(+)-3-nitro-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine

• 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-nitro-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine
• 英文别名: (+)-3-nitro-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine；(1S,9R)-1-methyl-4-nitro-16-azatetracyclo[7.6.1.02,7.010,15]hexadeca-2(7),3,5,10,12,14-hexaene
• 化学式: C₁₆H₁₄N₂O₂
• 分子量: 266.299
• InChiKey: RKKXEXALLJUWEY-HZPDHXFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 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：
  57.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+)-3-nitro-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine 在 palladium on activated charcoal 氢气 、 碳酸氢钠 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、206.84 kPa 条件下， 反应 55.0h， 生成 (+)-N-<(tert-butyloxy)carbonyl>-3-amino-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine
  参考文献：
  名称：

  Synthesis and binding properties of MK-801 isothiocyanates; (+)-3-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrochloride: a new, potent and selective electrophilic affinity ligand for the NMDA receptor-coupled phencyclidine binding site

  摘要：

  Three new site-directed irreversible (wash-resistant) ligands for the high-affinity phencyclidine (PCP) binding site associated with the N-methyl-D-aspartate (NMDA) receptor were synthesized and their binding characteristics were studied. (+)-3- And (+)-2-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrochloride ((+)-8a,b.HCl) were prepared in four steps from the corresponding nitro derivatives (+)-4a,b, which were obtained by nitration of (+)-3 (MK-801). In the same way the optical antipode (-)-8a.HCl was synthesized from (-)-3. At a concentration of 100 nM, the 3-isothiocyanate derivative (+)-8a irreversibly labeled approximately 50% of the (+)-[H-3]-3 binding sites, compared to 20 muM needed for its optical antipode (-)-8a and the 2-isothiocyanate(+)-8b. The apparent K(i) values for reversible inhibition of (+)-[H-3]-3 binding by (+)- and (-)-8a and (+)-8b were 37, 838, and 843 nM, respectively. In contrast, metaphit (1b) and etoxadrol m-isothiocyanate (2b), two previously reported irreversible ligands for the PCP binding site, label about 50% of the (+)-[H-3]-3 binding sites at 100 muM and 250 nM, respectively, with apparent K(i) values for reversible inhibition of 535 and 94 nM. Compound (+)-8a is also a selective affinity ligand, displaying little or no irreversible in vitro affinity at 100 muM for opioid, benzodiazepine, muscarinic, and dopamine receptors. At a 25 muM concentration, (+)-8a caused an irreversible 52% reduction of binding to sigma1-receptors. Compound (+)-8a is the most potent known electrophilic affinity label for the PCP binding site. Its potency and selectivity should enable it to be a valuable tool for the elucidation of the structure and function of the NMDA receptor-associated PCP binding site in the mammalian central nervous system.

  DOI：

  10.1021/jm00069a008
• 作为产物：
  描述：

  地佐环平 在 硫酸 、 硝酸 、 溶剂黄146 作用下， 反应 104.0h， 以80%的产率得到(+)-3-nitro-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine
  参考文献：
  名称：

  Synthesis and binding properties of MK-801 isothiocyanates; (+)-3-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrochloride: a new, potent and selective electrophilic affinity ligand for the NMDA receptor-coupled phencyclidine binding site

  摘要：

  Three new site-directed irreversible (wash-resistant) ligands for the high-affinity phencyclidine (PCP) binding site associated with the N-methyl-D-aspartate (NMDA) receptor were synthesized and their binding characteristics were studied. (+)-3- And (+)-2-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrochloride ((+)-8a,b.HCl) were prepared in four steps from the corresponding nitro derivatives (+)-4a,b, which were obtained by nitration of (+)-3 (MK-801). In the same way the optical antipode (-)-8a.HCl was synthesized from (-)-3. At a concentration of 100 nM, the 3-isothiocyanate derivative (+)-8a irreversibly labeled approximately 50% of the (+)-[H-3]-3 binding sites, compared to 20 muM needed for its optical antipode (-)-8a and the 2-isothiocyanate(+)-8b. The apparent K(i) values for reversible inhibition of (+)-[H-3]-3 binding by (+)- and (-)-8a and (+)-8b were 37, 838, and 843 nM, respectively. In contrast, metaphit (1b) and etoxadrol m-isothiocyanate (2b), two previously reported irreversible ligands for the PCP binding site, label about 50% of the (+)-[H-3]-3 binding sites at 100 muM and 250 nM, respectively, with apparent K(i) values for reversible inhibition of 535 and 94 nM. Compound (+)-8a is also a selective affinity ligand, displaying little or no irreversible in vitro affinity at 100 muM for opioid, benzodiazepine, muscarinic, and dopamine receptors. At a 25 muM concentration, (+)-8a caused an irreversible 52% reduction of binding to sigma1-receptors. Compound (+)-8a is the most potent known electrophilic affinity label for the PCP binding site. Its potency and selectivity should enable it to be a valuable tool for the elucidation of the structure and function of the NMDA receptor-associated PCP binding site in the mammalian central nervous system.

  DOI：

  10.1021/jm00069a008

文献信息

• Synthesis and binding properties of MK-801 isothiocyanates; (+)-3-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrochloride: a new, potent and selective electrophilic affinity ligand for the NMDA receptor-coupled phencyclidine binding site
  作者：Joannes T. M. Linders、James A. Monn、Mariena V. Mattson、Clifford George、Arthur E. Jacobson、Kenner C. Rice

  DOI：10.1021/jm00069a008

  日期：1993.8

  Three new site-directed irreversible (wash-resistant) ligands for the high-affinity phencyclidine (PCP) binding site associated with the N-methyl-D-aspartate (NMDA) receptor were synthesized and their binding characteristics were studied. (+)-3- And (+)-2-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrochloride ((+)-8a,b.HCl) were prepared in four steps from the corresponding nitro derivatives (+)-4a,b, which were obtained by nitration of (+)-3 (MK-801). In the same way the optical antipode (-)-8a.HCl was synthesized from (-)-3. At a concentration of 100 nM, the 3-isothiocyanate derivative (+)-8a irreversibly labeled approximately 50% of the (+)-[H-3]-3 binding sites, compared to 20 muM needed for its optical antipode (-)-8a and the 2-isothiocyanate(+)-8b. The apparent K(i) values for reversible inhibition of (+)-[H-3]-3 binding by (+)- and (-)-8a and (+)-8b were 37, 838, and 843 nM, respectively. In contrast, metaphit (1b) and etoxadrol m-isothiocyanate (2b), two previously reported irreversible ligands for the PCP binding site, label about 50% of the (+)-[H-3]-3 binding sites at 100 muM and 250 nM, respectively, with apparent K(i) values for reversible inhibition of 535 and 94 nM. Compound (+)-8a is also a selective affinity ligand, displaying little or no irreversible in vitro affinity at 100 muM for opioid, benzodiazepine, muscarinic, and dopamine receptors. At a 25 muM concentration, (+)-8a caused an irreversible 52% reduction of binding to sigma1-receptors. Compound (+)-8a is the most potent known electrophilic affinity label for the PCP binding site. Its potency and selectivity should enable it to be a valuable tool for the elucidation of the structure and function of the NMDA receptor-associated PCP binding site in the mammalian central nervous system.