N-Benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(2,4-dioxo-1,3-thiazolidin-3-yl)ethyl]-1H-indole-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-Benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(2,4-dioxo-1,3-thiazolidin-3-yl)ethyl]-1H-indole-2-carboxamide
• 化学式: C₂₅H₂₈N₄O₃S
• 分子量: 464.588
• InChiKey: BQJGRQWALNIBKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 3-(2-aminoethyl)-N-benzyl-5-[2-(2,4-dioxo-1,3-thiazolidin-3-yl)ethyl]-1H-indole-2-carboxamide 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 以10%的产率得到N-Benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(2,4-dioxo-1,3-thiazolidin-3-yl)ethyl]-1H-indole-2-carboxamide
  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)。