3-butylamino-4-ethoxycyclobut-3-ene-1,2-dione | 163421-03-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-butylamino-4-ethoxycyclobut-3-ene-1,2-dione
• 英文别名: 4-butylamino-3-ethoxycyclobut-3-ene-1,2-dione；3-(Butylamino)-4-ethoxy-3-cyclobutene-1,2-dione；3-(butylamino)-4-ethoxycyclobut-3-ene-1,2-dione
• CAS: 163421-03-2
• 化学式: C₁₀H₁₅NO₃
• 分子量: 197.234
• InChiKey: BVUBBVMEUMOLKA-UHFFFAOYSA-N

物化性质

• 熔点：
  49-50 °C
• 沸点：
  310.5±52.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-butylamino-4-ethoxycyclobut-3-ene-1,2-dione 在 盐酸 、 水 作用下， 以86%的产率得到3-(butylamino)-4-hydroxycyclobut-3-ene-1,2-dione
  参考文献：
  名称：

  方酸酰胺和方酸水解的动力学分析及机理

  摘要：

  方胺和方酸的水解降解，是方酰胺部分水解的产物，已通过紫外光谱在37°C和3-10的pH范围内进行了评估。在这些条件下，这些化合物在很长一段时间（> 100天）内都具有动力学稳定性。在pH> 10，在两个squaramate的squaramate阴离子所示的一阶依赖性和OH的水解- 。在相同的温度和[OH - ]，squaramides的水解通常显示与地层squaramates作为检测反应中间体的双相光谱变化（A→B→C动力学模型）。所测得的速率的第一步骤（ķ 1 ≈10 -4中号-1小号-1）是2-3个数量级比用于第二步骤（更快ķ 2 ≈10 -6中号-1小号-1）。在不同温度下的实验提供激活参数与Δ的值ħ ⧧听，说：9-18千卡摩尔-1和Δ小号⧧听，说：-5至-30 CALķ -1摩尔-1。DFT计算表明，方酸的碱性水解机理与酰胺十分相似。

  DOI：

  10.1021/acs.joc.6b02963
• 作为产物：
  描述：

  正丁胺 、 方酸二乙酯 以 乙腈 为溶剂， 反应 10.0h， 以97%的产率得到3-butylamino-4-ethoxycyclobut-3-ene-1,2-dione
  参考文献：
  名称：

  方酸酰胺和方酸水解的动力学分析及机理

  摘要：

  方胺和方酸的水解降解，是方酰胺部分水解的产物，已通过紫外光谱在37°C和3-10的pH范围内进行了评估。在这些条件下，这些化合物在很长一段时间（> 100天）内都具有动力学稳定性。在pH> 10，在两个squaramate的squaramate阴离子所示的一阶依赖性和OH的水解- 。在相同的温度和[OH - ]，squaramides的水解通常显示与地层squaramates作为检测反应中间体的双相光谱变化（A→B→C动力学模型）。所测得的速率的第一步骤（ķ 1 ≈10 -4中号-1小号-1）是2-3个数量级比用于第二步骤（更快ķ 2 ≈10 -6中号-1小号-1）。在不同温度下的实验提供激活参数与Δ的值ħ ⧧听，说：9-18千卡摩尔-1和Δ小号⧧听，说：-5至-30 CALķ -1摩尔-1。DFT计算表明，方酸的碱性水解机理与酰胺十分相似。

  DOI：

  10.1021/acs.joc.6b02963

文献信息

• Rationally designed squaryldiamides – a novel class of sugar-nucleotide mimics?
  作者：Sven Niewiadomski、Zeenat Beebeejaun、Helen Denton、Terry K. Smith、Richard J. Morris、Gerd K. Wagner

  DOI：10.1039/c004165c

  日期：——

  for the diphosphate group, with the ability to coordinate to a divalent metal, is therefore an important design criteria for the development of sugar-nucleotide mimics. Here, we describe the rational design and synthesis of a novel class of sugar-nucleotide mimics based on a squaryldiamide scaffold, an uncharged phosphate isostere. We demonstrate by comprehensive NMR titration experiments that the new

  糖核苷酸，如 GDP-甘露糖， GDP-岩藻糖 和 UDP-葡萄糖 是重要的生物分子，在碳水化合物和 糖缀合物生物合成、代谢和细胞信号传导。天然存在的糖核苷酸的类似物和模拟物作为化学工具和糖核苷酸依赖性酶（包括糖基转移酶）的抑制剂候选物而受到追捧。许多糖核苷酸通过协调它们的目标糖基转移酶二磷酸盐组为活性位点中的二价金属辅因子。因此，鉴定不带电荷的、化学稳定的二磷酸基团替代物，具有与二价金属配位的能力，因此是开发糖核苷酸模拟物的重要设计标准。在这里，我们描述了基于方酸二酰胺支架的新型糖核苷酸模拟物的合理设计和合成。磷酸盐等排。我们通过全面的 NMR 滴定实验证明，新的糖核苷酸模拟物有效地协调了镁2+，并提供来自与治疗相关的甘露糖基转移酶的生物学研究结果 锥虫布氏锥虫。我们的研究结果表明，方酸二酰胺是开发糖核苷酸模拟物的有前途的模板，并说明方二酰胺基团作为抑制剂设计片段的巨大潜力。
• Synthesis and conformational studies of peptido-squaramide foldable modules: a new class of turn-mimetic compounds
  作者：Luis Martínez、Angel Sampedro、Elena Sanna、Antoni Costa、Carmen Rotger

