4,5,6,7,8,9,10,11,13,17a,18,19,20,21,22,22a-hexadecahydro-13,23-dimethyl-14,17-etheno-19,22-imino-1H-cyclohept[c][1,9]oxaazacyclononadecine-3,12-dione | 909488-14-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 4,5,6,7,8,9,10,11,13,17a,18,19,20,21,22,22a-hexadecahydro-13,23-dimethyl-14,17-etheno-19,22-imino-1H-cyclohept[c][1,9]oxaazacyclononadecine-3,12-dione
• 英文别名: (2S,4S,7R,8S)-21,27-dimethyl-10-oxa-21,27-diazatetracyclo[20.2.2.14,7.02,8]heptacosa-1(25),22(26),23-triene-11,20-dione
• CAS: 909488-14-8
• 化学式: C₂₆H₃₈N₂O₃
• 分子量: 426.599
• InChiKey: DBPGONCPPLDYIH-UARRHKHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  31
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,5,6,7,8,9,10,11,13,17a,18,19,20,21,22,22a-hexadecahydro-13,23-dimethyl-14,17-etheno-19,22-imino-1H-cyclohept[c][1,9]oxaazacyclononadecine-3,12-dione 在 9-硼双环[3.3.1]壬烷 作用下， 以 四氢呋喃 为溶剂， 以4%的产率得到5,6,7,8,9,10,11,12,14,18a,19,20,21,22,23,23a-hexadecahydro-14,24-dimethyl-15,18-etheno-20,23-iminocyclohept[c][1,9]oxaazacycloeicosine-3(1H,4H)-one
  参考文献：
  名称：

  Synthesis and Monoamine Transporter Binding Properties of 2,3-Cyclo Analogues of 3β-(4‘-Aminophenyl)-2β-tropanemethanol

  摘要：

  A series of cyclo-3 beta-(4-aminophenyl)-2 beta-tropanemethanol analogues (5a-m) possessing varying linker groups between the 2- and 3-position on the tropane ring were synthesized and evaluated for their monoamine transporter binding properties. The results show that binding to the dopamine and serotonin transporters (DAT and 5-HTT) is highly dependent on the specific linker used. Cyclo-3 beta-(4-aminophenyl)-2 beta-tropanemethanol pimelic acid ester/amide (5b) had an IC50 of 3.8 nM at the DAT. Cyclo-3 beta-(4-aminophenyl)2 beta-tropanemethanol sebacic acid ester/amide (5e) had a K-i of 1.9 nM at the 5-HTT and was 68- and 737-fold selective for the 5-HTT relative to the DAT and NET. Small changes to the size as well as the electrostatic and hydrophobic properties of the 2,3-linker in 5b or 5e led to much less potent analogues at all three transporters. These results suggest that the high affinity for 5b and 5e at the DAT and 5-HTT may be due to their specific conformational properties.

  DOI：

  10.1021/jm060287w
• 作为产物：
  描述：

  3β-(4-aminophenyl)-2β-tropane-2β-carboxylic acid methyl ester 在 lithium aluminium tetrahydride 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 4,5,6,7,8,9,10,11,13,17a,18,19,20,21,22,22a-hexadecahydro-13,23-dimethyl-14,17-etheno-19,22-imino-1H-cyclohept[c][1,9]oxaazacyclononadecine-3,12-dione
  参考文献：
  名称：

  Synthesis and Monoamine Transporter Binding Properties of 2,3-Cyclo Analogues of 3β-(4‘-Aminophenyl)-2β-tropanemethanol

  摘要：

  A series of cyclo-3 beta-(4-aminophenyl)-2 beta-tropanemethanol analogues (5a-m) possessing varying linker groups between the 2- and 3-position on the tropane ring were synthesized and evaluated for their monoamine transporter binding properties. The results show that binding to the dopamine and serotonin transporters (DAT and 5-HTT) is highly dependent on the specific linker used. Cyclo-3 beta-(4-aminophenyl)-2 beta-tropanemethanol pimelic acid ester/amide (5b) had an IC50 of 3.8 nM at the DAT. Cyclo-3 beta-(4-aminophenyl)2 beta-tropanemethanol sebacic acid ester/amide (5e) had a K-i of 1.9 nM at the 5-HTT and was 68- and 737-fold selective for the 5-HTT relative to the DAT and NET. Small changes to the size as well as the electrostatic and hydrophobic properties of the 2,3-linker in 5b or 5e led to much less potent analogues at all three transporters. These results suggest that the high affinity for 5b and 5e at the DAT and 5-HTT may be due to their specific conformational properties.

  DOI：

  10.1021/jm060287w

文献信息

• Synthesis and Monoamine Transporter Binding Properties of 2,3-Cyclo Analogues of 3β-(4‘-Aminophenyl)-2β-tropanemethanol
  作者：F. Ivy Carroll、Bruce E. Blough、Xiaodong Huang、Zhe Nie、S. Wayne Mascarella、Jeffrey Deschamps、Hernán A. Navarro

  DOI：10.1021/jm060287w

  日期：2006.7.1

  A series of cyclo-3 beta-(4-aminophenyl)-2 beta-tropanemethanol analogues (5a-m) possessing varying linker groups between the 2- and 3-position on the tropane ring were synthesized and evaluated for their monoamine transporter binding properties. The results show that binding to the dopamine and serotonin transporters (DAT and 5-HTT) is highly dependent on the specific linker used. Cyclo-3 beta-(4-aminophenyl)-2 beta-tropanemethanol pimelic acid ester/amide (5b) had an IC50 of 3.8 nM at the DAT. Cyclo-3 beta-(4-aminophenyl)2 beta-tropanemethanol sebacic acid ester/amide (5e) had a K-i of 1.9 nM at the 5-HTT and was 68- and 737-fold selective for the 5-HTT relative to the DAT and NET. Small changes to the size as well as the electrostatic and hydrophobic properties of the 2,3-linker in 5b or 5e led to much less potent analogues at all three transporters. These results suggest that the high affinity for 5b and 5e at the DAT and 5-HTT may be due to their specific conformational properties.