2-(5-fluoro-1H-indol-3-yl)-2-oxoacetyl chloride | 3828-09-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-(5-fluoro-1H-indol-3-yl)-2-oxoacetyl chloride
• CAS: 3828-09-9
• 化学式: C₁₀H₅ClFNO₂
• 分子量: 225.607
• InChiKey: OTOJFEFGCPXZGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.9
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2918300090

反应信息

• 作为反应物：
  描述：

  2-(5-fluoro-1H-indol-3-yl)-2-oxoacetyl chloride 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 生成 3-(benzofuran-3-yl)-4-(5-fluoro-1H-indol-3-yl)pyrrole-2,5-dione
  参考文献：
  名称：

  Structure-Based Design Leads to the Identification of Lithium Mimetics That Block Mania-like Effects in Rodents. Possible New GSK-3β Therapies for Bipolar Disorders

  摘要：

  More than two million American adults, or approximately one percent of the population 18 years or older, suffer from bipolar disorder. Current treatments include the so-called "mood stabilizers," lithium and valproic acid. Both are relatively dated drugs that are only partially effective and produce various undesirable side effects including weight gain. Based upon continued efforts to understand the molecular target for lithium, it now appears that specific inhibitors of the enzyme glycogen synthase kinase-3 beta (GSK-3 beta) may mimic the therapeutic action of mood stabilizers and might therefore allow for the design of improved drugs for treating patients with bipolar disorder as well as certain neurodegenerative disorders. Furthermore, the pro-apoptotic properties of the GSK-3 enzyme suggest the possible use of such inhibitors as neuroprotective agents. In fact, neuroprotection may contribute to the treatment of mood disorders. The present chemistry, modeling, and biology efforts have identified 3-benzofuranyl-4-indolylmaleimides as potent and relatively selective GSK-3 beta inhibitors. The best ligand in this series (having a K-i value of 4.6 nM against GSK-3 beta) was studied in a novel mouse model of mania that has recently been validated with several clinically effective mood stabilizers. This study presents the first demonstration of the efficacy of a GSK-3 beta inhibitor in this mouse model of mania. Selective brain penetrable GSK-3 ligands like those described herein become valuable research tools in better defining the role of this multifaceted kinase in both physiological and pathophysiological events.

  DOI：

  10.1021/ja068969w
• 作为产物：
  描述：

  5-氟吲哚 、 草酰氯 以 乙醚 为溶剂， 反应 0.5h， 生成 2-(5-fluoro-1H-indol-3-yl)-2-oxoacetyl chloride
  参考文献：
  名称：

  用于正电子发射断层显像的基于[18F]马来酰亚胺的糖原合酶激酶3β配体的开发。

  摘要：

  糖原合酶激酶3β（GSK-3β）的失调与神经退行性和精神病性疾病的发病机制有关。因此，开发用于正电子发射断层摄影（PET）成像的GSK-3β放射性示踪剂至关重要，因为这种无创成像技术可以更好地了解GSK-3β活性与活生物体中枢神经系统疾病之间的联系，从而可以及早发现该酶的异常活性。在此，我们报告了一系列高亲和力GSK-3β抑制剂氟取代的马来酰亚胺衍生物的合成和生物学评估。实现了潜在的GSK-3β示踪剂[18F] 10a的放射性合成。在啮齿动物中进行的体内PET初步成像研究显示，大脑摄取中等，尽管在大脑中未观察到饱和结合。有必要进一步完善铅支架，以开发用于中枢神经系统PET成像的[18F]标记的GSK-3放射性示踪剂。

  DOI：

  10.1021/acsmedchemlett.6b00405

文献信息

• Sequential one-pot synthesis of bis(indolyl)glyoxylamides: Evaluation of antibacterial and anticancer activities
  作者：Mukund P. Tantak、Vishakha Gupta、Kumar Nikhil、V. Arun、Rajnish Prakash Singh、Prabhat Nath Jha、Kavita Shah、Dalip Kumar

  DOI：10.1016/j.bmcl.2016.04.080

  日期：2016.7

  bis(indolyl)glyoxylamides were well characterized and tested for their antibacterial activity against Gram-positive and Gram-negative bacterial strains. Compounds 10d, 10g and 10i were found to display potent antibacterial activity against Gram-negative strain. Further, the cytotoxicity of bis(indolyl)glyoxylamides 10a-n were evaluated against a panel of human cancer cell lines. Of the screened analogues

