7-hydroxy-4-(thiophen-2-yl)-2H-chromen-2-one

• 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: 7-hydroxy-4-(thiophen-2-yl)-2H-chromen-2-one
• 英文别名: 7-Hydroxy-4-thiophen-2-ylchromen-2-one；7-hydroxy-4-thiophen-2-ylchromen-2-one
• 化学式: C₁₃H₈O₃S
• 分子量: 244.271
• InChiKey: SBQOATZBNFGODN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-hydroxy-4-(thiophen-2-yl)-2H-chromen-2-one 在 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 、 乙腈 为溶剂， 生成 7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)-4-(thiophen-2-yl)-2H-chromen-2-one
  参考文献：
  名称：

  Synthesis and Biological Investigation of Coumarin Piperazine (Piperidine) Derivatives as Potential Multireceptor Atypical Antipsychotics

  摘要：

  The discovery and synthesis of potential and novel antipsychotic coumarin derivatives, associated with potent dopamine 132, D3, and serotonin S-HT1A and S-HT2A, receptor properties, are the focus of the present article. The most-promising derivative was 7-(4-(4-(6-fluorobenzo[d]-isoxazol-3-yl)-piperidin-1-yl)butoxy)-4-methyl-8-chloro-2H- chromen-2-one (17m). This derivative possesses unique pharmacological features, including high affinity for dopamine D-2 and D-3 and serotonin S-HT1A and 5-HT2A receptors. Moreover, it possesses low affinity for S-HT2C and H-1 receptors (to reduce the risk of obesity associated with chronic treatment) and hERG channels (to reduce the incidence of torsade des pointes). In animal models, compound 17m inhibited apomorphine-induced climbing behavior, MK-801-induced hyperactivity, and the conditioned avoidance response without observable catalepsy at the highest dose tested. Further, fewer preclinical adverse events were noted with 17m compared with risperidone in assays that measured prolactin secretion and weight gain. Acceptable pharmacokinetic properties were also noted with 17m. Taken together, 17m may constitute a novel class of drugs for the treatment of schizophrenia.

  DOI：

  10.1021/jm400408r
• 作为产物：
  描述：

  methyl 2-(7-hydroxy-4-(thiophen-2-yl)-2H-chromen-2-ylidene)acetate 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以45%的产率得到7-hydroxy-4-(thiophen-2-yl)-2H-chromen-2-one
  参考文献：
  名称：

  优先氧气支架合成的面向多样性的通用协议：吡喃酮，香豆素，苯并香豆素和萘香豆素†

  摘要：

  一种新的合成各种功能化特权氧杂环骨架的通用方法，即。开发了吡喃酮，香豆素和苯甲酰香豆素。合成过程是通过碳负离子诱导的内酯与各种亚甲基羰基化合物的环转化，然后由DDQ介导的氧杂亚砜中间体的氧化裂解而实现的。研究在DDQ存在下将草酰亚烷基中间体转化为相应的羰基化合物的机理表明，该反应是通过形成迈克尔加合物而不是分子间电荷转移复合物。该方法提供了对氧杂环分子框架上的许多官能团具有耐受性的多种特权支架的制造。

  DOI：

  10.1039/c3ob40859k

文献信息

• Skeletal diversity construction via a branching synthetic strategy
  作者：Emma E. Wyatt、Suzanne Fergus、Warren R. J. D. Galloway、Andreas Bender、David J. Fox、Alleyn T. Plowright、Alan S. Jessiman、Martin Welch、David R. Spring

  DOI：10.1039/b607710b

  日期：——

  A branching synthetic strategy was used to efficiently generate structurally diverse scaffolds, which span a broad area of chemical descriptor space, and their biological activity against MRSA was demonstrated.

  一种分支合成策略被用来高效生成结构多样的骨架，覆盖了广泛的化学描述空间，并且证明了它们对耐甲氧西林金黄色葡萄球菌（MRSA）的生物活性。
• Discovery of a Novel, Potent, Orally Active, and Safe Inhibitor Targeting Human Mitochondrial RNA Polymerase
  作者：Xinnan Li、Xiaotong Ze、Shengnan Zhou、Zhaoxin Hu、Chen He、Yilin Jia、Lihua Liu、Tao Wang、Junda Li、Shengtao Xu、Dong-Hua Yang、Zhe-Sheng Chen、Hequan Yao、Jinyi Xu、Hong Yao

