(R,S)-(+/-)-3-(4-benzyloxyindol-3-yl)-N-methylsuccinimide | 250672-67-4

• 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: (R,S)-(+/-)-3-(4-benzyloxyindol-3-yl)-N-methylsuccinimide
• 英文别名: 3-(4-(benzyloxy)-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione；1-methyl-3-(4-phenylmethoxy-1H-indol-3-yl)pyrrolidine-2,5-dione
• CAS: 250672-67-4
• 化学式: C₂₀H₁₈N₂O₃
• 分子量: 334.375
• InChiKey: WRIVMJXFPBKCDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  62.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R,S)-(+/-)-3-(4-benzyloxyindol-3-yl)-N-methylsuccinimide 在 palladium on activated charcoal lithium aluminium tetrahydride 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 10.0h， 生成 3-(1-Methyl-pyrrolidin-3-yl)-1H-indol-4-ol
  参考文献：
  名称：

  Further Studies on Oxygenated Tryptamines with LSD-like Activity Incorporating a Chiral Pyrrolidine Moiety into the Side Chain

  摘要：

  The enantiomers of 3-(N-methylpyrrolidin-2-ylmethyl)-5-methoxyindole, 1, and 3-(N-methylpyrrolidin-2-ylmethyl)-4-hydoxyindole, 3, were prepared using an asymmetric synthesis that employed (+)- or (-)-proline. A new approach was developed that had certain advantages over the synthesis originally reported for the isomers of 1. (+)-3-(N-Methylpyrrolidin-3-yl)-4-hydroxyindole, 5, was also prepared as a rigid analogue of psilocin and compared with its 5-methoxy counterpart 4. Radioligand competition assays were used to assess the affinity of compounds for the 5-HT2A receptor labeled with the agonist ligand [I-125]DOI and the antagonist ligand [H-3]MDL100907. Two-lever drug discrimination assays in rats trained to discriminate either LSD or DOI from saline were employed to assess the hallucinogen-like behavioral properties of these rigid tryptamine analogues. The receptor binding assay results clearly demonstrated a stereochemical preference for the R enantiomers that did not discriminate the position of the oxygen function. The receptor is 10-20-fold more selective for the R isomers. The affinities of the R enantiomers were virtually identical for both 1 and 3 at the agonist-labeled receptor, while racemic 4 and 5 had about one-tenth the affinity. The drug discrimination data in both LSD- and DOI-trained rats paralleled the binding data using [I-125]DOI displacement. Both (R)-1 and (R)-3 are about equipotent, comparable to DOI in activity but about 10-fold less potent than LSD. Compound 4 produced only partial substitution, even at a dose nearly 5-fold higher than for (R)-1. Based on conformational energies, it seems doubtful that these compounds bind to the 5-HT2A receptor in an ergoline-like conformation. The results also suggest that both 1 and 3 would possess LSD-like psychopharmacology in humans.

  DOI：

  10.1021/jm990325u
• 作为产物：
  描述：

  N-甲基马来酰亚胺 、 4-苄氧基吲哚 在 溶剂黄146 作用下， 反应 96.0h， 以40.4%的产率得到(R,S)-(+/-)-3-(4-benzyloxyindol-3-yl)-N-methylsuccinimide
  参考文献：
  名称：

  [EN] 3-CYCLIC AMINE-INDOLE DERIVATIVES AS SEROTONERGIC AGENTS FOR THE TREATMENT OF CNS DISORDERS
  [FR] DÉRIVÉS D'AMINE-INDOLE 3-CYCLIQUE UTILISÉS EN TANT QU'AGENTS SÉROTONERGIQUES POUR LE TRAITEMENT DE TROUBLES DU SYSTÈME NERVEUX CENTRAL

  摘要：

  本申请涉及一般式(I)的3-环氨基吲哚衍生物，其制备过程，包含它们的组合物以及它们在细胞中激活5-羟色胺受体和治疗可通过细胞中5-羟色胺受体激活治疗的疾病、失调或病症的用途。这些疾病、失调或病症包括精神病和精神疾病。(式(I))

  公开号：

  WO2022120475A1

文献信息

• [EN] 3-CYCLIC AMINE-INDOLE DERIVATIVES AS SEROTONERGIC AGENTS FOR THE TREATMENT OF CNS DISORDERS<br/>[FR] DÉRIVÉS D'AMINE-INDOLE 3-CYCLIQUE UTILISÉS EN TANT QU'AGENTS SÉROTONERGIQUES POUR LE TRAITEMENT DE TROUBLES DU SYSTÈME NERVEUX CENTRAL
  申请人：MINDSET PHARMA INC

  公开号：WO2022120475A1

  公开（公告）日：2022-06-16

  The present application relates to 3-cyclic amine-indole derivatives of general Formula (I), to processes for their preparation, to compositions comprising them and to their use in activation of a serotonin receptor in a cell, and treating diseases, disorders or conditions treatable by activation of a serotonin receptor in a cell. The diseases, disorders or conditions include, for example, psychosis and mental illness. (Formula (I))

  本申请涉及一般式(I)的3-环氨基吲哚衍生物，其制备过程，包含它们的组合物以及它们在细胞中激活5-羟色胺受体和治疗可通过细胞中5-羟色胺受体激活治疗的疾病、失调或病症的用途。这些疾病、失调或病症包括精神病和精神疾病。(式(I))
• Further Studies on Oxygenated Tryptamines with LSD-like Activity Incorporating a Chiral Pyrrolidine Moiety into the Side Chain
  作者：Madina Gerasimov、Danuta Marona-Lewicka、Deborah M. Kurrasch-Orbaugh、Amjad M. Qandil、David E. Nichols

  DOI：10.1021/jm990325u

  日期：1999.10.1

  The enantiomers of 3-(N-methylpyrrolidin-2-ylmethyl)-5-methoxyindole, 1, and 3-(N-methylpyrrolidin-2-ylmethyl)-4-hydoxyindole, 3, were prepared using an asymmetric synthesis that employed (+)- or (-)-proline. A new approach was developed that had certain advantages over the synthesis originally reported for the isomers of 1. (+)-3-(N-Methylpyrrolidin-3-yl)-4-hydroxyindole, 5, was also prepared as a rigid analogue of psilocin and compared with its 5-methoxy counterpart 4. Radioligand competition assays were used to assess the affinity of compounds for the 5-HT2A receptor labeled with the agonist ligand [I-125]DOI and the antagonist ligand [H-3]MDL100907. Two-lever drug discrimination assays in rats trained to discriminate either LSD or DOI from saline were employed to assess the hallucinogen-like behavioral properties of these rigid tryptamine analogues. The receptor binding assay results clearly demonstrated a stereochemical preference for the R enantiomers that did not discriminate the position of the oxygen function. The receptor is 10-20-fold more selective for the R isomers. The affinities of the R enantiomers were virtually identical for both 1 and 3 at the agonist-labeled receptor, while racemic 4 and 5 had about one-tenth the affinity. The drug discrimination data in both LSD- and DOI-trained rats paralleled the binding data using [I-125]DOI displacement. Both (R)-1 and (R)-3 are about equipotent, comparable to DOI in activity but about 10-fold less potent than LSD. Compound 4 produced only partial substitution, even at a dose nearly 5-fold higher than for (R)-1. Based on conformational energies, it seems doubtful that these compounds bind to the 5-HT2A receptor in an ergoline-like conformation. The results also suggest that both 1 and 3 would possess LSD-like psychopharmacology in humans.