的价值和意义。在此，设计了一类新型的基于吡唑并嘧啶的 BTK 抑制剂，并在套细胞淋巴瘤 (MCL) 细胞系中进行了评估。我们证明，与先导化合物相比，目标化合物在提高抗增殖活性方面取得了很大进展。化合物13c、13g、13h、13l、13n和13o在 MCL 细胞系中表现出有效的抗增殖活性，具有个位数微摩尔效力。此外，化合物13l在 Z138 细胞中以剂量依赖性方式特别扰乱线粒体膜电位并增加活性氧水平。13l通过半胱天冬酶 3 介导的 Z138 细胞凋亡途径诱导细胞凋亡。总体而言，这项研究为开发抗肿瘤药物提供了有价值的先导化合物。