(11bR)-1,6,7,11b-tetrahydro-9,10-dimethoxy-3-(2-methylpropyl)-4H-benzo[a]quinolizine | 920265-21-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (11bR)-1,6,7,11b-tetrahydro-9,10-dimethoxy-3-(2-methylpropyl)-4H-benzo[a]quinolizine
• 英文别名: (11bR)-9,10-dimethoxy-3-(2-methylpropyl)-4,6,7,11b-tetrahydro-1H-benzo[a]quinolizine
• CAS: 920265-21-0
• 化学式: C₁₉H₂₇NO₂
• 分子量: 301.429
• InChiKey: VHLATFMZPWYSEZ-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (11bR)-1,6,7,11b-tetrahydro-9,10-dimethoxy-3-(2-methylpropyl)-4H-benzo[a]quinolizine 在 高氯酸 、 dimethyl sulfide borane 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 86.5h， 生成 (2R,3S,11bR)-1,3,4,6,7,11b-hexahydro-9,10-methoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-ol
  参考文献：
  名称：

  Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors

  摘要：

  Tetrabenazine (TBZ) ((+/-)-1) and dihydrotetrabenazines (DHTBZ) are potent inhibitors of VMAT2. Herein, a practical chemical resolution of (+/-)-1 and stereoselective synthesis of all eight DHTBZ stereoisomers are described. The result of VMAT2 binding assay revealed that (+)-1 (K-i = 4.47 nM) was 8000-fold more potent than ()-1 (K-i = 36,400 nM). Among all eight DHTBZ stereoisomers, (2R,3R,11bR)-DHTBZ ((+)-2: K-i= 3.96 nM) showed the greatest affinity for VMAT2. The (3R,11bR)-configuration appeared to play a key role for VMAT2 binding. In summary, (+)-1, (+)-2, and their derivatives warrant further studies in order to develop more potent and safer drugs for the treatment of chorea associated with Huntington's disease and other hyperkinetic disorders. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.046
• 作为产物：
  描述：

  丁苯那嗪 在 sodium tetrahydroborate 、 五氯化磷 、 D(+)-10-樟脑磺酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 0.5h， 生成 (11bR)-1,6,7,11b-tetrahydro-9,10-dimethoxy-3-(2-methylpropyl)-4H-benzo[a]quinolizine
  参考文献：
  名称：

  Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors

  摘要：

  Tetrabenazine (TBZ) ((+/-)-1) and dihydrotetrabenazines (DHTBZ) are potent inhibitors of VMAT2. Herein, a practical chemical resolution of (+/-)-1 and stereoselective synthesis of all eight DHTBZ stereoisomers are described. The result of VMAT2 binding assay revealed that (+)-1 (K-i = 4.47 nM) was 8000-fold more potent than ()-1 (K-i = 36,400 nM). Among all eight DHTBZ stereoisomers, (2R,3R,11bR)-DHTBZ ((+)-2: K-i= 3.96 nM) showed the greatest affinity for VMAT2. The (3R,11bR)-configuration appeared to play a key role for VMAT2 binding. In summary, (+)-1, (+)-2, and their derivatives warrant further studies in order to develop more potent and safer drugs for the treatment of chorea associated with Huntington's disease and other hyperkinetic disorders. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.046

文献信息

• WO2007/17654
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2007/7105
  申请人：——

  公开号：——

  公开（公告）日：——
• Dihydrotetrabenazines And Pharmaceutical Compositions Containing Them
  申请人：Tridgett Robert

  公开号：US20080108645A1

  公开（公告）日：2008-05-08

  The invention provides novel isomers of dihydrotetrabenazine, individual enantiomers and mixtures thereof wherein the dihydrotetrabenazine is a 3,11 b-cis-dihydrotetrabenazine. Also provided are methods for the preparation of the novel isomers, pharmaceutical compositions containing them and their use in treating hyperkinetic movement disorders such as Huntington's disease, hemiballismus, senile chorea, tic, tardive dyskinesia and Tourette's syndrome.
• Use of 3,1IB-Cis-Dihydrotetrabenazine for the Treatment of Symptoms of Huntingtons Disease
  申请人：Tridgett Robert

  公开号：US20080319000A1

  公开（公告）日：2008-12-25

  The invention provides 3,11b-cis-dihydrotetrabenazine for use in halting or slowing the progress of one or more symptoms of Huntington's disease in a patient, and more particularly a symptom selected from involuntary movements such as involuntary chorea, tremors and twitches, and degeneration in gait.
• 3,11 b-cis-Dihydrotetrabenazine for the Treatment of a Proliferative Disease or an Inflammatory Disease
  申请人：Duffield Andrew John

  公开号：US20090275605A1

  公开（公告）日：2009-11-05

  The invention provides the use of a compound for the manufacture of a medicament for the prophylaxis or treatment of a proliferative disease or an inflammatory disease, the compound being 3,11b-cis-dihydrotetrabenazine or a pharmaceutically acceptable salt thereof.