2-(4-Nitrophenethyl)-2,3,5,6,10,10a-hexahydro-1H,4H-acenaphtho[1,8a-c]pyrrole-1,3,4-trione | 252960-96-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-(4-Nitrophenethyl)-2,3,5,6,10,10a-hexahydro-1H,4H-acenaphtho[1,8a-c]pyrrole-1,3,4-trione
• 英文别名: 13-[2-(4-Nitrophenyl)ethyl]-13-azatetracyclo[7.5.1.01,11.05,15]pentadeca-5(15),6,8-triene-10,12,14-trione
• CAS: 252960-96-6
• 化学式: C₂₂H₁₈N₂O₅
• 分子量: 390.395
• InChiKey: PJEZPBWFHSYCPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  100
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-Nitrophenethyl)-2,3,5,6,10,10a-hexahydro-1H,4H-acenaphtho[1,8a-c]pyrrole-1,3,4-trione 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium nitrite 作用下， 以 乙醇 为溶剂， 反应 27.5h， 生成 Ethyl 5-[2-(1,3,4-trioxo-2,3,5,6,10,10a-hexahydro-1H,4H-acenaphtho[1,8a-c]pyrrolyl)ethyl]-3-[2-(dimethylamino)ethyl]-1H-indole-2-carboxylate
  参考文献：
  名称：

  Synthesis and serotonergic activity of a series of 2-(N-benzyl)carboxamido-5-substituted-N,N-dimethyltryptamine derivatives: novel antagonists for the vascular 5-HT1B-like receptors

  摘要：

  0)。

  DOI：

  10.1039/a903141c
• 作为产物：
  描述：

  3a,4,5,6-四氢琥珀酰亚胺并(3,4-b)-苊-10-酮 、 对硝基苯乙醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以78%的产率得到2-(4-Nitrophenethyl)-2,3,5,6,10,10a-hexahydro-1H,4H-acenaphtho[1,8a-c]pyrrole-1,3,4-trione
  参考文献：
  名称：

  Synthesis and serotonergic activity of a series of 2-(N-benzyl)carboxamido-5-substituted-N,N-dimethyltryptamine derivatives: novel antagonists for the vascular 5-HT1B-like receptors

  摘要：

  0)。

  DOI：

  10.1039/a903141c

文献信息

• Synthesis and serotonergic activity of a series of 2-(N-benzyl)carboxamido-5-substituted-N,N-dimethyltryptamine derivatives: novel antagonists for the vascular 5-HT1B-like receptors
  作者：Gerard P. Moloney、Graeme R. Martin、Neil Mathews、Heather Hobbs、Susan Dodsworth、Pang Yih Sang、Cameron Knight、Miles Maxwell、Robert C. Glen

  DOI：10.1039/a903141c

  日期：——

  The synthesis and vascular 5-HT1B-like receptor activity of a novel series of 2-(N-benzyl)carboxamido-5-substituted-N,N-dimethyltryptamine derivatives is described. Modifications to the 5-ethylene linked heterocycle are explored. Compounds such as N-benzyl-5-[2-(phthalimido)ethyl]-3-[2-(dimethylamino)ethyl]-1H-indole-2-carboxamide 22 (pKB = 7.33), the 2-aminobenzyl analogue 24 (pKB = 7.19), which both contain a phthalimide group, and N-benzyl-5-[2-(1-benzyl-2,5-dioxoimidazolidin-4-yl)ethyl]-3-[2-(dimethylamino)ethyl]-1H-indole-2-carboxamide 81 (pKB = 7.05), which incorporates an N-benzylhydantoin moiety, have good 5-HT1B-like affinity and indicate that there may be a hydrophobic binding pocket within the vascular 5-HT1B-like receptor previously not considered. Compounds including N-benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(2,4-dioxo-1,3-thiazolidinyl)ethyl]-1H-indole-2-carboxamide 39 (pKB = 7.35) and the dimethyl analogue 46 (pKB = 7.48) which contain a 2,4-thiazolidinedione moiety have good vascular 5-HT1B-like receptor affinity and show that the sulfur atom is well tolerated. Compound 61 which includes a methylsulfonyl substituent on the 1-nitrogen of the hydantoin ring system has the highest recorded 5-HT1B-like affinity for this series (pKB = 7.54) and it is proposed that this functional group can interact with a secondary hydrogen bonding region within the receptor. Compounds 22, 24, 39, 46, 61 and 81 also exhibited good selectivity over the α1-adrenoceptors. The most selective compound from this series is 46 which contains a 5,5-dimethylthiazolidine-2,4-dione group and which is 66-fold selective over the α1-adrenoceptors. This finding is consistent with the previous discovery that 5,5-dimethyl substitution on the hydantoin group in a related series of compounds afforded superior selectivity for 5-HT1B-like receptors over α1-adrenoceptors and other 5-HT receptors, in particular 5-HT2A receptors, relative to unsubstituted hydantoin analogues. The selectivity of these compounds for the vascular 5-HT1B-like receptor is discussed. Structure–activity relationship indicated a significant steric requirement of the 5-HT1B-like receptor subtype. Potential modes of binding for several of the compounds to a vascular 5-HT1B-like receptor pharmacophore model are also proposed.

  0)。