  已经设计并合成了一系列的双（吲哚基）乙氧基叠氮化物10a-n。将来自易于获得的吲哚9与草酰氯的反应的原位生成的吲哚-3-乙二酰氯氯化物用色胺处理，以82-93％的产率生产双（吲哚基）乙二酰氧基叠氮化物10a-n。所有合成的双（吲哚基）乙醛酰乙酰胺均得到了很好的表征，并测试了它们对革兰氏阳性和革兰氏阴性细菌菌株的抗菌活性。发现化合物10d，10g和10i显示出对革兰氏阴性菌株的有效抗菌活性。此外，针对一组人类癌细胞系评估了双（吲哚基）乙氧基乙酰胺10a-n的细胞毒性。在筛选的类似物中，化合物10f（IC 50 ＝22.34μM； HeLa，24.05μM； PC-3，21.13μM； MDA-MB-231和29.94μM； MS-3，21.13μM； MDA-MB-231和29.94μM。BxPC-3）被确定为该系列中最有效的类似物。PC-3细胞暴露于10a或10f会导致裂解的PARP1水平
• 3-(7-Azaindolyl)-4-indolylmaleimides as a novel class of mutant isocitrate dehydrogenase-1 inhibitors: Design, synthesis, and biological evaluation
  作者：Yuanyuan Hu、Anhui Gao、Honghui Liao、Mengmeng Zhang、Gaoya Xu、Lixin Gao、Lei Xu、Yubo Zhou、Jianrong Gao、Qing Ye、Jia Li

  DOI：10.1002/ardp.201800039

  日期：2018.10

  A series of 3‐(7‐azainodyl)‐4‐indolylmaleimides was designed, synthesized, and evaluated for their isocitrate dehydrogenase 1 (IDH1)/R132H inhibitory activities. Many compounds such as 11a, 11c, 11e, 11g, and 11s exhibited favorable inhibitory effects on IDH1/R132H and were highly selective against the wild‐type IDH1. Evaluation of the biological activities at the cellular level showed that compounds

  设计、合成了一系列 3-(7-azainodyl)-4-indolylmaleimides，并评估了它们的异柠檬酸脱氢酶 1 (IDH1)/R132H 抑制活性。许多化合物如 11a、11c、11e、11g 和 11s 对 IDH1/R132H 表现出良好的抑制作用，并且对野生型 IDH1 具有高度选择性。在细胞水平上对生物活性的评估表明，化合物 11a、11c、11e、11g 和 11s 可以有效抑制表达 IDH1/R132H 的 U87MG 细胞中 2-羟基戊二酸的产生。基于获得的实验数据讨论了初步构效关系 (SAR) 和分子建模研究。这些发现可能为开发新型 IDH1/R132H 抑制剂提供新的见解。
• Novel, potent and selective cyclin D1/CDK4 inhibitors: indolo[6,7-a]pyrrolo[3,4-c]carbazoles
  作者：Thomas A. Engler、Kelly Furness、Sushant Malhotra、Concha Sanchez-Martinez、Chuan Shih、Walter Xie、Guoxin Zhu、Xun Zhou、Scott Conner、Margaret M. Faul、Kevin A. Sullivan、Stanley P. Kolis、Harold B. Brooks、Bharvin Patel、Richard M. Schultz、Tammy B. DeHahn、Kashif Kirmani、Charles D. Spencer、Scott A. Watkins、Eileen L. Considine、Jack A. Dempsey、Catherine A. Ogg、Nancy B. Stamm、Bryan D. Anderson、Robert M. Campbell、Vasu Vasudevan、Michelle L. Lytle

  DOI：10.1016/s0960-894x(03)00461-x

  日期：2003.7

  The synthesis and CDK inhibitory properties of a series of indolo[6,7-a]pyrrolo[3,4-c]carbazoles is reported. In addition to their potent CDK activity, the compounds display antiproliferative activity against two human cancer cell lines. These inhibitors also effect strong G1 arrest in these cell lines and inhibit Rb phosphorylation at Ser780 consistent with inhibition of cyclin D1/CDK4.

