2-(oxiran-2-ylmethoxy)-9H-carbazole | 51997-49-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-(oxiran-2-ylmethoxy)-9H-carbazole
• CAS: 51997-49-0
• 化学式: C₁₅H₁₃NO₂
• 分子量: 239.274
• InChiKey: WQUGMHSNHWIBJY-UHFFFAOYSA-N

物化性质

• 沸点：
  464.9±15.0 °C(predicted)
• 密度：
  1.327±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  37.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(oxiran-2-ylmethoxy)-9H-carbazole 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 、 异丙醇 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Novel Carvedilol Analogues That Suppress Store-Overload-Induced Ca²⁺ Release

  摘要：

  Carvedilol is a uniquely effective drug for the treatment of cardiac arrhythmias in patients with heart failure. This activity is in part because of its ability to inhibit store-overload-induced calcium release (SOICR) through the RyR2 channel. We describe the synthesis, characterization, and bioassay of ca. 100 compounds based on the carvedilol motif to identify features that correlate with and optimize SOICR inhibition. A single-cell bioassay was employed on the basis of the RyR2-R4496C mutant HEK-293 cell line in which calcium release from the endoplasmic reticulum through the defective channel was measured. IC50 values for SOICR inhibition were thus obtained. The compounds investigated contained modifications to the three principal subunits of carvedilol, including the carbazole and catechol moieties, as well as the linker chain containing the beta-amino alcohol functionality. The SAR results indicate that significant alterations are tolerated in each of the three subunits.

  DOI：

  10.1021/jm401090a
• 作为产物：
  描述：

  2-羟基咔唑 、 环氧溴丙烷 在 sodium hydroxide 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 16.0h， 以9%的产率得到2-(oxiran-2-ylmethoxy)-9H-carbazole
  参考文献：
  名称：

  新系列卡维地洛衍生物的设计、合成和生物学评估，通过阻断机械电传感器通道保护感觉毛细胞免受氨基糖苷类诱导的损伤。

  摘要：

  氨基糖苷类 (AG) 是用于治疗严重细菌感染的广谱抗生素，但具有限制使用的副作用，包括不可逆的听力损失。在这里，我们评估了卡维地洛在小鼠耳蜗培养和体内斑马鱼试验中的耳保护特性，并研究了它的保护机制，我们发现这可能是由毛细胞的机电传感器 (MET) 通道（主要进入途径）的阻断介导的对于 AG。为了了解卡维地洛的全部耳部保护潜力，制备了一系列 18 种类似物，并评估了它们对 AG 引起的损伤的作用以及它们对 MET 通道的亲和力。发现一种衍生物在耳蜗培养中比卡维地洛本身具有更大的保护作用，并且与 MET 通道的结合更紧密。

  DOI：

  10.1021/acs.jmedchem.8b01325

文献信息

• [EN] STORE OVERLOAD-INDUCED CALCIUM RELEASE INHIBITORS AND METHODS FOR PRODUCING AND USING THE SAME<br/>[FR] INHIBITEURS DE LIBÉRATION DU CALCIUM INDUITE PAR UNE SURCHARGE DU STOCK CALCIQUE ET LEURS MÉTHODES DE PRODUCTION ET D'UTILISATION
  申请人：UTI LIMITED PARTNERSHIP

  公开号：WO2015031914A1

  公开（公告）日：2015-03-05

  The present invention provides compounds having store overload-induced Ca2+ release (SOICR) inhibitory activity and methods for producing and using the same. In particular, compounds of the invention is of the formula: R1-X1-L-X2-R2, wherein R1, X1, L, X2, and R2 are those defined herein.

