(R)-(+)-3-(N-methylpyrrolidin-2-ylmethyl)-4-hydroxyindole | 250672-65-2

• 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)-(+)-3-(N-methylpyrrolidin-2-ylmethyl)-4-hydroxyindole
• 英文别名: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-ol；3-[[(2R)-1-methylpyrrolidin-2-yl]methyl]-1H-indol-4-ol
• CAS: 250672-65-2
• 化学式: C₁₄H₁₈N₂O
• 分子量: 230.31
• InChiKey: XYRKPZYRLSWABB-LLVKDONJSA-N

物化性质

• 熔点：
  135 °C
• 沸点：
  422.5±25.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  39.3
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  戊二酰基二氯 、 (R)-(+)-3-(N-methylpyrrolidin-2-ylmethyl)-4-hydroxyindole 在 三乙胺 、 盐酸 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 生成 bis(3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl) glutarate dihydrochloride
  参考文献：
  名称：

  WO2024026574A1

  摘要：

  公开号：
• 作为产物：
  描述：

  (R)-(+)-3-(N-methylpyrrolidin-2-ylcarbonyl)-4-benzyloxyindole 在 lithium aluminium tetrahydride 作用下， 以 1,4-二氧六环 为溶剂， 生成 (R)-(+)-3-(N-methylpyrrolidin-2-ylmethyl)-4-hydroxyindole
  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

文献信息

• [EN] 3-PYRROLIDINE-INDOLE DERIVATIVES AS SEROTONERGIC PSYCHEDELIC AGENTS FOR THE TREATMENT OF CNS DISORDERS<br/>[FR] DÉRIVÉS DE 3-PYRROLIDINE-INDOLE EN TANT QU'AGENTS PSYCHÉDÉLIQUES SÉROTONINERGIQUES POUR LE TRAITEMENT DE TROUBLES DU SNC
  申请人：MINDSET PHARMA INC

  公开号：WO2021155467A1

  公开（公告）日：2021-08-12

  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, as well as to treating diseases, disorders or conditions by activation of a serotonin receptor in a cell. The diseases, disorders or conditions include, for example, psychosis, mental illnesses, and other neurological diseases, disorders and conditions. Formula (I)

  本申请涉及一般式（I）的3-环氨基吲哚衍生物，以及它们的制备方法、包含它们的组合物和它们在细胞中激活5-羟色胺受体以及通过激活细胞中的5-羟色胺受体治疗疾病、障碍或病况的用途。这些疾病、障碍或病况包括精神病、精神疾病和其他神经疾病、障碍和病况。式（I）：
• 3-PYRROLIDINE-INDOLE DERIVATIVES AS SEROTONERGIC PSYCHEDELIC AGENTS FOR THE TREATMENT OF CNS DISORDERS
  申请人：Mindset Pharma Inc.

  公开号：EP4100403A1

  公开（公告）日：2022-12-14