1-(9H-carbazol-1-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]-amino}-2-propanol | 849683-70-1

• 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: 1-(9H-carbazol-1-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]-amino}-2-propanol
• 英文别名: carvedilol；1-(9H-carbazol-1-yloxy)-3-[2-(2-methoxyphenoxy)ethylamino]propan-2-ol
• CAS: 849683-70-1
• 化学式: C₂₄H₂₆N₂O₄
• 分子量: 406.481
• InChiKey: DROFGBXKPGGRDP-UHFFFAOYSA-N

物化性质

• 沸点：
  655.2±55.0 °C(Predicted)
• 密度：
  1.250±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  75.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethyl-4-nitrophenylsulfonium trifluoromethanesulfonate 、 1-(9H-carbazol-1-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]-amino}-2-propanol 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以48%的产率得到3-((9H-carbazol-1-yl)oxy)-N-(2-(2-methoxyphenoxy)ethyl)-2-(4-nitrophenoxy)propan-1-amine
  参考文献：
  名称：

  通过CS键裂解形成无过渡金属的芳基-杂原子键。

  摘要：

  芳基-杂原子键（C-Het）几乎普遍存在于化学分子中。然而，从简单的基底形成各种C-Het键的方法受到限制。在本文中，我们报道了在没有任何过渡金属催化剂的情况下，芳基a便捷，有效的CS键转化为各种C-Het键（CO，CS，C-Sn，C-Si，C-Se）的方法。这些反应在较宽的底物范围内在温和条件下进行。

  DOI：

  10.1021/acs.orglett.9b02584
• 作为产物：
  描述：

  1-羟基咔唑 在 sodium hydroxide 作用下， 以 二甲基亚砜 、 异丙醇 为溶剂， 生成 1-(9H-carbazol-1-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]-amino}-2-propanol
  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

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。
• PROCESS FOR THE PREPARATION OF HIGHLY OPTICAL PURE CARVEDILOL
  申请人：Kim Seong-Jin

  公开号：US20090176992A1

  公开（公告）日：2009-07-09

  The present invention relates to a process for the efficient preparation of highly optical pure chiral carvedilol. According to the present invention, a chiral oxazolidin-2-one or oxazolidin-2-thione having formula 2, produced from the reaction of N-protected 2-(2-methoxyphenoxy)ethylamine with a chiral glycidol derivative is used as a key intermediate for the preparation of the chiral carvedilol. Specifically, the process for the preparation of the chiral carvedilol comprises a) reacting a compound of formula 2 with a halogenation agent, a sulfonation agent or a mitsunobu reagent to activate a hydroxyl group of the compound of formula 2, followed by nucleophilic substitution reaction with 9H-4-hydroxy carbazole to produce a compound of formula 7, and b) subjecting the obtained compound of formula 7 to a deprotection reaction in a presence of an inorganic base to produce the targeted chiral carvedilol. The process of the present invention can be accomplished in a mild condition. The process neither requires any extraordinary purification procedure, nor involves decrease of optical purity. Therefore, the process of the present invention provides highly optical pure chiral carvedilol in simple and efficient manner.

  本发明涉及一种高效制备高度光学纯手性卡维地洛的方法。根据本发明，使用由保护的N-2-(2-甲氧基苯氧基)乙基胺与手性环氧丙醇衍生物反应生成的式2手性噁唑烷-2-酮或噁唑烷-2-硫酮作为制备手性卡维地洛的关键中间体。具体而言，制备手性卡维地洛的过程包括a)将式2化合物与卤化剂、磺化剂或三宅信试剂反应以激活式2化合物的羟基，随后与9H-4-羟基咔唑进行亲核取代反应，生成式7化合物，并b)在无机碱存在下对得到的式7化合物进行去保护反应，生成目标手性卡维地洛。本发明的过程可以在温和条件下完成，既不需要任何特殊的纯化过程，也不涉及光学纯度的降低。因此，本发明的方法以简单高效的方式提供高度光学纯的手性卡维地洛。
• STABILIZED CARVEDILOL INJECTION SOLUTION
  申请人：Roche Diagnostics GmbH

  公开号：EP1098646A1

  公开（公告）日：2001-05-16
• NEW CRYSTALLINE FORMS OF CARVEDILOL
  申请人：KRKA, tovarna zdravil, d.d., Novo mesto

  公开号：EP1660451A2

  公开（公告）日：2006-05-31
• STORE OVERLOAD-INDUCED CALCIUM RELEASE INHIBITORS AND METHODS FOR PRODUCING AND USING THE SAME
  申请人：BACK Tom

  公开号：US20160214973A1

  公开（公告）日：2016-07-28

  The present invention provides compounds having store overload-induced Ca 2+ release (SOICR) inhibitory activity and methods for producing and using the same. In particular, compounds of the invention is of the formula: R 1 —X 1 -L-X 2 —R 2 , wherein R 1 , X 1 , L, X 2 , and R 2 are those defined herein.