1-acetyl-3-formyl-7-azaindole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 1-acetyl-3-formyl-7-azaindole
• 英文别名: 1-acetyl-1H-7-aza-1H-indole-3-carbaldehyde；1-acetyl-7-azaindole-3-carboxaldehyde；1-acetyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde；1-acetylpyrrolo[2,3-b]pyridine-3-carbaldehyde
• 化学式: C₁₀H₈N₂O₂
• mdl: MFCD12027500
• 分子量: 188.186
• InChiKey: LWAZRVDLUPXTIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  52
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-acetyl-3-formyl-7-azaindole 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 以30%的产率得到1-乙酰基-1,2-二氢-3H-吡咯并[2,3-b]吡啶-3-酮
  参考文献：
  名称：

  1-取代-3 H-吡咯并[2,3 - b ]吡啶-3-酮的合成与反应性

  摘要：

  通过Baeyer-Villiger氧化获得了1-取代的吡咯并[2,3-b]吡啶-3-酮（7-氮杂吲哚酮）。7-氮杂吲哚满酮与芳族醛的反应产生2-取代的-7-氮杂吲哚满酮。已经描述了吡啶并[3'，2'：4,5]吡咯并[3,2-b]萘啶的合成。

  DOI：

  10.1016/s0040-4039(00)73031-0
• 作为产物：
  描述：

  7-氮杂吲哚 在 4-二甲氨基吡啶 、 乌洛托品 、 溶剂黄146 、 三乙胺 作用下， 反应 7.0h， 生成 1-acetyl-3-formyl-7-azaindole
  参考文献：
  名称：

  7,7′-Diazaindirubin—A small molecule inhibitor of casein kinase 2 in vitro and in cells

  摘要：

  Aza- and diaza-bisindoles were synthesized by coupling of 7-azaisatin, 7-azaoxindol, 7-azaindoxyl acetate, and their non-aza counterparts, respectively. Whereas 7,7'-diazaindigo (10) and 7,7'-diazaisoindigo (11) did not show antiproliferative activity in several human tumor cell lines up to 100 mu M, 7-azaindirubin (12) and 7'-azaindirubin (13) were more active than the parent molecule, indirubin, in LXFL529L cells (human large cell lung tumor xenograft), and 7,7'-diazaindirubin (14) was exhibiting substantially enhanced growth inhibitory activity in these cells. In the NCI 60 cell line panel, 14 displayed antiproliferative activity preferentially in certain melanoma and non-small cell lung cancer cells. In contrast to the potent serine/threonine/tyrosine kinase inhibition observed for indirubins, kinase inhibition profiling of 14 in 220 kinases revealed largely a loss of kinase inhibitory activity towards most kinases, with retained inhibitory activity for just a few kinases. At 1 mu M concentration, especially casein kinases CK1 gamma 3, CK2 alpha, CK2 alpha 2, and SIK were inhibited by more than 50%. In cell-based assays, 14 markedly affected CK2-mediated signaling in various human tumor cells. In MCF7 cells, 14 induced cell cycle arrest at G1 and G2/M and apoptosis, whereas CK2-deficient MCF7 cells were resistant. These findings reveal a novel key mechanism of action for 14, suggesting primarily CK2 inhibition to be causally related to growth inhibition of human tumor cells. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.031

文献信息

• Synthesis and antifungal activity of novel streptochlorin analogues
  作者：Ming-Zhi Zhang、Qiong Chen、Cai-Hong Xie、Nick Mulholland、Sarah Turner、Dianne Irwin、Yu-Cheng Gu、Guang-Fu Yang、John Clough

  DOI：10.1016/j.ejmech.2015.01.043

  日期：2015.3

  is an indole natural products with a variety of biological activities. Based on the methods developed for the synthesis of pimprinine in our laboratory, we have synthesized a series of indole-modified streptochlorin analogues and measured their activities against seven phytopathogenic fungi. Some of the analogues displayed good activity in the primary assays, and the seven compounds 10b, 10c, 11e

