L-639057 | 87747-33-9

• 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: L-639057
• 英文别名: 1-Ethyl-16-azatetracyclo[7.6.1.02,7.010,15]hexadeca-2,4,6,10,12,14-hexaene
• CAS: 87747-33-9
• 化学式: C₁₇H₁₇N
• 分子量: 235.329
• InChiKey: PWOMGUJYIACTOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 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：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  (+/-)-N-<(tert-butylimino)methyl>-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine 在 六甲基磷酰三胺 、 氢氧化钾 、 仲丁基锂 作用下， 以 乙二醇 为溶剂， 反应 0.75h， 生成 L-639057
  参考文献：
  名称：

  Synthesis and structure-activity relationship of C5-substituted analogs of (.+-.)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine [(.+-.)-desmethyl-MK801]: ligands for the NMDA receptor-coupled phencyclidine binding site

  摘要：

  A series of eight C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (+-)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaboration of the C5-ethyl ester derivative. Analogues possessing large (e.g. propyl and larger) lipophilic substituents displace [3H]-1-(1-thienylcyclohexyl)piperidine [( 3H]TCP) from the high-affinity phencyclidine (PCP) binding site in rat brain homogenates only at high concentrations (Ki greater than 1000 nM); however, the presence of a polar amino functionality (e.g. 2-aminoethyl) offsets this effect (Ki = 20 nM). Thus, the boundary condition for lipophilic substituents larger than ethyl appears to be polar in nature. Interaction of the 11 relatively small (MR less than 14) C5-substituted analogues of 1 with the high-affinity PCP binding site associated with the N-methyl-D-aspartate (NMDA) receptor is best described by the equation log (1/Ki) = -5.83F + 0.64 pi + 7.41 (r = 0.90).

  DOI：

  10.1021/jm00165a029

文献信息

• CHRISTY M. E.; ANDERSON P. S.; BRITCHER S. F.; COLTON C. D.; EVANS B. E.;+, J. ORG. CHEM., 1979, 44, NO 18, 3117-3127
  作者：CHRISTY M. E.、 ANDERSON P. S.、 BRITCHER S. F.、 COLTON C. D.、 EVANS B. E.、+

  DOI：——

  日期：——
• US4399141A
  申请人：——

  公开号：US4399141A

  公开（公告）日：1983-08-16
• Synthesis and structure-activity relationship of C5-substituted analogs of (.+-.)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine [(.+-.)-desmethyl-MK801]: ligands for the NMDA receptor-coupled phencyclidine binding site
  作者：James A. Monn、Andrew Thurkauf、Mariena V. Mattson、Arthur E. Jacobson、Kenner C. Rice

  DOI：10.1021/jm00165a029

  日期：1990.3

  A series of eight C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (+-)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaboration of the C5-ethyl ester derivative. Analogues possessing large (e.g. propyl and larger) lipophilic substituents displace [3H]-1-(1-thienylcyclohexyl)piperidine [( 3H]TCP) from the high-affinity phencyclidine (PCP) binding site in rat brain homogenates only at high concentrations (Ki greater than 1000 nM); however, the presence of a polar amino functionality (e.g. 2-aminoethyl) offsets this effect (Ki = 20 nM). Thus, the boundary condition for lipophilic substituents larger than ethyl appears to be polar in nature. Interaction of the 11 relatively small (MR less than 14) C5-substituted analogues of 1 with the high-affinity PCP binding site associated with the N-methyl-D-aspartate (NMDA) receptor is best described by the equation log (1/Ki) = -5.83F + 0.64 pi + 7.41 (r = 0.90).