licarbazepine ethyl carbonate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: licarbazepine ethyl carbonate
• 英文别名: (11-Carbamoyl-5,6-dihydrobenzo[b][1]benzazepin-5-yl) ethyl carbonate
• 化学式: C₁₈H₁₈N₂O₄
• 分子量: 326.352
• InChiKey: BHZJKRIOQCCBIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  奥卡西平 在 吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 licarbazepine ethyl carbonate
  参考文献：
  名称：

  Anticonvulsant and Sodium Channel-Blocking Properties of Novel 10,11-Dihydro-5H-dibenz[b,f]azepine-5-carboxamide Derivatives

  摘要：

  A. series of esters of the major metabolite of oxcarbazepine (2), 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide, were synthesized and evaluated for their anticonvulsant and brain sodium channel-blocking properties. The compounds were assayed intraperitoneally and per os in rats against seizures induced by maximal electroshock (MES). Neurologic deficit was evaluated by the rotarod test. The enantiomeric acetates (R)-11 and (S)-12 were the most active of the series against MES-induced seizures with oral ED50 values at t(max) of 10.9 +/- 2.3 and 4.7 +/- 9 mg/kg, respectively. After intraperitoneal administration, carbamazepine (1) behaved more potently than 2 and all other new dibenz[b,f]azepine-5-carboxamide derivatives in the MES test; compounds 2 and 12 were equally potent. In the rotarod test, low doses of 1. produced considerable motor impairment, which did not occur with 2, enantiomeric alcohols (S)-6;, (R)-7, and racemic alcohol, or racemic acetate 10 or (R)-11. The potencies of the racemic and enantiomerically pure alcohols 8, (S)-6, and (R)-7 derived from 2 in the MES and rotarod test were found to be similar between them, and consequently they exhibit similar protective index values. All three forms of the alcohol and their corresponding acetates (pairs 8 & 10, 6 & 12, and 7 & 11) were found to differ in the MES or rotarod tests; the ED50 value for (S)-6 against MES-induced seizures was nearly 3-fold that for (S)-12. The protective index also differed markedly between all stereoisomers of the alcohol and their corresponding acetates, most pronouncedly for compound (S)-12 which attained the highest value (12.5) among all compounds tested. Blockade of voltage-sensitive sodium channels was studied by investigating [H-3]-batrachotoxinin A 20-alpha-benzoate ([H-3]BTX) binding. Acetates (R)-11 and (S)-12 were more potent than the standards 1 and-2 at inhibiting the binding of [H-3]BTX to sodium channels and the influx: of Na-22(+) into rat brain synaptosomes. It is concluded that acetates (R)-11 and (5)-12 are not simple metabolic precursors of alcohols (R)-7 and (S)-6 in rodents but that they possess anticonvulsant and sodium channel-blocking properties in their own right.

  DOI：

  10.1021/jm980627g

文献信息

• [EN] PROCESS FOR PREPARING (S)-(-)-10-ACETOXY-10,11-DIHYDRO-5H-DIBENZ[B,F]AZEPINE-5-CARBOXAMIDE AND ITS ESTERS THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE (S)-(-)-10-ACÉTOXY-10,11-DIHYDRO-5H-DIBENZ[B,F]AZÉPINE-5-CARBOXAMIDE ET SES ESTERS
  申请人：MATRIX LAB LTD

  公开号：WO2011045648A3

  公开（公告）日：2011-06-09
• Substituted dihydrodibenzo(b,f)azepines, method for their preparation, their use in the treatment of some central nervous system disorders, and pharmaceutical compositions containing them
  申请人：Portela & Ca., S.A.

  公开号：EP0751129B1

  公开（公告）日：1998-11-18
• Anticonvulsant and Sodium Channel-Blocking Properties of Novel 10,11-Dihydro-5<i>H</i>-dibenz[<i>b</i>,<i>f</i>]azepine-5-carboxamide Derivatives
  作者：Jan Benes、António Parada、Anabela A. Figueiredo、Paula C. Alves、Ana P. Freitas、David A. Learmonth、Rodrigo A. Cunha、José Garrett、Patrício Soares-da-Silva

  DOI：10.1021/jm980627g

  日期：1999.7.1

  A. series of esters of the major metabolite of oxcarbazepine (2), 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide, were synthesized and evaluated for their anticonvulsant and brain sodium channel-blocking properties. The compounds were assayed intraperitoneally and per os in rats against seizures induced by maximal electroshock (MES). Neurologic deficit was evaluated by the rotarod test. The enantiomeric acetates (R)-11 and (S)-12 were the most active of the series against MES-induced seizures with oral ED50 values at t(max) of 10.9 +/- 2.3 and 4.7 +/- 9 mg/kg, respectively. After intraperitoneal administration, carbamazepine (1) behaved more potently than 2 and all other new dibenz[b,f]azepine-5-carboxamide derivatives in the MES test; compounds 2 and 12 were equally potent. In the rotarod test, low doses of 1. produced considerable motor impairment, which did not occur with 2, enantiomeric alcohols (S)-6;, (R)-7, and racemic alcohol, or racemic acetate 10 or (R)-11. The potencies of the racemic and enantiomerically pure alcohols 8, (S)-6, and (R)-7 derived from 2 in the MES and rotarod test were found to be similar between them, and consequently they exhibit similar protective index values. All three forms of the alcohol and their corresponding acetates (pairs 8 & 10, 6 & 12, and 7 & 11) were found to differ in the MES or rotarod tests; the ED50 value for (S)-6 against MES-induced seizures was nearly 3-fold that for (S)-12. The protective index also differed markedly between all stereoisomers of the alcohol and their corresponding acetates, most pronouncedly for compound (S)-12 which attained the highest value (12.5) among all compounds tested. Blockade of voltage-sensitive sodium channels was studied by investigating [H-3]-batrachotoxinin A 20-alpha-benzoate ([H-3]BTX) binding. Acetates (R)-11 and (S)-12 were more potent than the standards 1 and-2 at inhibiting the binding of [H-3]BTX to sodium channels and the influx: of Na-22(+) into rat brain synaptosomes. It is concluded that acetates (R)-11 and (5)-12 are not simple metabolic precursors of alcohols (R)-7 and (S)-6 in rodents but that they possess anticonvulsant and sodium channel-blocking properties in their own right.