tert-butyl 4-(7-hydroxy-2-oxo-2H-chromene-3-carbonyl)piperazine-1-carboxylate | 1246818-97-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: tert-butyl 4-(7-hydroxy-2-oxo-2H-chromene-3-carbonyl)piperazine-1-carboxylate
• 英文别名: tert-butyl 4-(7-hydroxy-2-oxochromene-3-carbonyl)piperazine-1-carboxylate
• CAS: 1246818-97-2
• 化学式: C₁₉H₂₂N₂O₆
• 分子量: 374.393
• InChiKey: MSZPCQMOBFRXGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  96.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(7-hydroxy-2-oxo-2H-chromene-3-carbonyl)piperazine-1-carboxylate 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 8.5h， 生成
  参考文献：
  名称：

  硫化氢双发射荧光增强探针及其在生物成像中的应用

  摘要：

  硫化氢 (H 2 S) 是一种新兴的气体递质，可调节多种生理和病理过程。在此，我们报道了一种用于检测生物H 2 S的双发射荧光增强探针DCH-S。该探针由香豆素-SBD 杂化物和2,4-二硝基苯磺酸盐(DNBS) 识别基团组成。响应H 2 S，DCH-S迅速转变为DCH，消除了DNBS基团，然后在456 nm和600 nm处均表现出荧光增强。荧光强度在 5 分钟内达到平台，检测限计算为 47 nM。DCH-S与其他相关分析物相比，对 H 2 S具有高选择性和抗干扰能力。还发现DCH-S在 5-9 的宽 pH 范围内有效发挥作用，并对活的 MCF-7 细胞表现出低毒性。更重要的是，DCH-S成功应用于通过双通道成像检测活细胞和斑马鱼中的外源/内源H 2 S。

  DOI：

  10.1039/d2nj01195f
• 作为产物：
  描述：

  7-羟基香豆素-3-羧酸 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 20.0h， 生成 tert-butyl 4-(7-hydroxy-2-oxo-2H-chromene-3-carbonyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Structure–Activity Relationships of Potent, Targeted Covalent Inhibitors That Abolish Both the Transamidation and GTP Binding Activities of Human Tissue Transglutaminase

  摘要：

  Human tissue transglutaminase (hTG2) is a multifunctional enzyme. It is primarily known for its calcium dependent transamidation activity that leads to formation of an isopeptide bond between glutamine and lysine residues found on the surface of proteins, but it is also a GTP binding protein. Overexpression and unregulated hTG2 activity have been associated with numerous human diseases, including cancer stem cell survival and metastatic phenotype. Herein, we present a series of targeted covalent inhibitors (TCIs) based on our previously reported Cbz-Lys scaffold. From this structure activity relationship (SAR) study, novel irreversible inhibitors were identified that block the transamidation activity of hTG2 and allosterically abolish its GTP binding ability with a high degree of selectivity and efficiency (k(inact)/K-I > 10(5) M-1 min(-1)). One optimized inhibitor (VA4) was also shown to inhibit epidermal cancer stem cell invasion with an EC50 of 3.9 mu M, representing a significant improvement over our previously reported "hit" NC9.

  DOI：

  10.1021/acs.jmedchem.7b01070

文献信息

• [EN] TG2 INHIBITOR COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS INHIBITEURS DE TG2 ET UTILISATIONS DE CES DERNIERS
  申请人：UNIV OTTAWA

  公开号：WO2017179018A1

  公开（公告）日：2017-10-19

  There are provided Tissue Transglutaminase (TG2) inhibitor compounds, and compositions and methods of use thereof for the prevention or treatment of a cancer. Compounds of Formula I, and pharmaceutically acceptable salts thereof, are provided: Formula (I).

  提供了组织转谷氨酰胺酶（TG2）抑制剂化合物，以及其用于预防或治疗癌症的组合物和使用方法。提供了化合物I的公式，以及其药用盐：公式（I）。
• A dual-site controlled fluorescent sensor for the facile and fast detection of H₂O in D₂O by two turn-on emission signals
  作者：Baoli Dong、Yaru Lu、Wenhui Song、Xiuqi Kong、Yaru Sun、Weiying Lin

  DOI：10.1039/c9cc09268d

  日期：——

  A dual-site controlled fluorescent sensor based on FRET mechanism was constructed for the facile and fast detection of H₂O content in D₂O.

