2-氧代-2-(1H-吡咯-3-基)乙酸乙酯 | 87630-41-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-氧代-2-(1H-吡咯-3-基)乙酸乙酯
• 英文名称: ethyl pyrrole-3-glyoxalate
• 英文别名: ethyl 2-oxo-2-(1H-pyrrol-3-yl)acetate
• CAS: 87630-41-9
• 化学式: C₈H₉NO₃
• 分子量: 167.164
• InChiKey: BKXSEADUPAQLGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氧代-2-(1H-吡咯-3-基)乙酸乙酯 在 potassium phosphate 、 copper(l) iodide 、 sodium hypophosphite 、 palladium on carbon 、 (1S,2S)-(+)-1,2-环己二胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 48.0h， 生成 ethyl 2-[1-(6-indol-1-ylpyrazin-2-yl)pyrrol-3-yl]acetate
  参考文献：
  名称：

  Discovery and structure–activity relationship of 2,6-disubstituted pyrazines, potent and selective inhibitors of protein kinase CK2

  摘要：

  We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained potency. Then, introducing an aminoalkyl group at the 6-position of the indazole ring resulted in improved efficacy in both enzymatic and cell-based CK2 inhibition assays. Moreover, compound 13 showed selectivity against other kinases and in vivo efficacy in a rat nephritis model. These results show that 2,6-disubstituted pyrazines have potential as therapeutic agents for nephritis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.006
• 作为产物：
  描述：

  ethyl 1-(triisopropylsilyl)-3-pyrrolylglyoxalate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 生成 2-氧代-2-(1H-吡咯-3-基)乙酸乙酯
  参考文献：
  名称：

  β-取代的吡咯通过正三异丙基甲硅烷基吡咯的亲电取代。

  摘要：

  N-三异丙基甲硅烷基吡咯在C-3处经受主要或排他的动力学亲电取代，并且由此获得的化合物在与四丁基氟化铵进行甲硅烷基化后，以良好的总收率得到3-取代的吡咯。

  DOI：

  10.1016/s0040-4039(00)86011-6

文献信息

• Design, Synthesis, and Biological Evaluation of 3,4-Diarylmaleimides as Angiogenesis Inhibitors
  作者：Christian Peifer、Thomas Stoiber、Eberhard Unger、Frank Totzke、Christoph Schächtele、Dieter Marmé、Ruth Brenk、Gerhard Klebe、Dieter Schollmeyer、Gerd Dannhardt

  DOI：10.1021/jm0580297

  日期：2006.2.1

  The new analogue 2 of combretastatin A-4 was discovered to be an inhibitor of tubulin polymerization with an IC50 of 7.6 microM and reduced angiogenesis in the in vivo chick embryo model. Interestingly, in a series of 2,3-diarylmaleimides closely related to this lead, no other compound was found to be active in the tubulin polymerization assay. However, by screening in the in vivo chick embryo assay

  发现康美他汀A-4的新类似物2是微管蛋白聚合的抑制剂，在体内鸡胚模型中的IC50为7.6 microM，并减少了血管生成。有趣的是，在一系列与该铅紧密相关的2，3-二芳基马来酰亚胺中，在微管蛋白聚合测定中未发现其他化合物具有活性。然而，通过在体内进行筛选，将雏鸡胚胎测定法10鉴定为有效的血管生成抑制剂，表明了另一种靶标。确实，分子建模研究表明在模型激酶CDK2的ATP结合位点有一个合理的10结合模式。根据这些结果，在10种类似的12种蛋白激酶中筛选了10种类似物的抑制活性，发现10种对VEGF-R2的高亲和力表明IC50为2.5 nM。
• Design, Synthesis, and Evaluation of 3-Aryl-4-pyrrolyl-maleimides as Glycogen Synthase Kinase-3β Inhibitors
  作者：Qing Ye、Meng Li、Yu-Bo Zhou、Jia-Yu Cao、Lei Xu、Yu-Jin Li、Liang Han、Jian-Rong Gao、Yong-Zhou Hu、Jia Li

