1-[1-(2,2,2-Trifluoro-acetyl)-2,3-dihydro-1H-indol-6-yloxy]-propan-2-one | 173669-30-2

• 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: 1-[1-(2,2,2-Trifluoro-acetyl)-2,3-dihydro-1H-indol-6-yloxy]-propan-2-one
• 英文别名: 1-[[1-(2,2,2-Trifluoroacetyl)-2,3-dihydroindol-6-yl]oxy]propan-2-one
• CAS: 173669-30-2
• 化学式: C₁₃H₁₂F₃NO₃
• 分子量: 287.238
• InChiKey: SUNCGYNYBSXJGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[1-(2,2,2-Trifluoro-acetyl)-2,3-dihydro-1H-indol-6-yloxy]-propan-2-one 在 sodium hydroxide 、 硫酸 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 3-Methyl-6,7-dihydro-5H-furo[3,2-f]indole
  参考文献：
  名称：

  Synthesis, Biological Activity, and Molecular Modeling Studies of Selective 5-HT_2C/2B Receptor Antagonists

  摘要：

  The synthesis and biological activity are reported for a series of analogues of the previously published indole urea 2 (SB-206553), designed to probe the 5-HT2C receptor binding site. Small molecule modeling studies have been used to define a region in space which is allowed at the 5-HT2C receptor but disallowed at the 5-HT2A receptor. In a complementary approach, docking of 2 into our model of the 5-HT2C receptor has allowed us to propose a novel primary binding interaction for this series of diaryl ureas, involving a potential double hydrogen-bonding interaction between the urea carbonyl oxygen of the ligand and two serine residues in the receptor. The difference of two valine residues in the 5-HT2C receptor for leucine residues in the 5-HT2A receptor is believed to account for the observed 5-HT2C/5-HT2A selectivity with 2.

  DOI：

  10.1021/jm960571v
• 作为产物：
  描述：

  6-硝基吲哚啉 在 palladium on activated charcoal 硫酸 、 氢气 、 potassium carbonate 、 copper(II) sulfate 、 三乙胺 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 68.92h， 生成 1-[1-(2,2,2-Trifluoro-acetyl)-2,3-dihydro-1H-indol-6-yloxy]-propan-2-one
  参考文献：
  名称：

  Synthesis, Biological Activity, and Molecular Modeling Studies of Selective 5-HT_2C/2B Receptor Antagonists

  摘要：

  The synthesis and biological activity are reported for a series of analogues of the previously published indole urea 2 (SB-206553), designed to probe the 5-HT2C receptor binding site. Small molecule modeling studies have been used to define a region in space which is allowed at the 5-HT2C receptor but disallowed at the 5-HT2A receptor. In a complementary approach, docking of 2 into our model of the 5-HT2C receptor has allowed us to propose a novel primary binding interaction for this series of diaryl ureas, involving a potential double hydrogen-bonding interaction between the urea carbonyl oxygen of the ligand and two serine residues in the receptor. The difference of two valine residues in the 5-HT2C receptor for leucine residues in the 5-HT2A receptor is believed to account for the observed 5-HT2C/5-HT2A selectivity with 2.

  DOI：

  10.1021/jm960571v

文献信息

• TRICYCLIC DERIVATIVES AS 5HT 2C? AND 5HT 2B? ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0757687A1

  公开（公告）日：1997-02-12
• [EN] TRICYCLIC DERIVATIVES AS 5HT2C AND 5HT2B ANTAGONISTS<br/>[FR] DERIVES TRICYCLIQUES ANTAGONISTES DE 5HT2C ET DE 5HT2B
  申请人：SMITHKLINE BEECHAM P.L.C.

  公开号：WO1995029177A1

  公开（公告）日：1995-11-02

  (EN) Compounds of formula (I), processes for their preparation and their use as CNS agents are disclosed. In said formula P represents phenyl, a quinoline or isoquinoline residue, or a 5- or 6-membered aromatic heterocyclic ring containing up to three heteroatoms selected from nitrogen, oxygen or sulphur; J represents a bicyclic aromatic or partially saturated ring system; R1 and R2 are independently hydrogen, halogen, hydroxy, oxygen or C1-6alkyl optionally substituted by one or more halogen atoms; R4 is hydrogen, C1-6alkyl, C1-6alkylthio, halogen, nitro, cyano, CF3, NR8R9, CO2R12, CONR12 or OR12, where R8, R9 and R12 are independently hydrogen, C1-6alkyl or arylC1-6alkyl; R5 is hydrogen or C1-6alkyl; n is 2 or 3; and the groups R13 and R14 are independently hydrogen or C1-6alkyl, provided that: P is not a heterocyclic group when J forms a benzothiophene ring.(FR) Composés de la formule (I), leurs procédés de préparation et leur utilisation en tant qu'agents du système nerveux central. Dans cette formule, P représente phényle, un reste de quinoline ou d'isoquinoline, ou un cycle hétérocyclique aromatique à 5 ou 6 chaînons contenant jusqu'à trois hétéroatomes choisis parmi azote, oxygène ou soufre; J représente un système de cycles bicycliques aromatiques ou partiellement saturés; R1 et R2 représentent indépendamment hydrogène, halogène, hydroxy, oxygène ou alcoyle C1-6 éventuellement substitué par un ou plusieurs atomes d'halogène; R4 représente hydrogène, alcoyle C1-6, alcoylthio C1-6, halogène, nitro, cyano, CF3, NR8R9, CO2R12, CONR12 ou OR12, dans lesquels R8, R9 et R12 représentent indépendamment hydrogène, alcoyle C1-6, ou arylalcoyle C1-6; R5 représente hydrogène ou alcoyle C1-6; n vaut 2 ou 3; et les groupes R13 et R14 représentent indépendamment hydrogène ou alcoyle C1-6, à condition que P ne soit pas un groupe hétérocyclique lorsque J forme un cycle benzothiophène.
• Synthesis, Biological Activity, and Molecular Modeling Studies of Selective 5-HT_2C/2B Receptor Antagonists
  作者：Ian T. Forbes、Steven Dabbs、D. Malcolm Duckworth、Peter Ham、Graham E. Jones、Frank D. King、Damian V. Saunders、Frank E. Blaney、Christopher B. Naylor、Gordon S. Baxter、Thomas P. Blackburn、Guy A. Kennett、Martyn D. Wood

  DOI：10.1021/jm960571v

  日期：1996.1.1

  The synthesis and biological activity are reported for a series of analogues of the previously published indole urea 2 (SB-206553), designed to probe the 5-HT2C receptor binding site. Small molecule modeling studies have been used to define a region in space which is allowed at the 5-HT2C receptor but disallowed at the 5-HT2A receptor. In a complementary approach, docking of 2 into our model of the 5-HT2C receptor has allowed us to propose a novel primary binding interaction for this series of diaryl ureas, involving a potential double hydrogen-bonding interaction between the urea carbonyl oxygen of the ligand and two serine residues in the receptor. The difference of two valine residues in the 5-HT2C receptor for leucine residues in the 5-HT2A receptor is believed to account for the observed 5-HT2C/5-HT2A selectivity with 2.