(3S,16R)-ethyl apovincaminate | 74924-34-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - Eburnan型生物碱
• 英文名称: (3S,16R)-ethyl apovincaminate
• 英文别名: Ethyl (41S,13AR)-13A-ethyl-2,3,41,5,6,13A-hexahydro-1H-indolo[3,2,1-DE]pyrido[3,2,1-IJ][1,5]naphthyridine-12-carboxylate；ethyl (15R,19S)-15-ethyl-1,11-diazapentacyclo[9.6.2.02,7.08,18.015,19]nonadeca-2,4,6,8(18),16-pentaene-17-carboxylate
• CAS: 74924-34-8
• 化学式: C₂₂H₂₆N₂O₂
• 分子量: 350.461
• InChiKey: DDNCQMVWWZOMLN-IFMALSPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S,16R)-ethyl apovincaminate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 C₂₀H₂₁N₂O₂^(1-)*Na⁽¹⁺⁾
  参考文献：
  名称：

  Synthesis and Evaluation of 2′-Hydroxyethyl trans-Apovincaminate Derivatives as Antioxidant and Cognitive Enhancer Agents

  摘要：

  A series of trans-2'-hydroxyethyl and 2'-acyloxyethyl apovincaminates 4b-f and 7b-f has been synthesized and evaluated for their antioxidant and antiamnesic effects. The new esters were prepared from 4a and 7a ethyl esters or from the corresponding carboxylic acid sodium salt. For starting materials 11a,b, a new stereoselective trans-reduction was elaborated. From the combined results of the data obtained from in vitro and in vivo tests and examination of the metabolism, (3R,16S)-2'-hydroxyethyl apovincaminate (7b, RGH-10885) was identified as the most promising compound, owing to its potent neuroprotective and antiamnesic activities. The in vivo effectiveness of selected compounds on the cognitive functions was studied in a one-trial passive avoidance task and a water-labyrinth test.

  DOI：

  10.1021/jm070618k
• 作为产物：
  描述：

  ethyl (1R,12bS)-1-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine-1-(2'-hydroxyimino)propionate 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 4.0h， 生成 (3S,16R)-ethyl apovincaminate
  参考文献：
  名称：

  Synthesis and Evaluation of 2′-Hydroxyethyl trans-Apovincaminate Derivatives as Antioxidant and Cognitive Enhancer Agents

  摘要：

  A series of trans-2'-hydroxyethyl and 2'-acyloxyethyl apovincaminates 4b-f and 7b-f has been synthesized and evaluated for their antioxidant and antiamnesic effects. The new esters were prepared from 4a and 7a ethyl esters or from the corresponding carboxylic acid sodium salt. For starting materials 11a,b, a new stereoselective trans-reduction was elaborated. From the combined results of the data obtained from in vitro and in vivo tests and examination of the metabolism, (3R,16S)-2'-hydroxyethyl apovincaminate (7b, RGH-10885) was identified as the most promising compound, owing to its potent neuroprotective and antiamnesic activities. The in vivo effectiveness of selected compounds on the cognitive functions was studied in a one-trial passive avoidance task and a water-labyrinth test.

  DOI：

  10.1021/jm070618k

文献信息

• Treatment of synucleinopathies
  申请人：Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE)

  公开号：US10918628B2

  公开（公告）日：2021-02-16

  A modulator of PDE1A and/or PDE1C can be used as a medicament, in particular in the prevention or treatment of synucleinopathies, such as multiple system atrophy, dementia with Lewy bodies, Parkinson's disease, pure autonomic failure, rapid eye movement sleep behavior disorder, inherited synucleinopathies caused by mutations or multiplications of the SNCA gene, or synucleinopathies caused by mutations in other genes including, but not limited to, GBA, LRRK2 and PARK2.

  PDE1A 和/或 PDE1C 的调节剂可用作药物，特别是用于预防或治疗突触核蛋白病，如多发性系统萎缩症、路易体痴呆症、帕金森病、纯自律神经衰竭、快速眼动睡眠行为障碍、由 SNCA 基因突变或增殖引起的遗传性突触核蛋白病，或由其他基因突变引起的突触核蛋白病，包括但不限于 GBA、LRRK2 和 PARK2。
• Czibula, Laszlo; Nemes, Andras; Visky, Gyoergy, Liebigs Annalen der Chemie, 1993, # 3, p. 221 - 230
  作者：Czibula, Laszlo、Nemes, Andras、Visky, Gyoergy、Farkas, Maria、Szombathelyi, Zsolt、et al.

  DOI：——

  日期：——
• SZANTAY, CSABA;SZABO, LAJOS;KALAUS, GYORGY;UREIDL, JANOS;CZIBULA, LASZLO;+
  作者：SZANTAY, CSABA、SZABO, LAJOS、KALAUS, GYORGY、UREIDL, JANOS、CZIBULA, LASZLO、+

  DOI：——

  日期：——
• BENARDELLI, GIOVANNI
  作者：BENARDELLI, GIOVANNI

  DOI：——

  日期：——
• ONO, KEHJITI;KAVAKAMI, XADZIMEH;KATSUBEH, SUMIMOTO
  作者：ONO, KEHJITI、KAVAKAMI, XADZIMEH、KATSUBEH, SUMIMOTO

  DOI：——

  日期：——