ethyl 2-amino-4-(3-nitrophenyl)thiophene-3-carboxylate | 433701-34-9

• 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-amino-4-(3-nitrophenyl)thiophene-3-carboxylate
• CAS: 433701-34-9
• 化学式: C₁₃H₁₂N₂O₄S
• 分子量: 292.315
• InChiKey: DLLNLXISNQAKJZ-UHFFFAOYSA-N

物化性质

• 沸点：
  460.1±45.0 °C(Predicted)
• 密度：
  1.374±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-amino-4-(3-nitrophenyl)thiophene-3-carboxylate 在 盐酸 、 4-二甲氨基吡啶 、 tin(II) chloride dihdyrate 、 sodium methylate 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium iodide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  3-甲基-5-苯基噻吩并[2,3-d]嘧啶-2,4（1H，3H）-二酮衍生物的合成和生物学评价用于治疗饮食性肥胖。

  摘要：

  甘油三酸酯是肝细胞中脂肪的主要部分和一半的脂质，在代谢中起着重要的作用，它是膳食脂肪的能量来源和转运体。在这项研究中，合成了33种基于3-甲基-5-苯基硫代[2,3-d]嘧啶-2,4（1H，3H）-二酮的衍生物，并评估了它们的降脂活性。其中，发现化合物1i在3T3-L1脂肪细胞中具有有效的降低甘油三酸酯的功效，与腺苷单磷酸激活的蛋白激酶（AMPK）激动剂Acadesine（AIACR）相当。此外，以50 mg kg（-1）d（-1）的剂量口服1i 5周可分别使平均体重和肝脏重量降低12.02％和32.00％，并调节血清甘油三酯水平。饮食诱导的肥胖小鼠。

  DOI：

  10.1248/cpb.c14-00258
• 作为产物：
  描述：

  氰乙酸乙酯 、 间硝基苯乙酮 在 吗啉 、 aluminum oxide 、 sulfur 作用下， 反应 0.25h， 生成 ethyl 2-amino-4-(3-nitrophenyl)thiophene-3-carboxylate
  参考文献：
  名称：

  2-(3,4-Dihydro-4-Oxothieno[2,3-d]pyrimidin-2-ylthio) Acetamides as a New Class of Falcipain-2 Inhibitors. 3. Design, Synthesis and Biological Evaluation

  摘要：

  恶性疟原虫 (Plasmodium falciparum) 半胱氨酸蛋白酶 (falcipain-2， FP-2) 是原生质型疟原虫的主要半胱氨酸蛋白酶和必须的血红蛋白酶，这使得它成为研制抗疟药物的一个有吸引力的靶标酶。在本研究中，我们基于用酶抑制法结合基于结构的虚拟筛选得到的化合物 1，设计并合成了系列新型小分子 FP-2 抑制剂。所有化合物均为 FP-2的高效抑制剂，其半抑制浓度 (IC50) 值范围为 1.46 至 11.38 μM，化合物 2a 的抑制活性是母体化合物 1 的 2倍左右。本研究概括总结的初步构效关系将有助于未来抑制剂的设计，这里展示的新骨架以其对 FP-2的强效抑制活性，在发现新型抗疟药物方面也具有潜在的应用价值。

  DOI：

  10.3390/molecules14020785

文献信息

• Aryl Alkyl Ketones in a One-Pot Gewald Synthesis of 2-Aminothiophenes
  作者：Victor Tormyshev、Anthony Flinn、Dmitry Trukhin、Olga Rogozhnikova、Tatiana Mikhalina、Tatiana Troitskaya

  DOI：10.1055/s-2006-951484

  日期：2006.9

  2-Aminothiophene-3-carboxylates bearing various aryl groups at the 4-position are readily obtained in good to moderate yields by the one-pot Gewald reaction of aryl alkyl ketones with ethyl cyanoacetate and elemental sulfur in the presence of morpholinium acetate and excess morpholine.

  通过芳基烷基酮与氰基乙酸乙酯和元素硫在乙酸吗啉和过量吗啉存在下的一锅 Gewald 反应，在 4-位带有各种芳基的 2-氨基噻吩-3-羧酸盐很容易以良好到中等的产率获得.
• Discovery of a Furanopyrimidine-Based Epidermal Growth Factor Receptor Inhibitor (DBPR112) as a Clinical Candidate for the Treatment of Non-Small Cell Lung Cancer
  作者：Shu-Yu Lin、Yung Chang Hsu、Yi-Hui Peng、Yi-Yu Ke、Wen-Hsing Lin、Hsu-Yi Sun、Hui-Yi Shiao、Fu-Ming Kuo、Pei-Yi Chen、Tzu-Wen Lien、Chun-Hwa Chen、Chang-Ying Chu、Sing-Yi Wang、Kai-Chia Yeh、Ching-Ping Chen、Tsu-An Hsu、Su-Ying Wu、Teng-Kuang Yeh、Chiung-Tong Chen、Hsing-Pang Hsieh

