卡维地洛杂质COH | 51997-50-3

• 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
• 中文名称: 卡维地洛杂质COH
• 英文名称: 3-(oxiran-2-ylmethoxy)-9H-carbazole
• CAS: 51997-50-3
• 化学式: C₁₅H₁₃NO₂
• 分子量: 239.274
• InChiKey: WXRASJNZZKLKBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 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：

  卡维地洛杂质COH 在 三乙胺 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 24.08h， 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：

  9H-咔唑-3-醇 、 环氧溴丙烷 在 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 生成 卡维地洛杂质COH
  参考文献：
  名称：

  [EN] STORE OVERLOAD-INDUCED CALCIUM RELEASE INHIBITORS AND METHODS FOR PRODUCING AND USING THE SAME
  [FR] INHIBITEURS DE LIBÉRATION DU CALCIUM INDUITE PAR UNE SURCHARGE DU STOCK CALCIQUE ET LEURS MÉTHODES DE PRODUCTION ET D'UTILISATION

  摘要：

  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。

  公开号：

  WO2015031914A1

文献信息

• Synthesis of carbonates from CO ₂ and epoxides catalyzed by the system of <i>N</i> ‐heterocyclic carbene, hydrogen bond donor, CrCl ₂ , and tetrabutylammonium bromide
  作者：Kuikui Zhang、Zhenbang Liu、Ning Liu

  DOI：10.1002/aoc.6347

  日期：2021.10

  pyrazole nitrogen bearing benzimidazolium salts was employed as hydrogen bond donor, TBAB was used as nucleophilic reagent, respectively. Under mild conditions (50°C and 1 bar CO2), the terminal epoxides displayed high reactivity in the three-component catalytic system. The catalytic system showed also high catalytic activity for the internal epoxides by increasing the temperature and CO2 pressure and/or

  开发了包括吡啶桥联苯并咪唑鎓盐、CrCl 2和四丁基溴化铵（TBAB）的三组分催化体系。基于对照实验和光谱测量，阐明了三种组分在催化过程中的作用，其中苯并咪唑盐用作N-杂环卡宾前体，一种由 CrCl 2与吡啶氮配位生成的新 Cr 配合物和分别采用含吡唑氮的苯并咪唑盐作为氢键供体，TBAB作为亲核试剂。在温和条件下（50°C 和 1 bar CO 2)，末端环氧化物在三组分催化体系中表现出高反应性。通过提高温度和CO 2压力和/或延长反应时间，催化体系对内环氧化物也显示出高催化活性。
• Novel Carvedilol Analogues That Suppress Store-Overload-Induced Ca²⁺ Release
  作者：Chris D. Smith、Aixia Wang、Kannan Vembaiyan、Jingqun Zhang、Cuihong Xie、Qiang Zhou、Guogen Wu、S. R. Wayne Chen、Thomas G. Back

  DOI：10.1021/jm401090a

  日期：2013.11.14

  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.
• [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。