  基于FRET机制构建了一种双位点受控荧光传感器，用于快速检测D₂O中H₂O含量。
• A FRET–ICT dual-quenching fluorescent probe with large off–on response for H₂S: synthesis, spectra and bioimaging
  作者：Changyu Zhang、Lv Wei、Chao Wei、Jie Zhang、Runyu Wang、Zhen Xi、Long Yi

  DOI：10.1039/c5cc01184a

  日期：——

  A FRET–ICT dual-quenching fluorescent probe with significant off–on response toward H₂S is rationally designed and prepared for imaging of H₂S in living cells.

  一种具有显著开关响应的FRET-ICT双猝灭荧光探针被合理设计和制备，用于在活细胞中成像H₂S。
• Selective tracking of ovarian-cancer-specific γ-glutamyltranspeptidase using a ratiometric two-photon fluorescent probe
  作者：Ben Shi、Zhenyu Zhang、Qingqing Jin、Zhiqiang Wang、Jie Tang、Ge Xu、Tianli Zhu、Xueqing Gong、Xinjing Tang、Chunchang Zhao

  DOI：10.1039/c8tb01735b

  日期：——

  accurate prediction of cancer diagnosis and management. Here, we report the two-photon ratiometric tracking of GGT activity in cancer cells based on a probe with switchable Förster resonance energy transfer properties. In the absence of GGT, the designed probe showed two well-resolved emission bands at 461 and 610 nm, corresponding to the 7-hydroxycoumarin donor and BODIPY acceptor, respectively. In contrast

  实时跟踪人类卵巢癌细胞中GGT酶活性是准确预测癌症诊断和管理的可靠方法。在这里，我们报告了基于具有可切换Förster共振能量转移特性的探针的癌细胞中GGT活性的双光子比率跟踪。在没有GGT的情况下，设计的探针在461和610 nm处显示出两个分辨良好的发射带，分别对应于7-羟基香豆素供体和BODIPY受体。相比之下，GGT催化的级联反应包括γ-谷氨酰基的裂解以及随后的芳烃从S原子转移到N原子增加了两个发色团之间的距离，从而降低了FRET效率，并在461 nm处恢复了供体荧光。 。通过利用这种酶触发的比例测量，
• Dual Site-Controlled and Lysosome-Targeted Intramolecular Charge Transfer–Photoinduced Electron Transfer–Fluorescence Resonance Energy Transfer Fluorescent Probe for Monitoring pH Changes in Living Cells
  作者：Baoli Dong、Xuezhen Song、Chao Wang、Xiuqi Kong、Yonghe Tang、Weiying Lin

  DOI：10.1021/acs.analchem.6b00422

  日期：2016.4.5

  critical physiological factor for controlling the activities and functions of lysosome. Herein, we report a novel dual site-controlled and lysosome-targeted intramolecular charge transfer–photoinduced electron transfer–Fluorescence resonance energy transfer (ICT–PET–FRET) fluorescent probe (CN-pH), which was essentially the combination of a turn-on pH probe (CN-1) and a turn-off pH probe (CN-2) by a nonconjugated

  酸性pH是控制溶酶体活性和功能的关键生理因素。在此，我们报道了一种新型的双位点控制和溶酶体靶向的分子内电荷转移-光诱导的电子转移-荧光共振能量转移（ICT-PET-FRET）荧光探针（CN-pH），其本质上是转通过非共轭接头在pH探针（CN-1）上关闭pH探针（CN-2）。选择香豆素和萘二甲酰亚胺荧光团作为供体和受体来构建FRET平台。羟基和吗啉同时用作两个pH传感位点，并分别通过ICT和PET控制香豆素和萘二甲酰亚胺单元的荧光。CN-pH对pH的传感机制本质上是ICT，PET和FRET过程的集成。同时，吗啉还可以作为靶向溶酶体的基团。通过将两种排放强度之比的两种数据分析方法结合起来（R）和反比R '（R '= 1 / R），CN-pH的荧光比可以在pH 4.0至8.0的很宽的范围内显示与pH值成比例的关系，并且灵敏度很高。该探针已成功应用于溶酶体pH值的荧光成像，以及按比例显示活细胞中氯