3-fluorophenyl chloroformate | 68622-07-1

• 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: 3-fluorophenyl chloroformate
• 英文别名: (3-fluorophenyl) carbonochloridate
• CAS: 68622-07-1
• 化学式: C₇H₄ClFO₂
• 分子量: 174.559
• InChiKey: UIEYPDNYJMIKMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-fluorophenyl chloroformate 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 C₁₁H₁₃FN₂O₂
  参考文献：
  名称：

  Novel artemisinin derivatives with potent anticancer activities and the anti-colorectal cancer effect by the mitochondria-mediated pathway

  摘要：

  Many artemisinin derivatives have good inhibitory effects on malignant tumors. In this work, a novel series of artemisinin derivatives containing piperazine and fluorine groups were designed and synthesized and their structures were confirmed by ¹H NMR, ¹³C NMR and HRMS technologies. The in vitro cytotoxicity against various cancer cell lines was evaluated. Among the derivatives, compound 12h was found to exhibit not only the best activity against HCT-116 cells (IC₅₀ = 0.12 ± 0.05 μM), but also low toxicity against normal cell line L02 (IC₅₀ = 12.46 ± 0.10 μM). The mechanisms study revealed that compound 12h caused the cell cycle arrest in G1 phase, induced apoptosis in a concentration-dependent manner, significantly reduced mitochondrial membrane potential, increased intracellular ROS and Ca²⁺ levels, up-regulated the expression of Bax, cleaved caspase-9, cleaved caspase-3, and down-regulated the expression of Bcl-2 protein. A series of analyses confirmed that 12h can inhibit HCT-116 cells migration and induce apoptosis by a mechanism of the mitochondria-mediated pathway in the HCT-116 cell line. The present work indicates that compound 12h may merit further investigation as a potential therapeutic agent for colorectal cancer.

  DOI：

  10.1016/j.bioorg.2020.104496
• 作为产物：
  描述：

  三光气 、 3-氟苯酚 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 3-fluorophenyl chloroformate
  参考文献：
  名称：

  Novel artemisinin derivatives with potent anticancer activities and the anti-colorectal cancer effect by the mitochondria-mediated pathway

  摘要：

  Many artemisinin derivatives have good inhibitory effects on malignant tumors. In this work, a novel series of artemisinin derivatives containing piperazine and fluorine groups were designed and synthesized and their structures were confirmed by ¹H NMR, ¹³C NMR and HRMS technologies. The in vitro cytotoxicity against various cancer cell lines was evaluated. Among the derivatives, compound 12h was found to exhibit not only the best activity against HCT-116 cells (IC₅₀ = 0.12 ± 0.05 μM), but also low toxicity against normal cell line L02 (IC₅₀ = 12.46 ± 0.10 μM). The mechanisms study revealed that compound 12h caused the cell cycle arrest in G1 phase, induced apoptosis in a concentration-dependent manner, significantly reduced mitochondrial membrane potential, increased intracellular ROS and Ca²⁺ levels, up-regulated the expression of Bax, cleaved caspase-9, cleaved caspase-3, and down-regulated the expression of Bcl-2 protein. A series of analyses confirmed that 12h can inhibit HCT-116 cells migration and induce apoptosis by a mechanism of the mitochondria-mediated pathway in the HCT-116 cell line. The present work indicates that compound 12h may merit further investigation as a potential therapeutic agent for colorectal cancer.

  DOI：

  10.1016/j.bioorg.2020.104496

文献信息

• Structure–activity relationship studies on 1-(5-carboxyindol-1-yl)-propan-2-one inhibitors of human cytosolic phospholipase A2α: Variation of the activated ketone moiety
  作者：Martina Kaptur、Alwine Schulze Elfringhoff、Matthias Lehr

  DOI：10.1016/j.bmcl.2011.01.085

  日期：2011.3

  relationship studies, we investigated the effect of the substitution of the electrophilic ketone group in the middle part of the molecule by other polar residues, such as hydroxyimino, azido, acyloxy, acylamino, urea and carbamate, on enzyme inhibition. With an IC50 of 1.7 μM against cPLA2α from human platelets, the 4-fluorophenylcarbamate derivative 23f was the most active of the compounds tested.

  吲哚-5-羧酸与在位置1 3-芳氧基-2-氧代丙基残基已被发现是人类的有效抑制剂胞浆型磷脂酶甲2 α（与cPLA 2 α）。在结构-活性关系研究过程中，我们研究了分子中部的亲电子酮基团被其他极性残基（例如羟基亚氨基，叠氮基，酰氧基，酰氨基，尿素和氨基甲酸酯）取代对酶抑制的影响。与IC 50针对与cPLA 1.7μM 2从人血小板α，4-氟苯衍生物23F是最活跃的测试化合物。
• Enantioselective synthesis of 1-vinyltetrahydroisoquinolines via Pd-catalyzed intramolecular asymmetric allylic amination reactions
  作者：Chih-Wei Chien、Ce Shi、Chi-Feng Lin、Iwao Ojima