  报道了一系列吲哚[6，7-a]吡咯并[3，4-c]咔唑的合成和CDK抑制性能。这些化合物除了具有强大的CDK活性外，还具有针对两种人类癌细胞系的抗增殖活性。这些抑制剂还影响这些细胞系中的强G1阻滞，并抑制Ser780处的Rb磷酸化，这与抑制细胞周期蛋白D1 / CDK4一致。
• Structural Simplification of Marine Natural Products: Discovery of Hamacanthin Derivatives Containing Indole and Piperazinone as Novel Antiviral and Anti-phytopathogenic-fungus Agents
  作者：Tienan Wang、Lin Li、Yanan Zhou、Aidang Lu、Hongyan Li、Jianxin Chen、Zhongyu Duan、Qingmin Wang

  DOI：10.1021/acs.jafc.1c04098

  日期：2021.9.8

  designed, synthesized, and studied on the antiviral and antifungal activities. Most of these compounds displayed higher antiviral activities than ribavirin. The antiviral activities of compounds 1a and 13e–13h are similar to or higher than that of ningnanmycin (perhaps the most efficient anti-plant-virus agent). Compound 13h was selected for further antiviral mechanism research via transmission electron

  随着植物病害的日益严重和病原体抗性的出现，迫切需要开发新型高效、环保的农药。海洋天然产物（MNP）资源丰富多样。基于 MNP 的结构简化是寻找新型农药候选物的重要策略。在这项工作中，海洋天然产物 6"-debromohamacanthin A ( 1a ) 被有效地制备并选择为母体结构。设计、合成了一系列金黄素衍生物，并研究了其抗病毒和抗真菌活性。大多数这些化合物显示出比利巴韦林更高的抗病毒活性。化合物1a和13e – 13h的抗病毒活性与宁南霉素（可能是最有效的抗植物病毒剂）相似或更高。通过透射电子显微镜、分子对接和荧光滴定，选择化合物13h进行进一步的抗病毒机制研究。结果表明，化合物13h可与TMV CP结合，干扰TMV CP与RNA的组装过程。此外，这些金黄素衍生物还对八种常见的农业病原体表现出广谱抑制作用。化合物1a、12b和12f具有优异的杀菌活性，可作为新的杀菌候选物进行进一步
• ARYL HYDROCARBON RECEPTOR MODULATOR
  申请人：Ariagen, Inc.

  公开号：US20190307731A1

  公开（公告）日：2019-10-10

  Disclosed is an aryl hydrocarbon receptor modulator of formula (I), and a pharmaceutically acceptable salt thereof, wherein R′ is H, CN, CH 2 (OH)R 0 , C m H 2m+1 , C n H 2n-1 , C n H 2n-3 , two R a are independently H or two R a together form ═O or ═N—W 3 —R 1 ; A is a C 6 to C 10 aromatic ring unsubstituted or substituted with 1 to 3 R, or a C 2 -C 10 heteroaromatic ring interrupted by 1 to 5 heteroatoms selected from N, O, and S or a 4 to 7 membered nonaromatic heterocyclic ring containing C═N and interrupted by 1 to 3 heteroatoms selected from N, O, and S, with either one unsubstituted or substituted with 1 to 3 R; Q is R, or is a C 6 to C 10 aromatic ring or a C 2 to C 10 heteroaromatic ring unsubstituted or substituted with 1 to 3 R and interrupted by 1 to 5 heteroatoms selected from N, O, and S; and R is R c which is C-attached or R N which is N-attached. The compounds of formula (I) of the present invention can regulate AhR activity, and can be used to inhibit the growth of cancer cells and inhibit the metastasis and invasion of tumor cells.

  本发明揭示了一种化学式（I）的芳香烃受体调节剂及其药用可接受盐，其中R′为H、CN、CH2（OH）R0、CmH2m+1、CnH2n-1、CnH2n-3，两个Ra独立地为H或两个Ra共同形成═O或═N—W3—R1；A为未取代或取代1至3个R的C6至C10芳香环，或由N、O和S中选择的1至5个杂原子中断的C2-C10杂芳环，或含有C═N并由N、O和S中选择的1至3个杂原子中断的4至7个成员的非芳杂环，其中一个未取代或取代1至3个R；Q为R，或者是未取代或取代1至3个R并由N、O和S中断的C6至C10芳香环或C2至C10杂芳环；R为C-连接的Rc或N-连接的RN。本发明的化合物可以调节AhR活性，可用于抑制癌细胞的生长，以及抑制肿瘤细胞的转移和侵袭。