2-methoxy-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine | 87747-76-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: 2-methoxy-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine
• 英文别名: 2-methoxy-5-methyl-10,11-dihydro-5H-5,10-epiminodibenzo-[a,d][7]annulene；L-641074；2-methoxy-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine；5-methoxy-1-methyl-16-azatetracyclo[7.6.1.02,7.010,15]hexadeca-2(7),3,5,10,12,14-hexaene
• CAS: 87747-76-0
• 化学式: C₁₇H₁₇NO
• 分子量: 251.328
• InChiKey: PDOAXXWUKAYCDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methoxy-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine 以 甲醇 、 氯仿 、 水 为溶剂， 以1.20 g (47%)的产率得到2-hydroxy-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine
  参考文献：
  名称：

  5-Alkyl or hydroxyalkyl

  摘要：

  5-取代-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺及其衍生物和药用盐可用作抗癫痫药。

  公开号：

  US04399141A1
• 作为产物：
  描述：

  2-methoxydibenzocyclohepten-5-one 在 二氯乙酸 、 盐酸羟胺 、 potassium tert-butylate 、 sodium acetate 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 10.75h， 生成 2-methoxy-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists

  摘要：

  A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested.

  DOI：

  10.1021/jm00164a052

文献信息

• Convergent Strategy to Dizocilpine MK-801 and Derivatives
  作者：K. Harsha Vardhan Reddy、Expédite Yen-Pon、Sylvia Cohen-Kaminsky、Samir Messaoudi、Mouad Alami

  DOI：10.1021/acs.joc.8b00305

  日期：2018.4.6

  Barbier-type reaction to construct the α-branched amine, a selective Heck α-coupling tactic to generate the exocyclic alkene skeleton, and a late-stage intramolecular hydroamination reaction between the exocyclic alkene and the secondary protected amine. The efficacy of this method was demonstrated by the synthesis of two news analogues substituted on the aromatic rings.

  已经完成了MK-801的聚合全合成。关键的合成转化包括构建α-支链胺的多组分Barbier型反应，生成环外烯烃骨架的选择性Heckα-偶联策略以及环外烯烃与仲保护胺之间的后期分子内加氢胺化反应。通过合成两个在芳香环上取代的新闻类似物，证明了该方法的有效性。
• THOMPSON, WAYNE J.;ANDERSON, PAUL S.;BRITCHER, SUSAN F.;LYLE, TERRY A.;TH+, J. MED. CHEM., 33,(1990) N, C. 789-808
  作者：THOMPSON, WAYNE J.、ANDERSON, PAUL S.、BRITCHER, SUSAN F.、LYLE, TERRY A.、TH+

  DOI：——

  日期：——
• US4399141A
  申请人：——

  公开号：US4399141A

  公开（公告）日：1983-08-16
• Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists
  作者：Wayne J. Thompson、Paul S. Anderson、Susan F. Britcher、Terry A. Lyle、J. Eric Thies、Catherine A. Magill、Sandor L. Varga、John E. Schwering、Paulette A. Lyle

  DOI：10.1021/jm00164a052

  日期：1990.2

  A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested.
• 5-Alkyl or hydroxyalkyl
  申请人：Merck & Co., Inc.

  公开号：US04399141A1

  公开（公告）日：1983-08-16

  5-Substituted-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imines, derivatives and pharmaceutically acceptable salts thereof are useful as anticonvulsants.

  5-取代-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺及其衍生物和药用盐可用作抗癫痫药。