  本发明提供了具有存储过载诱导的Ca2+释放（SOICR）抑制活性的化合物以及生产和使用这些化合物的方法。特别是，本发明的化合物具有如下通式：R1-X1-L-X2-R2，其中R1、X1、L、X2和R2如本文所定义。
• Cardiotonic Compounds With Inhibitory Activity Against Beta-Adrenergic Receptors And Phosphodiesterase
  申请人：Taylor Malcolm George

  公开号：US20080255134A1

  公开（公告）日：2008-10-16

  The present invention provides compounds of formula (I) possessing inhibitory activity against β adrenergic receptors and phosphodiesterase (PDE), including type 3 phosphodiesterase (PDE-3). The present invention further provides pharmaceutical compositions comprising such compounds, methods of preparing such compounds, and methods of using such compounds for regulating calcium homeostasis, for treating a disease, disorder or condition in which disregulation of calcium homeostasis is implicated and for treating cardiovascular disease, stroke, epilepsy, an ophthalmic disorder or migraine.

  本发明提供了具有抑制β肾上腺素受体和磷酸二酯酶（PDE）活性的式（I）化合物，包括3型磷酸二酯酶（PDE-3）。本发明还提供了包括此类化合物的制药组合物，制备此类化合物的方法，以及使用此类化合物调节钙离子稳态，治疗涉及钙离子稳态失调的疾病、紊乱或状况，以及治疗心血管疾病、中风、癫痫、眼科疾病或偏头痛的方法。
• NaOH/BEt ₃ Catalyzed Regioselective Hydroboration of Epoxides to Secondary Alcohols
  作者：Jiali Wang、Wubin Yao、Dandan Hu、Xinxin Qi、Jun‐Qi Zhang、Hongjun Ren

  DOI：10.1002/ejoc.202200759

  日期：2022.9.20

  Here described an efficient and regioselective hydroboration of epoxides to secondary alcohols, the reaction is catalyzed by a combined NaOH/BEt3 catalyst. Such a transition-metal-free catalytic system is suitable for many halogenated compounds and well-tolerated to olefin group under mild conditions.

  这里描述了环氧化物高效和区域选择性的硼氢化成仲醇，该反应由组合的 NaOH/BEt 3催化剂催化。这种不含过渡金属的催化体系适用于许多卤代化合物，并且在温和条件下对烯烃基团具有良好的耐受性。
• A novel carbazole derivative, MHY407, sensitizes cancer cells to doxorubicin-, etoposide-, and radiation treatment via DNA damage
  作者：Sungpil Yoon、Ju-Hwa Kim、Young Ju Lee、Mee Young Ahn、Gayoung Choi、Won Ki Kim、Zunhua Yang、Hye Jin Lee、Hyung Ryong Moon、Hyung Sik Kim

  DOI：10.1016/j.ejphar.2012.10.001

  日期：2012.12

  In this study, we synthesized a novel carbazole derivative, MHY407, as a sensitizer of cancer cells to increase DNA damage. We then evaluated the anticancer effects of MHY407 and identified the molecular mechanism for the sensitization of breast cancer cell lines. MHY407 significantly increased DNA damage as determined by DNA breakage, levels of damage-responsive proteins, and DNA foci. In addition, MHY407 increased p21 and decreased cyclin D1 protein levels. MHY407 also involved increased cell cycle arrest at the S phase. Furthermore, in doxorubicin and etoposide-treated breast cancer cells, co-treatment with MHY407 reduced cell viability and increased apoptosis. Co-treatment of MHY407 with doxorubicin or etoposide increased DNA damage-related proteins and foci formation, suggesting that increased DNA damage by MHY407 plays an important role in the sensitization. In addition, MHY407 also sensitized the cancer cells to DNA damaging radiation treatment. These results may contribute to the development of MHY407-based treatments for cancer patients receiving DNA-damage therapy. (C) 2012 Elsevier B.V. All rights reserved.
• HAPTENS, TRACERS, IMMUNOGENS AND ANTIBODIES FOR CARBAZOLE AND DIBENZOFURAN DERIVATIVES
  申请人：ABBOTT LABORATORIES

  公开号：EP0708767B1

  公开（公告）日：2001-02-14