2-氨基-3,4-噻吩羧酸-3-乙基-4-甲酯 | 844502-63-2

• 物质功能分类: 有机原料 - 氨基化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 2-氨基-3,4-噻吩羧酸-3-乙基-4-甲酯
• 中文别名: 2-氨基噻吩-3,4-二羧酸3-乙酯4-甲酯
• 英文名称: 3-ethyl 4-methyl 2-aminothiophene-3,4-dicarboxylate
• 英文别名: 3-O-ethyl 4-O-methyl 2-aminothiophene-3,4-dicarboxylate
• CAS: 844502-63-2
• 化学式: C₉H₁₁NO₄S
• 分子量: 229.257
• InChiKey: JPILDOOERAALDC-UHFFFAOYSA-N

物化性质

• 熔点：
  102 °C
• 沸点：
  328℃
• 密度：
  1.321
• 闪点：
  152℃

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-氨基-3,4-噻吩羧酸-3-乙基-4-甲酯 在 titanium(IV) isopropylate 、 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 119.0h， 生成 tert-Butyl 4-[4-({[(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)carbonyl]amino}methyl) benzyl]piperazine-1-carboxylate
  参考文献：
  名称：

  Selective Inhibitors of Bacterial t-RNA-(N¹G37) Methyltransferase (TrmD) That Demonstrate Novel Ordering of the Lid Domain

  摘要：

  The tRNA-(N(1)G37) methyltransferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human orthologue TRM5 and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by X-ray cocrystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA.

  DOI：

  10.1021/jm400718n
• 作为产物：
  描述：

  丙酮酸甲酯 、 氰乙酸乙酯 在 sulfur 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以61.34%的产率得到2-氨基-3,4-噻吩羧酸-3-乙基-4-甲酯
  参考文献：
  名称：

  噻吩并嘧啶酮衍生物通过酪氨酸翻转机制重组活性位点，从而抑制细菌tRNA（Guanine37-N1）-甲基转移酶（TrmD）。

  摘要：

  在原核转录组中> 120个修饰的核糖核苷中，许多tRNA修饰对于细菌存活至关重要，这使其合成酶成为抗生素开发的理想靶标。在这里，我们进行了基于结构的tRNA-（N1G37）甲基转移酶TrmD抑制剂的设计，该酶是许多细菌病原体中必不可少的酶。基于铜绿假单胞菌和结核分枝杆菌的TrmDs的晶体结构，我们合成了一系列对TrmD具有纳摩尔效价的噻吩并嘧啶酮衍生物，并发现了抑制剂结合引发的新型活性位点构象变化。这种酪氨酸翻转机制是在铜绿假单胞菌TrmD中唯一发现的，并使辅酶S-腺苷-1-甲硫氨酸（SAM）以及底物tRNA难以接近该酶。生物物理和生化结构-活性关系研究提供了对噻吩并嘧啶酮作为TrmD抑制剂的潜在作用机理的见解，发现了几种衍生物对革兰氏阳性和分枝杆菌病原体具有活性。这些结果为进一步开发作为抗菌剂的TrmD抑制剂奠定了基础。

  DOI：

  10.1021/acs.jmedchem.9b00582

文献信息

• Thienopyridones as AMPK activators for the treatment of diabetes and obesity
  申请人：Iyengar R. Rajesh

  公开号：US20050038068A1

  公开（公告）日：2005-02-17

  The present invention relates to compounds that activate AMP-activated protein kinase (AMPK), including the preparation of the compounds, compositions containing the compounds and the use of the compounds in the prevention or treatment of disorders such as diabetes, metabolic syndrome, and obesity.

  本发明涉及激活AMP-激活蛋白激酶（AMPK）的化合物，包括制备这些化合物、含有这些化合物的组合物以及利用这些化合物在预防或治疗糖尿病、代谢综合征和肥胖等疾病中的用途。
• Structural Insight into Aggregation and Orientation of TPD-Based Conjugated Polymers for Efficient Charge-Transporting Properties
  作者：Dae-Hee Lim、Yeon-Ju Kim、Yeong-A Kim、Kyoungtae Hwang、Jong-Jin Park、Dong-Yu Kim

  DOI：10.1021/acs.chemmater.8b04605

  日期：2019.7.9

  In this study, we obtained a new structural insight into the charge-transporting properties in TPD-based polymers that cannot be solely explained in terms of the type of orientation. We synthesized two types of copolymers comprising mono-TPD or bis-TPD as the accepting unit. Although the planarity and energy levels are similar with the mono-TPD unit, the aggregation state is quite different, and the X-aggregation tendency seems to be stronger when the bis-TPD unit is incorporated. In the case of TPD1, an effective π–π orbital overlap is found to originate from the H-aggregates, and 3D charge transport pathways are formed with a bimodal orientation of edge-on and face-on, resulting in an efficient charge transportation (1.84 cm2·V–1·s–1 of hole and 0.31 cm2·V–1·s–1 of electron). In contrast, despite the well-aligned edge-on orientation of TPD2, it exhibited a relatively very low mobility and splitted emission characteristics in photoluminescence spectra because of the tilted intermolecular stacking pattern with an X-shape (0.015 cm2·V–1·s–1 for hole and 0.16 cm2·V–1·s–1 for electron). An overall characterization of the semiconducting polymers was performed, and it was found that the type of aggregation in the final thin films, such as H- or X-aggregation, is indeed important and perhaps more important than the orientation to obtain polymers with a high charge carrier mobility.