  DOI：10.1021/acs.jmedchem.3c00058

  日期：——

  depends on OXPHOS for energy supply, particularly in slow-cycling tumor cells. Therefore, targeting human mitochondrial RNA polymerase (POLRMT) to inhibit mitochondrial gene expression emerges as a potential therapeutic strategy to eradicate tumor cells. In this work, exploration and optimization of the first-in-class POLRMT inhibitor IMT1B and its SAR led to the identification of a novel compound D26

  高氧化磷酸化 (OXPHOS) 发生在一些肿瘤中，这依赖于 OXPHOS 的能量供应，特别是在慢循环肿瘤细胞中。因此，靶向人线粒体 RNA 聚合酶 (POLRMT) 以抑制线粒体基因表达成为根除肿瘤细胞的潜在治疗策略。在这项工作中，对一流的 POLRMT 抑制剂 IMT1B 及其 SAR 的探索和优化导致鉴定出一种新型化合物D26，该化合物对多种癌细胞具有强烈的抗增殖作用，并降低线粒体相关基因的表达。此外，机制研究表明D26在 G1 期阻止细胞周期，对 A2780 细胞的细胞凋亡、去极化线粒体或反应性氧化应激的产生没有影响。重要的是，D26在 A2780 异种移植裸鼠中表现出比先导 IMT1B 更有效的抗癌活性，并且没有可观察到的毒性作用。所有结果表明，D26作为一种有效且安全的抗肿瘤候选物值得进一步研究。
• Diversity-oriented general protocol for the synthesis of privileged oxygen scaffolds: pyrones, coumarins, benzocoumarins and naphthocoumarins
  作者：Atul Goel、Gaurav Taneja、Ashutosh Raghuvanshi、Ruchir Kant、Prakas R. Maulik

  DOI：10.1039/c3ob40859k

  日期：——

  A new general methodology for the synthesis of various functionalized privileged oxygen heterocyclic scaffolds, viz. pyrones, coumarins, and benzannulated coumarins, is developed. The synthesis proceeds through carbanion-induced ring transformation of lactones with various methylene carbonyl compounds followed by DDQ-mediated unprecedented oxidative cleavage of oxaylidenes intermediates. Studies of

  一种新的合成各种功能化特权氧杂环骨架的通用方法，即。开发了吡喃酮，香豆素和苯甲酰香豆素。合成过程是通过碳负离子诱导的内酯与各种亚甲基羰基化合物的环转化，然后由DDQ介导的氧杂亚砜中间体的氧化裂解而实现的。研究在DDQ存在下将草酰亚烷基中间体转化为相应的羰基化合物的机理表明，该反应是通过形成迈克尔加合物而不是分子间电荷转移复合物。该方法提供了对氧杂环分子框架上的许多官能团具有耐受性的多种特权支架的制造。
• Synthesis and Biological Investigation of Coumarin Piperazine (Piperidine) Derivatives as Potential Multireceptor Atypical Antipsychotics
  作者：Yin Chen、Songlin Wang、Xiangqing Xu、Xin Liu、Minquan Yu、Song Zhao、Shicheng Liu、Yinli Qiu、Tan Zhang、Bi-Feng Liu、Guisen Zhang

  DOI：10.1021/jm400408r

  日期：2013.6.13

  The discovery and synthesis of potential and novel antipsychotic coumarin derivatives, associated with potent dopamine 132, D3, and serotonin S-HT1A and S-HT2A, receptor properties, are the focus of the present article. The most-promising derivative was 7-(4-(4-(6-fluorobenzo[d]-isoxazol-3-yl)-piperidin-1-yl)butoxy)-4-methyl-8-chloro-2H- chromen-2-one (17m). This derivative possesses unique pharmacological features, including high affinity for dopamine D-2 and D-3 and serotonin S-HT1A and 5-HT2A receptors. Moreover, it possesses low affinity for S-HT2C and H-1 receptors (to reduce the risk of obesity associated with chronic treatment) and hERG channels (to reduce the incidence of torsade des pointes). In animal models, compound 17m inhibited apomorphine-induced climbing behavior, MK-801-induced hyperactivity, and the conditioned avoidance response without observable catalepsy at the highest dose tested. Further, fewer preclinical adverse events were noted with 17m compared with risperidone in assays that measured prolactin secretion and weight gain. Acceptable pharmacokinetic properties were also noted with 17m. Taken together, 17m may constitute a novel class of drugs for the treatment of schizophrenia.