  DOI：10.1016/j.tet.2011.05.125

  日期：2011.9

  naturally occurring isoquinoline alkaloids. 1-Vinyl-6,8-dimethoxytetrahydroisoquinoline 4 and 1-vinyl-5,6,7-trimethoxytetrahydroisoquinoline 6 with >90% ee by means of Pd-catalyzed intramolecular asymmetric allylic amination reactions, using MPN and BOP ligands, developed in our laboratory. The fine-tuning capability of the MPN and BOP ligands has played a significant role in the optimization of enantioselectivity

  1-乙烯基四氢异喹啉用作合成多种天然存在的异喹啉生物碱的通用中间体。1-乙烯基-6,8-二甲氧基四氢异喹啉4和1-乙烯基-5,6,7-三甲氧基四氢异喹啉6使用MPN和BOP配体，通过我们实验室开发的Pd催化的分子内不对称烯丙基胺化反应，可以得到ee> 90％的有机物。MPN和BOP配体的微调功能在优化对映选择性方面发挥了重要作用。观察到有趣的取代基效应以及溶剂效应对产物的选择性和对映选择性。提出了可能的机制，其可以适应各种发现，包括通过其与路易斯酸性Pd 2+金属中心的配位来激活三氟酰胺部分的至关重要性。
• Synthesis and SAR studies of 1,4-diazabicyclo[3.2.2]nonane phenyl carbamates – subtype selective, high affinity α7 nicotinic acetylcholine receptor agonists
  作者：Christopher J. O’Donnell、Langu Peng、Brian T. O’Neill、Eric P. Arnold、Robert J. Mather、Steven B. Sands、Alka Shrikhande、Lorraine A. Lebel、Douglas K. Spracklin、Frank M. Nedza

  DOI：10.1016/j.bmcl.2009.06.059

  日期：2009.8

  4-diazabicyclo[3.2.2]nonane phenyl carbamate series of α7 nAChR agonists is described. The development of the medicinal chemistry strategy and SAR which led to the identification of 5 and 7aa as subtype selective, high affinity α7 agonists as excellent leads for further evaluation is discussed, along with key physicochemical and pharmacokinetic data highlighting their lead potential.

  描述了有关α7nAChR激动剂的1,4-二氮杂双环[3.2.2]壬烷苯基氨基甲酸酯系列的双环胺，氨基甲酸酯连接基和芳环的合成和SAR研究。讨论了药物化学策略和SAR的发展，从而将5和7aa鉴定为亚型选择性，高亲和力α7激动剂，作为进一步评估的极好线索，并讨论了突出其潜在潜力的重要理化和药代动力学数据。
• Adenosine receptor ligands
  申请人：——

  公开号：US20030134873A1

  公开（公告）日：2003-07-17

  The present application relates to compounds of the formula 1 wherein R 1 is hydrogen, halogen or lower alkoxy; R 2 is hydrogen or is —C(O)-lower alkyl or —C(O)-phenyl, wherein the phenyl ring is unsubstituted or substituted by one or two substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy and trifluoromethyl, or is —C(O)-furanyl or —C(O)-thiophenyl, wherein the rings are unsubstituted or substituted by halogen; or a pharmaceutically acceptable salt thereof. The compounds are useful in the treatment of diseases associated with the adenosine A 2 receptor.

  本申请涉及以下式1的化合物，其中R1为氢、卤素或较低的烷氧基；R2为氢，或者为—C(O)-较低烷基或—C(O)-苯基，其中苯环未取代或取代为来自卤素、较低烷基、较低烷氧基和三氟甲基的一种或两种取代基，或者为—C(O)-呋喃基或—C(O)-噻吩基，其中环未取代或取代为卤素；或其药学上可接受的盐。这些化合物在治疗与腺苷A2受体相关的疾病中有用。
• Design, Preparation and Studies Regarding Cytotoxic Properties of Glycyrrhetinic Acid Derivatives
  作者：Qing-Xuan Zheng、Rui Wang、Yan Xu、Chang-Xin He、Cai-Yun Zhao、Zhi-Fang Wang、Rui Zhang、Wim Dehaen、Hui-Jing Li、Qi-Yong Huai

  DOI：10.1248/bpb.b19-00615

  日期：2020.1.1

  Glycyrrhetinic acid (GA) is a natural product with certain antitumor activity. In order to enhance the cytotoxicity, a total of eighteen derivatives of GA were designed and synthesized. Their cytotoxicity against MDA-MB-231cells (human breast cancer cells) and HeLa cells (human cervical cancer cells), were evaluated by the MTT method (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide).

  甘草次酸（GA）是一种具有一定抗肿瘤活性的天然产物。为了增强细胞毒性，设计并合成了总共18种GA衍生物。通过MTT法（3-（4,5-二甲基噻唑-2-基）-2、5-二苯基四唑鎓）评价了它们对MDA-MB-231细胞（人乳腺癌细胞）和HeLa细胞（人宫颈癌细胞）的细胞毒性。溴化物）。结果表明，这些目标化合物具有较宽的摩尔活性范围，其中一些具有比商品药物吉非替尼和阿霉素更好的活性。化合物6g分别以5、10和20 µM诱导7、10和44％的MDA-MB-231细胞凋亡。