(2E)-3-(2-萘基)-2-丁烯酰氯 | 321675-01-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 中文名称: (2E)-3-(2-萘基)-2-丁烯酰氯
• 英文名称: (E)-3-Naphthalen-2-yl-but-2-enoyl chloride
• 英文别名: 2-Butenoyl chloride,3-(2-naphthalenyl)-,(2E)-；(E)-3-naphthalen-2-ylbut-2-enoyl chloride
• CAS: 321675-01-8
• 化学式: C₁₄H₁₁ClO
• 分子量: 230.694
• InChiKey: DBZSKMGYRKKNEZ-CSKARUKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (2E)-3-(2-萘基)-2-丁烯酰氯 在 吡啶 、 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 12.0h， 生成 (E)-2-(3-(naphthalen-2-yl)but-2-enamido)-5-(trimethylstannyl)benzoic acid
  参考文献：
  名称：

  Targeting telomerase with radiolabeled inhibitors

  摘要：

  The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells, I-123-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An I-123-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC50 of 1.58 mu M (MST-312 IC50: 0.23 mu M). Clonogenic assays showed a dose dependant effect of I-123-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435. (C) 2016 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2016.09.028
• 作为产物：
  描述：

  (E)-3-(萘-2-基)丁-2-烯酸甲酯 在 lithium hydroxide 、 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 生成 (2E)-3-(2-萘基)-2-丁烯酰氯
  参考文献：
  名称：

  Inhibition of telomerase by BIBR 1532 and related analogues

  摘要：

  BIBR 1532 has been reported to be a potent, small molecule inhibitor of human telomerase, suggesting it as a lead for the development of anti-telomerase therapy. We confirm the ability of BIBR 1532 to inhibit telomerase and report the discovery of an equally potent analogue. Importantly, IC50 values in cell extract are considerably higher than those previously reported using assays for purified enzyme, indicating that substantial improvement may be necessary. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00101-x

文献信息

• Design, synthesis and SARs of novel telomerase inhibitors based on BIBR1532
  作者：Chao Liu、Hua Zhou、Xiao Bao Sheng、Xin Hua Liu、Fei Hu Chen

  DOI：10.1016/j.bioorg.2020.104077

  日期：2020.9

  their telomerase inhibitory activity were tested. Among them, eight compounds showed good activity against cancer cells, among them compounds 56, 57 and 59 also showed low toxicity. Some of them showed excellent telomerase inhibitory activity with IC50 values ranging from 0.62 μM to 8.87 μM. Based on above, in depth structure-activity relationships were summarized, the compounds by replacing methyl group

  端粒酶已成为开发抗肿瘤药物的新的流行靶标之一。根据已进入临床研究阶段的BIBR1532的结构特征，设计并合成了6个系列的64种具有不同结构特征的新化合物。测试了对SGC-7901，MGC-803，SMMC-7721，A375和GES细胞系的抑制活性及其端粒酶抑制活性。其中，8个化合物显示良好的活性针对癌细胞，其中化合物56，57和59还显示出低毒性。其中一些对IC 50表现出优异的端粒酶抑制活性值范围从0.62μM到8.87μM。据此，在深度构效关系上进行了总结，用氰化物取代甲基并保留酰胺部分的化合物具有良好的抗肿瘤活性，中等的细胞毒性和较好的端粒酶抑制活性。该结果应在基于BIBR1532的结构优化中用作进一步开发小分子端粒酶抑制剂的参考。
• [EN] TELOMERASE REVERSE TRANSCRIPTASE DEGRADERS AND METHODS OF USE THEREOF<br/>[FR] AGENTS DE DÉGRADATION DE LA TRANSCRIPTASE INVERSE DE LA TÉLOMÉRASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：WISTAR INST

  公开号：WO2020252195A1

  公开（公告）日：2020-12-17

  The present disclosure provides TERT inhibitor compounds, a TERT inhibitor linked to a ubiquitin ligase ligand, as well as pharmaceutical compositions thereof. The present disclosure also provides methods of inhibiting telomerase reverse transcriptase (TERT) and methods of treating or preventing a disease or disorder using said compounds and/or compositions.

  本公开提供了TERT抑制剂化合物，一个与泛素连接酶配体相关的TERT抑制剂，以及其药物组成物。本公开还提供了通过使用上述化合物和/或组成物来抑制端粒酶逆转录酶（TERT）的方法，以及治疗或预防疾病或紊乱的方法。
• Targeting telomerase with radiolabeled inhibitors
  作者：Philip A. Waghorn、Mark R. Jackson、Veronique Gouverneur、Katherine A. Vallis

  DOI：10.1016/j.ejmech.2016.09.028

  日期：2017.1

  The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells, I-123-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An I-123-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC50 of 1.58 mu M (MST-312 IC50: 0.23 mu M). Clonogenic assays showed a dose dependant effect of I-123-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435. (C) 2016 The Authors. Published by Elsevier Masson SAS.
• Inhibition of telomerase by BIBR 1532 and related analogues
  作者：D.K Barma、Anissa Elayadi、J.R Falck、David R Corey

  DOI：10.1016/s0960-894x(03)00101-x

  日期：2003.4

  BIBR 1532 has been reported to be a potent, small molecule inhibitor of human telomerase, suggesting it as a lead for the development of anti-telomerase therapy. We confirm the ability of BIBR 1532 to inhibit telomerase and report the discovery of an equally potent analogue. Importantly, IC50 values in cell extract are considerably higher than those previously reported using assays for purified enzyme, indicating that substantial improvement may be necessary. (C) 2003 Elsevier Science Ltd. All rights reserved.