  DOI：10.1039/c2ob06715c

  日期：——

  The β-turn unit is one of the most important secondary structure elements in proteins. The access to new conformationally controlled foldable modules can afford compounds with interesting bioactivities. Here, we describe a new family of peptido-squaramide foldable modules based on the considerable potential of the squaramide unit as a hydrogen bond donor and acceptor as well as the low rotational barrier of the C–N bond. The conformational analysis by NMR of these modules in chloroform and acetonitrile solution shows that a disecondary squaramide with the 4-aminobutyric acid in one of its substituents can mimic the β-turn structure driven by the formation of an intramolecular hydrogen bonded ten-membered ring. This structure, although flexible, has been successfully combined with dipeptide chains to induce the formation of a hairpin-like structure driven by the formation of several cross-strand intramolecular hydrogen bonds.

  β-转角单元是蛋白质中最重要的一种二级结构元素。具有新型构象控制的折叠模块可赋予化合物有趣的生物活性。在此，我们描述了一系列基于方形酰胺单元作为氢键供体和受体的巨大潜力以及碳氮键的低旋转能垒的肽基方形酰胺折叠模块。通过核磁共振对这些模块在氯仿和丙酮腈溶液中的构象分析表明，一种含有4-氨基丁酸作为其取代基之一的双二级方形酰胺可模拟由形成一个分子内氢键的十元环驱动的β-转角结构。尽管该结构具有柔性，但它已成功地与二肽链结合，通过形成多个跨越链的分子内氢键驱动了形成类似发夹的结构。
• The Role of <i>N</i> -Methyl Squaramides in a Hydrogen-Bonding Strategy to Fold Peptidomimetic Compounds
  作者：Luís Martínez-Crespo、Eduardo C. Escudero-Adán、Antonio Costa、Carmen Rotger

  DOI：10.1002/chem.201803930

  日期：2018.12.3

  in their structure to control their conformational properties. The efficacy of this combination has been evaluated to promote folding in peptide‐like compounds to obtain parallel and antiparallel‐hairpin model compounds in hydrogen‐bonding competitive media. Crystallographic structures of model compounds and conformational studies based on NMR spectroscopic analysis of the squaramido‐peptides confirm

  小肽和拟肽化合物是探测和研究生物系统的有价值的工具。小型合成肽类似物采用由组织化合物结构的结构模块驱动的给定二级结构。其中，β和α转弯模拟物得到了广泛使用。这项工作报告了基于SQ4和SQ5方酸的转向模块，该模块在结构中结合了叔和仲方酰胺键来控制其构象性质。已评估此组合的功效，以促进在氢键竞争性介质中的肽样化合物的折叠，从而获得平行和反平行发夹模型化合物。E，Z构象比仲二酰胺类更重要，因此更适合于控制可折叠拟肽化合物的构象。
• Synthesis and Biological Evaluation of <i>N</i>,<i>N</i>′-Squaramides with High in Vivo Efficacy and Low Toxicity: Toward a Low-Cost Drug against Chagas Disease
  作者：Francisco Olmo、Carmen Rotger、Inmaculada Ramírez-Macías、Luis Martínez、Clotilde Marín、Lucas Carreras、Kristína Urbanová、Manel Vega、Guillermo Chaves-Lemaur、Angel Sampedro、María Jose Rosales、Manuel Sánchez-Moreno、Antonio Costa

  DOI：10.1021/jm4017015

  日期：2014.2.13

  Access to basic drugs is a major issue in developing countries. Chagas disease caused by Trypanosorna cruzi is a paradigmatic example of a chronic disease without an effective treatment. Current treatments based on benznidazole and nifurtimox are expensive, ineffective, and toxic. N,N'-Squaramides are amide-type compounds that feature both hydrogen bond donor and acceptor groups and are capable of multiple interactions with complementary sites. When combined with amine and carboxylic groups, squaramide compounds have increased solubility and therefore make suitable therapeutic agents. In this work, we introduce a group of Lipiriski's rule of five compliant squararnides as candidates for treating Chagas disease. The in vivo studies confirmed the positive expectations arising from the preliminary in vitro studies, revealing compound 17 to be the most effective for both acute and chronic phases. The activity, stability, low cost of starting materials, and straightforward synthesis make amino squaramides appropriate molecules for the development of an affordable anti-Chagasic agent.
• Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists
  作者：Christelle Moreau、Tanja Kirchberger、Joanna M. Swarbrick、Stephen J. Bartlett、Ralf Fliegert、Timur Yorgan、Andreas Bauche、Angelika Harneit、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm401497a

  日期：2013.12.27

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.