4-epoxypropanoxycarbazole | 1430052-93-9

• 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: 4-epoxypropanoxycarbazole
• 英文别名: 2,3-Epoxypropoxy Carbazole；1-(oxiran-2-ylmethoxy)-9H-carbazole
• CAS: 1430052-93-9
• 化学式: C₁₅H₁₃NO₂
• 分子量: 239.274
• InChiKey: VLNNJWRDIPGHBE-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：

  2-甲氧基苯氧基乙胺 、 4-epoxypropanoxycarbazole 以 异丙醇 为溶剂， 以66%的产率得到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
• 作为产物：
  描述：

  1-羟基咔唑 、 环氧溴丙烷 在 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 生成 4-epoxypropanoxycarbazole
  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] PROCESS FOR THE PREPARATION OF CARVEDILOL<br/>[FR] PROCESSUS POUR LA PRÉPARATION DE CARVÉDILOL
  申请人：CIPLA LTD

  公开号：WO2005113502A1

  公开（公告）日：2005-12-01

  A process for the preparation of carvedilol of formula (I) (I) either in enantiomeric substantially pure form, or as an enantiomeric mixture, optionally as a pharmaceutically acceptable salt thereof, which process comprises reacting 2,3-eopxypropoxy carbazole of formula (II) (II) or the R or S enantiomer thereof, with N-[2-(2-methoxy-phenoxy)ethyl]-benzylamine of formula (V) (V) to yield benzyl carvedilol of formula (VI) (VI) which is debenzylated by catalytic hydrogenation to yield carvedilol of formula (I), either in enantiomeric substantially pure form, or as an enantiomeric mixture, and if desired reacting the thus formed carvedilol of formula (I) with an inorganic or organic acid to yield a pharmaceutically acceptable salt thereof, and/or, if desired, separating the enantiomers. The above process is characterised in that reaction of said 2,3-epoxypropoxy carbazole of formula (II) with said N-[2-(2-methoxy-phenoxy)ethyl]-benzylamine of formula (V) is carried out in water as the reaction medium. The present invention further provides carvedilol of formula (I) prepared by a process as described above, and pharmaceutical compositions containing the same and therapeutic uses thereof.

  一种用于制备公式（I）的卡维地洛的方法，该方法可以将其制备为对映异构体基本纯形式，或作为对映异构体混合物，可选地作为其药学上可接受的盐，该方法包括将公式（II）的2,3-环氧丙氧基咔唑或其R或S对映体与公式（V）的N-[2-(2-甲氧基苯氧基)乙基]-苄胺反应，得到公式（VI）的苄基卡维地洛，通过催化氢化脱苄基得到公式（I）的卡维地洛，可以制备为对映异构体基本纯形式，或作为对映异构体混合物，并且如有需要，可以将得到的卡维地洛与无机或有机酸反应以得到其药学上可接受的盐，并/或如有需要，分离对映体。上述方法的特点在于，所述的公式（II）的2,3-环氧丙氧基咔唑与所述的公式（V）的N-[2-(2-甲氧基苯氧基)乙基]-苄胺的反应在水中作为反应介质进行。本发明还提供了通过上述描述的方法制备的公式（I）的卡维地洛，以及含有该化合物的药物组合物和其治疗用途。
• [EN] A PROCESS FOR PREPARATION OF 1-[9H-CARBAZOL-4-YLOXY]- 3-[{2-(2-(-(METHOXY)PHENOXY)-ETHYL}-AMINO]-PROPAN-2-OL<br/>[FR] PROCEDE DE PREPARATION DE 1-[9H-CARBAZOL-4-YLOXY]- 3-[{2-(2-(-(METHOXY)PHENOXY)-ETHYL}-AMINO]-PROPANE-2-OL
  申请人：SUN PHARMACEUTICAL IND LTD

  公开号：WO2004113296A1

  公开（公告）日：2004-12-29

  The present invention provides a process for preparation of 1-[9H-carbazol-4-yloxy]-3-[2-(2-(methoxy)phenoxy)-ethyl}-amino]-propan-2-ol, a compound of formula (1) in racemic form or in the form of optically active R or S enantiomer or its pharmaceutically acceptable salt, comprising, reacting 4-(oxiranylmethoxy)-9H-carbazole, a compound of formula (2) or the R or S enantiomer thereof with a compound of formula (5), wherein R1 is benzyl or substituted benzyl group, in an aprotic organic solvent in presence of a catalyst to obtain a compound of formula (6), or the R or S enantiomer thereof, wherein R1 is as defined above. The resultant compound of formula (6) is subjected to debenzylation reaction by catalytic hydrogenation to obtain the compound of formula (1), if desired converting the resultant compound of formula (1) to a pharmaceutically acceptable salt thereof.