  DOI：10.1021/acs.jmedchem.9b00722

  日期：2019.11.27

  Epidermal growth factor receptor (EGFR)-targeted therapy in non-small cell lung cancer represents a breakthrough in the field of precision medicine. Previously, we have identified a lead compound, furanopyrimidine 2, which contains a (S)-2-phenylglycinol structure as a key fragment to inhibit EGFR However, compound 2 showed high clearance and poor oral bioavailability in its pharmacokinetics studies. In this work, we optimized compound 2 by scaffold hopping and exploiting the potent inhibitory activity of various warhead groups to obtain a clinical candidate, 78 (DBPR112), which not only displayed a potent inhibitory activity against EGFR(L858R/T790M) double mutations but also exhibited tenfold potency better than the third-generation inhibitor, osimertinib, against EGFR and HER2 exon 20 insertion mutations. Overall, pharmacokinetic improvement through lead-to-candidate optimization yielded fourfold oral AUC better that afatinib along with F = 41.5%, an encouraging safety profile, and significant antitumor efficacy in in vivo xenograft models. DBPR112 is currently undergoing phase 1 clinical trial in Taiwan.
• [EN] THIOPHENE-BASED COMPOUNDS EXHIBITING ATP-UTILIZING ENZYME INHIBITORY ACTIVITY, AND COMPOSITIONS, AND USES THEREOF<br/>[FR] COMPOSES A BASE DE THIOPHENE PRESENTANT UNE ACTIVITE D'INHIBITION D'ENZYMES UTILISANT L'ATP, COMPOSITIONS CONTENANT CES COMPOSES ET UTILISATIONS
  申请人：AMPHORA DISCOVERY CORP

  公开号：WO2005033102A2

  公开（公告）日：2005-04-14

  Thiophene-based compounds of formula (I) exhibiting ATP-utilizing enzyme inhibitory activity, methods of using compounds exhibiting ATP-utilizing enzyme inhibitory activity, and compositions comprising compounds exhibiting ATP-utilizing enzyme inhibitory activity, are disclosed. These compounds are useful in the treatment of Alzheimer’s disease, stroke, diabetes, obesity, inflammation and cancer.
• 2-(3,4-Dihydro-4-Oxothieno[2,3-d]pyrimidin-2-ylthio) Acetamides as a New Class of Falcipain-2 Inhibitors. 3. Design, Synthesis and Biological Evaluation
  作者：Jin Zhu、Tong Chen、Jie Liu、Ruoqun Ma、Weiqiang Lu、Jin Huang、Honglin Li、Jian Li、Hualiang Jiang

  DOI：10.3390/molecules14020785

  日期：——

  The cysteine protease falcipain-2 (FP-2) of Plasmodium falciparum is a principal cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites, making it become an attractive target enzyme for developing anti-malarial drugs. In this study, a series of novel small molecule FP-2 inhibitors have been designed and synthesized based on compound 1, which was identified by using structure-based virtual screening in conjunction with an enzyme inhibition assay. All compounds showed high inhibitory effect against FP-2 with IC50s of 1.46-11.38 μM, and the inhibitory activity of compound 2a was ~2 times greater than that of prototype compound 1. The preliminary SARs are summarized and should be helpful for future inhibitor design, and the novel scaffold presented here, with its potent inhibitory activity against FP-2, also has potential application in discovery of new anti-malarial drugs.

  恶性疟原虫 (Plasmodium falciparum) 半胱氨酸蛋白酶 (falcipain-2， FP-2) 是原生质型疟原虫的主要半胱氨酸蛋白酶和必须的血红蛋白酶，这使得它成为研制抗疟药物的一个有吸引力的靶标酶。在本研究中，我们基于用酶抑制法结合基于结构的虚拟筛选得到的化合物 1，设计并合成了系列新型小分子 FP-2 抑制剂。所有化合物均为 FP-2的高效抑制剂，其半抑制浓度 (IC50) 值范围为 1.46 至 11.38 μM，化合物 2a 的抑制活性是母体化合物 1 的 2倍左右。本研究概括总结的初步构效关系将有助于未来抑制剂的设计，这里展示的新骨架以其对 FP-2的强效抑制活性，在发现新型抗疟药物方面也具有潜在的应用价值。
• Synthesis and Biological Evaluation of 3-Methyl-5-phenylthieno[2,3-&lt;i&gt;d&lt;/i&gt;]pyrimidine-2,4(1&lt;i&gt;H&lt;/i&gt;,3&lt;i&gt;H&lt;/i&gt;)-dione Derivatives for the Treatment of Diet-Induced Obesity
  作者：Yun Sang、Heyin Pei、Liang Ma、Li Huang、Caifeng Xie、Jinying Chen、Xiaolin Liang、Yan Ran、Guangcheng Wang、Zhuang Yang、Dong Cao、Lin He、Yuzhe Wu、Linhong He、Jun Zhu、Jingbo Lan、Lijuan Chen

  DOI：10.1248/cpb.c14-00258

  日期：——

  of the lipids in hepatocytes, and play an important role in metabolism as energy sources and transporters of dietary fat. In this study, 33 derivatives based on 3-methyl-5-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione were synthesized and evaluated for their lipid-lowering activity. Among them, compound 1i was found to exhibit potent triglyceride-lowering potency in 3T3-L1 adipocytes which was comparable

  甘油三酸酯是肝细胞中脂肪的主要部分和一半的脂质，在代谢中起着重要的作用，它是膳食脂肪的能量来源和转运体。在这项研究中，合成了33种基于3-甲基-5-苯基硫代[2,3-d]嘧啶-2,4（1H，3H）-二酮的衍生物，并评估了它们的降脂活性。其中，发现化合物1i在3T3-L1脂肪细胞中具有有效的降低甘油三酸酯的功效，与腺苷单磷酸激活的蛋白激酶（AMPK）激动剂Acadesine（AIACR）相当。此外，以50 mg kg（-1）d（-1）的剂量口服1i 5周可分别使平均体重和肝脏重量降低12.02％和32.00％，并调节血清甘油三酯水平。饮食诱导的肥胖小鼠。