  在本研究中，我们对基于TPD的聚合物中的电荷传输性质获得了新的结构洞察，这些性质不能仅从取向类型来解释。我们合成了两种类型的共聚物，分别包含单TPD或双TPD作为接受单元。尽管单TPD单元的平面性和能级相似，但其聚集状态有显著差异，且当引入双TPD单元时，X型聚集趋势似乎更强。在TPD1情况下，有效的π-π轨道重叠源自H型聚集，形成了三维电荷传输路径，具有边缘-顶面和顶面-顶面的双峰取向，实现了高效的电荷传输（空穴迁移率为1.84 cm²·V⁻¹·s⁻¹，电子迁移率为0.31 cm²·V⁻¹·s⁻¹）。相比之下，尽管TPD2具有良好的边缘-顶面取向，但由于倾斜的分子间堆积模式呈X形（空穴迁移率为0.015 cm²·V⁻¹·s⁻¹，电子迁移率为0.16 cm²·V⁻¹·s⁻¹），其表现出相对较低的迁移率和光致发光光谱中的分裂发射特性。对半导体聚合物进行了全面的表征，发现最终薄膜中的聚集类型，如H型或X型聚集，确实非常重要，甚至可能比取向更重要，以获得具有高电荷载流子迁移率的聚合物。
• COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF
  申请人：BioTheryX, Inc.

  公开号：US20180170948A1

  公开（公告）日：2018-06-21

  The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CK1α, GSPT1, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.

  本发明提供了调节蛋白功能的化合物，以恢复蛋白稳态，包括细胞因子、CK1α、GSPT1、艾奥洛斯和/或伊卡洛斯活性和细胞间粘附。该发明提供了一种调节蛋白介导的疾病的方法，如细胞因子介导的疾病、障碍、状况或反应。提供了包括与其他细胞因子和炎症介质结合的组合物。提供了治疗、改善或预防与蛋白相关的疾病、障碍或状况的方法，包括与细胞因子相关的疾病、障碍和状况，包括炎症、纤维肌痛、类风湿性关节炎、骨关节炎、强直性脊柱炎、银屑病、银屑病关节炎、炎症性肠病、克罗恩病、溃疡性结肠炎、葡萄膜炎、炎症性肺病、慢性阻塞性肺病、阿尔茨海默病和癌症。
• Thienopyrimidinone Derivatives That Inhibit Bacterial tRNA (Guanine37-<i>N</i>¹)-Methyltransferase (TrmD) by Restructuring the Active Site with a Tyrosine-Flipping Mechanism
  作者：Wenhe Zhong、Kalyan Kumar Pasunooti、Seetharamsing Balamkundu、Yee Hwa Wong、Qianhui Nah、Vinod Gadi、Shanmugavel Gnanakalai、Yok Hian Chionh、Megan E. McBee、Pooja Gopal、Siau Hoi Lim、Nelson Olivier、Ed T. Buurman、Thomas Dick、Chuan Fa Liu、Julien Lescar、Peter C. Dedon

  DOI：10.1021/acs.jmedchem.9b00582

  日期：2019.9.12

  ribonucleosides in the prokaryotic epitranscriptome, many tRNA modifications are critical to bacterial survival, which makes their synthetic enzymes ideal targets for antibiotic development. Here we performed a structure-based design of inhibitors of tRNA-(N1G37) methyltransferase, TrmD, which is an essential enzyme in many bacterial pathogens. On the basis of crystal structures of TrmDs from Pseudomonas aeruginosa

  在原核转录组中> 120个修饰的核糖核苷中，许多tRNA修饰对于细菌存活至关重要，这使其合成酶成为抗生素开发的理想靶标。在这里，我们进行了基于结构的tRNA-（N1G37）甲基转移酶TrmD抑制剂的设计，该酶是许多细菌病原体中必不可少的酶。基于铜绿假单胞菌和结核分枝杆菌的TrmDs的晶体结构，我们合成了一系列对TrmD具有纳摩尔效价的噻吩并嘧啶酮衍生物，并发现了抑制剂结合引发的新型活性位点构象变化。这种酪氨酸翻转机制是在铜绿假单胞菌TrmD中唯一发现的，并使辅酶S-腺苷-1-甲硫氨酸（SAM）以及底物tRNA难以接近该酶。生物物理和生化结构-活性关系研究提供了对噻吩并嘧啶酮作为TrmD抑制剂的潜在作用机理的见解，发现了几种衍生物对革兰氏阳性和分枝杆菌病原体具有活性。这些结果为进一步开发作为抗菌剂的TrmD抑制剂奠定了基础。
• Low-Cost Synthesis and Physical Characterization of Thieno[3,4-<i>c</i>]pyrrole-4,6-dione-Based Polymers
  作者：Philippe Berrouard、Stéphane Dufresne、Agnieszka Pron、Justine Veilleux、Mario Leclerc

  DOI：10.1021/jo301512e

  日期：2012.9.21

  The improved synthesis of thieno[3,4-c]pyrrole-4,6-dione (TPD) monomers, including Gewald thiophene ring formation, a Sandmeyer-type reaction, and neat condensation with an amine, is presented. This protocol enables faster, cheaper, and more efficient preparation of TPD units in comparison to traditional methods. Furthermore, a series of TPD homo- and pseudohomopolymers bearing various alkyl chains

  提出了改进的噻吩并[3,4- c ]吡咯-4,6-二酮（TPD）单体的合成方法，包括Gewald噻吩环形成，Sandmeyer型反应以及与胺的纯净缩合反应。与传统方法相比，该协议可以更快，更便宜，更有效地制备TPD装置。此外，通过直接杂芳基聚合（DHAP）程序合成了一系列带有各种烷基链的TPD均聚物和假均聚物。紫外可见吸收和粉末X射线衍射测量揭示了支链与直链烷基链之比与聚合物的光电特性及其在固态状态下的堆积之间的关系。