ethyl 2-(2-(5-chloro-2-nitrophenyl)hydrazono)propanoate | 1579994-92-5

• 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: ethyl 2-(2-(5-chloro-2-nitrophenyl)hydrazono)propanoate
• 英文别名: Ethyl 2-[(5-chloro-2-nitrophenyl)hydrazinylidene]propanoate
• CAS: 1579994-92-5
• 化学式: C₁₁H₁₂ClN₃O₄
• 分子量: 285.687
• InChiKey: PLGFOFDYYQNZLL-UHFFFAOYSA-N

物化性质

• 沸点：
  385.7±52.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  96.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-(2-(5-chloro-2-nitrophenyl)hydrazono)propanoate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 磷酸 、 sodium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 水 、 甲苯 为溶剂， 反应 16.0h， 生成 ethyl 4-(3-nitrophenylamino)-7-nitro-1H-indole-2-carboxylate
  参考文献：
  名称：

  Discovery of N-Arylsulfonyl-Indole-2-Carboxamide Derivatives as Potent, Selective, and Orally Bioavailable Fructose-1,6-Bisphosphatase Inhibitors—Design, Synthesis, In Vivo Glucose Lowering Effects, and X-ray Crystal Complex Analysis

  摘要：

  Liver fructose-1,6-bisphosphatase (FBPase) is a key enzyme in the gluconeogenesis pathway. Inhibiting FBPase activity represents a potential treatment for type 2 diabetes mellitus. A series of novel N-arylsulfonyl-4-arylamino-indole-2-carboxamide derivatives have been disclosed as FBPase inhibitors. Through extensive structure-activity relationship investigations, a promising candidate molecule Cpd118 [sodium (7-chloro-4-((3-methoxyphenyl)amino)-1-methyl-1H-indole-2-carbonyl] [(4-methoxyphenyl)sulfonyl)amide] has been identified with high inhibitory activity against human liver FBPase (IC50, 0.029 +/- 0.006 mu M) and high selectivity relative to the other six AMP-binding enzymes. Importantly, Cpd118 produced significant glucose-lowering effects on both type 2 diabetic KKAy mice and ZDF rats as demonstrated by substantial reductions in the fasting and postprandial blood glucose levels, as well as the HbA1c level. Furthermore, Cpd118 elicited a favorable pharmacokinetic profile with an oral bioavailability of 99.1%. Moreover, the X-ray crystal structure of the Cpd118-FBPase complex was resolved, which revealed a unique binding mode and provided a structural basis for its high potency and selectivity.

  DOI：

  10.1021/acs.jmedchem.0c00726
• 作为产物：
  描述：

  2-硝基-5-氯苯胺 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 4.08h， 生成 ethyl 2-(2-(5-chloro-2-nitrophenyl)hydrazono)propanoate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 7-nitro-1H-indole-2-carboxylic acid derivatives as allosteric inhibitors of fructose-1,6-bisphosphatase

  摘要：

  A series of novel indole derivatives was synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase). Extensive structure-activity relationships were conducted and led to a potent FBPase inhibitor 3.9 with an IC50 of 0.99 mu M. The binding mode of this series of indoles was predicted using CDOCKER algorithm. The results of this research will shed light on the further design and optimization of novel small molecules as FBPase inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.047

文献信息

• N-酰基磺酰胺类FBPase抑制剂、其制备方法、 药物组合物及用途
  申请人：中国医学科学院药物研究所

  公开号：CN107098846B

  公开（公告）日：2020-10-09

  本发明公开了新结构的N‑酰基磺酰胺类FBPase抑制剂、及其制法和药物组合物与用途。具体而言，本发明涉及通式I所示的N‑酰基磺酰胺类FBPase抑制剂，其可药用盐，及其制备方法，含有一个或多个该类化合物的组合物，和该类化合物在制备FBPase抑制剂或治疗FBPase有关的疾病药物中的用途，及在制备预防和/或治疗糖尿病药物中的用途。
• Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as IDO1/TDO dual inhibitors
  作者：Guonan Cui、Fangfang Lai、Xiaoyu Wang、Xiaoguang Chen、Bailing Xu

  DOI：10.1016/j.ejmech.2019.111985

  日期：2020.2

  indole-2-carboxylic acid derivatives were synthesized, and their inhibitory activities against both enzymes along with structure-activity relationships were investigated. As a result, a number of 6-acetamido-indole-2-carboxylic acid derivatives were found to be potent dual inhibitors with IC50 values at low micromolar levels. Among them, compound 9o-1 was the most potent inhibitor with an IC50 value

  吲哚胺 2,3-双加氧酶 1 (IDO1) 和色氨酸 2,3-双加氧酶 (TDO) 参与色氨酸代谢的关键步骤，是肿瘤免疫治疗的潜在新靶点。在这项工作中，合成了多种吲哚-2-羧酸衍生物，并研究了它们对两种酶的抑制活性以及构效关系。结果，发现许多 6-乙酰氨基-吲哚-2-羧酸衍生物是有效的双重抑制剂，在低微摩尔水平下具有 IC50 值。其中，化合物9o-1是最有效的抑制剂，对IDO1的IC50值为1.17 μM，对TDO的IC50值为1.55 μM。此外，由化合物 9p 氧化产生的对苯醌衍生物 9p-O，还鉴定了它对两种酶的强烈抑制作用，IC50 值在两位数纳摩尔水平。使用分子对接和分子动力学模拟，我们预测了 IDO1 和 TDO 结合口袋内此类化合物的结合模式。该结果为进一步优化该系列 IDO1/TDO 双抑制剂的结构提供了见解。