  链霉菌素是1988年从链霉菌属菌丝体的亲脂性提取物中首次分离出的新抗生素，是一种具有多种生物活性的吲哚天然产物。根据在我们实验室开发的合成嘧啶的方法，我们合成了一系列吲哚修饰的链霉素类似物，并测量了它们对七种植物病原真菌的活性。一些类似物在第一测定中显示良好的活性，和七个化合物10b的，10C，11E，13E，21，22C和22E（如图1所示）被确定为最有希望进行进一步研究的候选人。结构优化仍在进行中，目的是发现具有改进的抗真菌活性的合成类似物。
• 7-Azaindolequinuclidinones (7-AIQD): A novel class of cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor ligands
  作者：Narsimha Reddy Penthala、Amal Shoeib、Soma Shekar Dachavaram、Christian V. Cabanlong、Jingfang Yang、Chang-Guo Zhan、Paul L. Prather、Peter A. Crooks

  DOI：10.1016/j.bmcl.2020.127501

  日期：2020.11

  been synthesized and evaluated for affinity toward CB1 and CB2 cannabinoid receptors and identified as a novel class of cannabinoid receptor ligands. Structure–activity relationship (SAR) studies indicate that 7-AIQD analogs are dual CB1/CB2 receptor ligands exhibiting high potency with somewhat greater selectivity towards CB2 receptors compared to the previously reported indolequinuclidinone (IQD)

  已经合成了一系列N-苄基-7-氮杂吲哚喹啉酮 (7-AIQD) 类似物，并评估了对 CB1 和 CB2 大麻素受体的亲和力，并被确定为一类新型的大麻素受体配体。构效关系 (SAR) 研究表明，7-AIQD 类似物是双 CB1/CB2 受体配体，与之前报道的吲哚喹核酮 (IQD) 类似物相比，对 CB2 受体的选择性更高。初始结合测定表明，7-AIQD 类似物8b、8d、8f、8g和9b (1 μM) 使 CB1/CB2 非选择性激动剂 CP-55,940 (0.1 nM) 产生超过 50% 的置换。此外，基从完全竞争结合曲线确定的值表明，相对于 CB1 受体，类似物8a、8b和8g对 CB2 表现出高亲和力（分别为 110、115 和 23.7 nM）和中等选择性（分别为 26.3、6.1 和 9.2 倍）。检查 G 蛋白活性调节的功能研究表明，8a作为 CB1 和 CB2 受体的中性拮抗
• 7-azaindirubins, 7'-azaindirubins, 7-7'-diazaindirubin and the corresponding 3'-oxime ether derivates: production thereof, their production and use as a medicament
  申请人：Technische Universität Kaiserslautern

  公开号：EP2199292A1

  公开（公告）日：2010-06-23

  The present invention relates to 7-azaindirubins (1), 7'-azaindirubins (2), and 7,7'-diaza-indirubins (3), wherein E, R1 and R2 have the meanings detailed in the description, their production and use as a medicament for treating cancer, neurodegenerative diseases, bipolar disorders, inflammatory and infectious diseases, including viral diseases. Depending on structure, these indirubins act as inhibitors of various kinases involved in tumor cell growth, and, most notably, as inhibitors of human tumor cell proliferation. As compared to indirubins bearing identical substituents but no hetero atoms in position 7 and 7', the activity of the compounds according to the present invention is increased and the propensity to get metabolized by CYP450s is reduced, resulting in improved metabolic stability.

  本发明涉及7-azaindirubins（1）、7'-azaindirubins（2）和7,7'-二氮杂吲哚（3），其中E、R1和R2的含义在描述中有详细说明，它们的制备和用作治疗癌症、神经退行性疾病、躁郁症、炎症和传染病，包括病毒性疾病的药物。根据结构的不同，这些吲哚作为抑制与肿瘤细胞生长有关的各种激酶的作用，尤其是作为人类肿瘤细胞增殖的抑制剂。与携带相同取代基但在位置7和7'没有杂原子的吲哚相比，根据本发明的化合物的活性增加，且通过CYP450酶代谢的倾向减少，从而提高了代谢稳定性。
• Desarbre E., Merour J. Y., Tetrahedron Lett, 35 (1994) N 13, S 1995-1998
  作者：Desarbre E., Merour J. Y.

  DOI：——

  日期：——
• 7-AZAINDIRUBINS, 7'-AZAINDIRUBINS, 7-7'-DIAZAINDIRUBIN AND THE CORRESPONDING 3'-OXIME ETHER DERIVATES: PRODUCTION THEREOF, THEIR PRODUCTION AND USE AS A MEDICAMENT
  申请人：Eisenbrand, Gerhard

  公开号：EP2379549B1

  公开（公告）日：2016-09-21