  本发明提供了一种制备1-[9H-咔唑基氧基]-3-[2-(2-(甲氧基)苯氧基)-乙基}-氨基]-丙醇的方法，该化合物的结构式为(1)，可以是拉氏体或光学活性R或S对映体，或其药用可接受的盐形式，包括将4-(环氧甲氧基)-9H-咔唑，结构式为(2)的化合物或其R或S对映体与结构式(5)的化合物反应，其中R1是苄基或取代苄基团，在无水有机溶剂中，在催化剂存在下，得到结构式(6)的化合物，或其R或S对映体，其中R1如上定义。得到的结构式(6)的化合物经过脱苄化反应进行催化氢化，得到结构式(1)的化合物，如果需要，将得到的结构式(1)的化合物转化为其药用可接受的盐形式。
• 一种合成2,3-二氢苯并呋喃类化合物的方法
  申请人：武汉大学

  公开号：CN108329285B

  公开（公告）日：2019-12-10

  本发明提供了一种合成2,3‑二氢苯并呋喃类化合物的方法。本发明先将芳香碘化物、环氧化合物、钯催化剂、膦配体、降冰片烯衍生物一起溶于有机溶剂中，然后在30℃到120℃下搅拌反应，反应后分离提纯，即得到2,3‑二氢苯并呋喃类化合物。该方法可以高效、经济、绿色地合成2,3‑二氢苯并呋喃类化合物。该方法条件温和，底物普适性好，产率高，所制备的2,3‑二氢苯并呋喃类化合物广泛地应用在药物化学和有机化学领域。
• [EN] PROCESS FOR THE PREPARATION OF CARVEDILOL VIA SILYL PROTECTION OF SUBSTITUTED AMINE<br/>[FR] PROCÉDÉ PERMETTANT DE PRÉPARER DU CARVEDILOL PAR PROTECTION SILYLE D'AMINE SUBSTITUÉE
  申请人：CADILA PHARMACEUTICALS LTD

  公开号：WO2009115902A1

  公开（公告）日：2009-09-24

  The invention provides new process for preparing Carvedilol by reaction of 4-(oxiran-2- yl-methoxy)-9H-carbazole and substituted silyl protected 2-(2-methoxy phenoxy)-ethylamine compound to give silyl protected Carvedilol intermediate. The silyl protected Carvedilol intermediate on desilylation gives Carvedilol. The invention also provides a novel substituted silyl protected 2-(2-methoxy phenoxy)-ethylamine as key intermediate for the preparation of Carvedilol.

  该发明提供了一种制备卡维地洛的新工艺，通过4-(环氧丙烷-2-基甲氧基)-9H-咔唑与取代硅烷保护的2-(2-甲氧基苯氧基)-乙胺化合物的反应得到硅烷保护的卡维地洛中间体。对硅烷保护的卡维地洛中间体进行去硅反应得到卡维地洛。该发明还提供了一种新型的取代硅烷保护的2-(2-甲氧基苯氧基)-乙胺作为制备卡维地洛的关键中间体。
• Process for the Preparation of Carvedilol
  申请人：Kankan Rajendra Narayanrao

  公开号：US20080234492A1

  公开（公告）日：2008-09-25

  A process for the preparation of carvedilol of formula (I) (I) either in enantiomeric substantially pure form, or as an enantiomeric mixture, optionally as a pharmaceutically acceptable salt thereof, which process comprises reacting 2,3-eopxypropoxy carbazole of formula (II) (II) or the R or S enantiomer thereof, with N-[2-(2-methoxy-phenoxy)ethyl]-benzylamine of formula (V) (V) to yield benzyl carvedilol of formula (VI) (VI) which is debenzylated by catalytic hydrogenation to yield carvedilol of formula (I), either in enantiomeric substantially pure form, or as an enantiomeric mixture, and if desired reacting the thus formed carvedilol of formula (I) with an inorganic or organic acid to yield a pharmaceutically acceptable salt thereof, and/or, if desired, separating the enantiomers. The above process is characterised in that reaction of said 2,3-epoxypropoxy carbazole of formula (II) with said N-[2-(2-methoxy-phenoxy)ethyl]-benzylamine of formula (V) is carried out in water as the reaction medium. The present invention further provides carvedilol of formula (I) prepared by a process as described above, and pharmaceutical compositions containing the same and therapeutic uses thereof.

  一种制备公式（I）的卡维地洛的方法，其中（I）可以是对映异构体纯形式，也可以是对映异构体混合物，可以是其药学上可接受的盐，该方法包括将公式（II）的2,3-环氧丙氧基咔唑或其R或S对映体与公式（V）的N-[2-(2-甲氧基苯氧基)乙基]-苄胺反应，以得到公式（VI）的苄基卡维地洛，通过催化氢化去苄基，得到公式（I）的卡维地洛，可以是对映异构体纯形式，也可以是对映异构体混合物，如果需要，可以将得到的公式（I）的卡维地洛与无机或有机酸反应，以得到其药学上可接受的盐，并且，如果需要，可以分离对映体。上述方法的特点在于，公式（II）的2,3-环氧丙氧基咔唑与公式（V）的N-[2-(2-甲氧基苯氧基)乙基]-苄胺的反应在水中作为反应介质进行。本发明进一步提供了通过上述方法制备的公式（I）的卡维地洛，以及含有其的药物组合物和其治疗用途。