Trifluoro-methanesulfonic acid 11-oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-8-yl ester | 199605-79-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: Trifluoro-methanesulfonic acid 11-oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-8-yl ester
• 英文别名: (6-Oxo-5,11-dihydrobenzo[b][1,4]benzodiazepin-3-yl) trifluoromethanesulfonate
• CAS: 199605-79-3
• 化学式: C₁₄H₉F₃N₂O₄S
• 分子量: 358.298
• InChiKey: RXPOKXYYBXIIKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Trifluoro-methanesulfonic acid 11-oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-8-yl ester 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 6.0h， 生成 8-(trifluoromethylsulfonyloxy)-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Triflate-Substituted Analogues of Clozapine:  Identification of a Novel Atypical Neuroleptic

  摘要：

  The trifluoromethanesulonyloxy (TfO) analogues 3 and 4 of 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine (clozapine, 1) and its 2-chloro isomer (iso-clozapine, 2), respectively, were synthesized via their OMe and OH analogues with the conventional synthetic method of the tricyclic dibenzodiazepines and evaluated pharmacologically along with their parent drugs. The binding profile of the 2-OTf analogue (4) is comparable to the binding profile of 1, although the affinity for the dopamine (DA) D-2 receptors is higher (IC50 values are 31 nM and 330 nM for compounds 4 and 1, respectively). Interestingly, no notable affinity for muscarinic receptors could be detected in compound 4. On the contrary, the 3-OTf analogue 3 only displayed affinity for muscarinic M-1 receptors (IC50 value 35 nM) and no affinity (IC50 value > 500 nM) for the other receptors tested. The 10 mu mol/kg sc dose, but nod the 10 mu mol/kg po dose, of compound 4 stimulated the output of DA, Increases of 80% and 35% in DOPAC output from the dorsal striatum were seen after sc and po administrations of 10 mu mol/kg of compound 4, respectively. Doses up to 100 mu mol/kg of compound 3 had no effect on either parameter. Doses up to 100 mu mol/kg of compound 4 were not cataleptogenic, but significantly decreased apomorphine-induced locomotor activity. In conclusion, compound 4 (GMC1-169) is a new clozapine-like neuroleptic candidate, which is lacking anticholinergic properties and displays a higher potency, as compared to clozapine (1) itself.

  DOI：

  10.1021/jm9704457
• 作为产物：
  描述：

  8-methoxy-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one 在 三氯化铝 、 三乙胺 、 乙硫醇 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 生成 Trifluoro-methanesulfonic acid 11-oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-8-yl ester
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Triflate-Substituted Analogues of Clozapine:  Identification of a Novel Atypical Neuroleptic

  摘要：

  The trifluoromethanesulonyloxy (TfO) analogues 3 and 4 of 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine (clozapine, 1) and its 2-chloro isomer (iso-clozapine, 2), respectively, were synthesized via their OMe and OH analogues with the conventional synthetic method of the tricyclic dibenzodiazepines and evaluated pharmacologically along with their parent drugs. The binding profile of the 2-OTf analogue (4) is comparable to the binding profile of 1, although the affinity for the dopamine (DA) D-2 receptors is higher (IC50 values are 31 nM and 330 nM for compounds 4 and 1, respectively). Interestingly, no notable affinity for muscarinic receptors could be detected in compound 4. On the contrary, the 3-OTf analogue 3 only displayed affinity for muscarinic M-1 receptors (IC50 value 35 nM) and no affinity (IC50 value > 500 nM) for the other receptors tested. The 10 mu mol/kg sc dose, but nod the 10 mu mol/kg po dose, of compound 4 stimulated the output of DA, Increases of 80% and 35% in DOPAC output from the dorsal striatum were seen after sc and po administrations of 10 mu mol/kg of compound 4, respectively. Doses up to 100 mu mol/kg of compound 3 had no effect on either parameter. Doses up to 100 mu mol/kg of compound 4 were not cataleptogenic, but significantly decreased apomorphine-induced locomotor activity. In conclusion, compound 4 (GMC1-169) is a new clozapine-like neuroleptic candidate, which is lacking anticholinergic properties and displays a higher potency, as compared to clozapine (1) itself.

  DOI：

  10.1021/jm9704457

文献信息

• Synthesis and Pharmacological Evaluation of Triflate-Substituted Analogues of Clozapine:  Identification of a Novel Atypical Neuroleptic
  作者：Yi Liao、Peter DeBoer、Eddie Meier、Håkan Wikström

  DOI：10.1021/jm9704457

  日期：1997.12.1

  The trifluoromethanesulonyloxy (TfO) analogues 3 and 4 of 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine (clozapine, 1) and its 2-chloro isomer (iso-clozapine, 2), respectively, were synthesized via their OMe and OH analogues with the conventional synthetic method of the tricyclic dibenzodiazepines and evaluated pharmacologically along with their parent drugs. The binding profile of the 2-OTf analogue (4) is comparable to the binding profile of 1, although the affinity for the dopamine (DA) D-2 receptors is higher (IC50 values are 31 nM and 330 nM for compounds 4 and 1, respectively). Interestingly, no notable affinity for muscarinic receptors could be detected in compound 4. On the contrary, the 3-OTf analogue 3 only displayed affinity for muscarinic M-1 receptors (IC50 value 35 nM) and no affinity (IC50 value > 500 nM) for the other receptors tested. The 10 mu mol/kg sc dose, but nod the 10 mu mol/kg po dose, of compound 4 stimulated the output of DA, Increases of 80% and 35% in DOPAC output from the dorsal striatum were seen after sc and po administrations of 10 mu mol/kg of compound 4, respectively. Doses up to 100 mu mol/kg of compound 3 had no effect on either parameter. Doses up to 100 mu mol/kg of compound 4 were not cataleptogenic, but significantly decreased apomorphine-induced locomotor activity. In conclusion, compound 4 (GMC1-169) is a new clozapine-like neuroleptic candidate, which is lacking anticholinergic properties and displays a higher potency, as compared to clozapine (1) itself.