3-bromo-10,11-dihydro-5-methyl-5H-dibenzo[a,d]-cyclohepten-5,10-imine | 111305-45-4

• 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: 3-bromo-10,11-dihydro-5-methyl-5H-dibenzo[a,d]-cyclohepten-5,10-imine
• 英文别名: L-639441；3-bromo-10,11-dihydro-5-methyl-5H-dibenzocyclohepten-5,10-imine；3-bromo-10,11-dihydro-5-methyl-5H-dibenzo[a,d]-cyclohepten-5, 10-imine；3-bromo-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine；3-bromo-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine；4-bromo-1-methyl-16-azatetracyclo[7.6.1.02,7.010,15]hexadeca-2(7),3,5,10,12,14-hexaene
• CAS: 111305-45-4
• 化学式: C₁₆H₁₄BrN
• 分子量: 300.198
• InChiKey: JHHJEEKLDDSWTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-bromo-10,11-dihydro-5-methyl-5H-dibenzo[a,d]-cyclohepten-5,10-imine 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 18.0h， 生成 tert-butyl 4-hydroxy-1-methyl-16-azatetracyclo[7.6.1.02,7.010,15]hexadeca-2(7),3,5,10,12,14-hexaene-16-carboxylate
  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
• 作为产物：
  描述：

  3-bromo-5H-dibenzo[a,d]cyclohepten-5-one 在 二氯乙酸 、 硼烷四氢呋喃络合物 、 盐酸羟胺 、 potassium tert-butylate 、 sodium acetate 、 乙酸酐 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 58.25h， 生成 3-bromo-10,11-dihydro-5-methyl-5H-dibenzo[a,d]-cyclohepten-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

• 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。
• Substituted dibenzocycloheptenimines
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US04996211A1

  公开（公告）日：1991-02-26

  The present invention provides a compound of formula (I): ##STR1## or a pharmaceutically acceptable salt thereof, wherein one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 represents a hydrocarbon or hydrocarbyloxycarbonyl group and the remaining groups R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represent hydrogen, hydrocarbon, hydrocarbyloxycarbonyl, halogen, hydroxy or C.sub.1-6 alkoxy, or R.sup.1 and R.sup.2 or R.sup.3 and R.sup.4 may together represent the residue of a carbocyclic ring; R.sup.5 and R.sup.6 independently represent hydrogen, hydrocarbon, hydroxy or fluoro; R.sup.7 represents hydrogen or C.sub.1-3 alkyl; and R.sup.8 represents methyl or ethyl; which compounds are useful as anticonvulsant agents and in the treatment of neurodegenerative diseases.

  本发明提供了式(I)的化合物：##STR1##或其药用可接受的盐，其中R.sup.1、R.sup.2、R.sup.3和R.sup.4中的一个代表烃基或烃基氧羰基基团，其余的基团R.sup.1、R.sup.2、R.sup.3和R.sup.4独立地代表氢、烃基、烃基氧羰基、卤素、羟基或C.sub.1-6烷氧基，或R.sup.1和R.sup.2或R.sup.3和R.sup.4可以一起代表环烷基环的残基；R.sup.5和R.sup.6独立地代表氢、烃基、羟基或氟；R.sup.7代表氢或C.sub.1-3烷基；R.sup.8代表甲基或乙基；这些化合物在抗抽搐剂和神经退行性疾病治疗中有用。
• US4399141A
  申请人：——

  公开号：US4399141A

  公开（公告）日：1983-08-16
• US4996211A
  申请人：——

  公开号：US4996211A

  公开（公告）日：1991-02-26
• 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.