  DOI：10.1002/ardp.201300008

  日期：2013.5

  A series of 3‐aryl‐4‐pyrrolyl‐maleimides were designed, synthesized, and evaluated for their glycogen synthase kinase‐3β (GSK‐3β) inhibitory activity. Most compounds exhibited potent activity against GSK‐3β. Among them, compounds 11a, 11c, 11h, 11i, and 11j significantly reduced Aβ‐induced Tau hyperphosphorylation, showing the inhibition of GSK‐3β at the cellular level. Structure–activity relationships

  设计、合成了一系列 3-芳基-4-吡咯基-马来酰亚胺，并评估了它们的糖原合酶激酶-3β（GSK-3β）抑制活性。大多数化合物对 GSK-3β 表现出有效的活性。其中，化合物 11a、11c、11h、11i 和 11j 显着降低了 Aβ 诱导的 Tau 过度磷酸化，表明在细胞水平上抑制了 GSK-3β。基于获得的实验数据讨论了构效关系。
• β-substituted pyrroles via electrophilic substitution of n-triisopropylsilylpyrrole.
  作者：Joseph M Muchowski、Dennis R Solas

  DOI：10.1016/s0040-4039(00)86011-6

  日期：1983.1

  N-Triisopropylsilylpyrrole undergoes predominant or exclusive kinetic electrophilic substiution at C-3, and the compounds obtained thereby, upon desilylation with tetra--butylammonium fluoride, give 3-substituted pyrroles in good overall yields.

  N-三异丙基甲硅烷基吡咯在C-3处经受主要或排他的动力学亲电取代，并且由此获得的化合物在与四丁基氟化铵进行甲硅烷基化后，以良好的总收率得到3-取代的吡咯。
• Synthesis of Novel Furo-, Thieno-, and Pyrroloazepines
  作者：Roberto Martínez、Carlos Villarreal

  DOI：10.1055/s-0030-1257910

  日期：2010.10

  The synthesis of novel furo-, thieno-, and pyrroloazepine compounds, using the oxidative radical alkylation of three five-membered heterocyclic 3-acetic acid derivatives, is described. The bicyclic systems were obtained, via a small number of steps, directly from commercially available materials. oxidative radicals - carboxylic acid homologation - ­furan - thiophene - pyrrole - azepinones

  描述了使用三种五元杂环3-乙酸衍生物的氧化自由基烷基化反应合成新的呋喃，噻吩并吡咯并oa庚因化合物。双环体系是通过少量步骤直接从市售材料中获得的。 氧化自由基-羧酸同系物-呋喃-噻吩-吡咯-ze庚酮
• NITROGENOUS MACROCYCLIC COMPOUND, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION AND APPLICATION THEREOF
  申请人：Luoxin Pharmaceutical (Shanghai) Co., Ltd.

  公开号：EP3539960A1

  公开（公告）日：2019-09-18

  Disclosed in the present invention are a nitrogenous macrocyclic compound, a preparation method therefor, a pharmaceutical composition and an application thereof. The present invention provides a nitrogenous macrocyclic compound represented by formula III-0, a tautomer thereof, an optical isomer thereof, a hydrate thereof, a solvate thereof, a pharmacologically acceptable salt thereof, or a prodrug thereof. The compound can be effectively bond with bromodomains of a BET family: BRD4, BRD3, BRD2, and BRDT, so as to adjust transcription of a downstream gene c-myc and a related target gene thereof, and futher to adjust a downstream signal path and play a particular role, comprising treating diseases such as inflammatory diseases, cancers, and AIDS.

  本发明公开了一种含氮大环化合物、其制备方法、药物组合物及其应用。本发明提供了一种由式 III-0 表示的含氮大环化合物、其同分异构体、其光学异构体、其水合物、其溶液、其药理学上可接受的盐或其原药。该化合物可与 BET 家族的溴结构域有效结合：BRD4、BRD3、BRD2 和 BRDT，从而调节下游基因 c-myc 及其相关靶基因的转录，进而调节下游信号通路，发挥特殊作用，包括治疗炎症性疾病、癌症和艾滋病等疾病。