(E)-(2,3-dihydro-6-methoxy-2-phenyl-1H-inden-1-ylidene)acetonitrile | 178677-22-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (E)-(2,3-dihydro-6-methoxy-2-phenyl-1H-inden-1-ylidene)acetonitrile
• 英文别名: (E)-(6-Methoxy-2-phenylindan-1-ylidene)acetonitrile；(2E)-2-(6-methoxy-2-phenyl-2,3-dihydroinden-1-ylidene)acetonitrile
• CAS: 178677-22-0
• 化学式: C₁₈H₁₅NO
• 分子量: 261.323
• InChiKey: ZGSJWIHMXUNYQS-CXUHLZMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-(2,3-dihydro-6-methoxy-2-phenyl-1H-inden-1-ylidene)acetonitrile 在 钴 氨 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 40.0 ℃ 、400.0 kPa 条件下， 生成 2,2,2-trifluoro-N-[2-(5-methoxy-2-phenyl-1H-inden-3-yl)ethyl]acetamide
  参考文献：
  名称：

  Synthesis of a Novel Series of Benzocycloalkene Derivatives as Melatonin Receptor Agonists

  摘要：

  We synthesized a novel series of benzocycloalkene derivatives and evaluated their binding affinities to melatonin receptors. To control the spatial position of the amide group, one of the important pharmacophores, we incorporated an endo double bond, an exo double bond (E- and Z-configurations), and a chiral center (R- and S-configurations) at position 1. The indan derivatives with the S-configuration at position 1 were the most promising in terms of potency and selectivity for the human melatonin receptor (MT, site), while compounds with the R-configuration showed little potential. Our next attempt was to investigate the most favorable conformation of the methoxy group, the other important pharmacophore for binding to the MT, receptor. The introduction of a methyl group at position 5 of the indene ring conserved affinity; however, at position 7, it caused a decrease in affinity. These results suggested that the substitution at position 7 forced the methoxy group to adopt an unfavorable orientation. The optimization of the condensed ring size and substituents led to (S)-8d [(S)-N-[2-(2,3-dihydro-6-methoxy-1H-inden-1-yl)ethyl]propionamide], which had high affinity for the human MT3 receptor (K-i = 0.041 nM) but no significant affinity for the hamster MT3 receptor (K-i = 3570 nM). In addition, a practical synthetic method of chiral N-[2-(2,3-dihydro-1H-inden-1-yl)ethyl]-alkanamides employing asymmetric hydrogenation with (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl-Ru has been established.

  DOI：

  10.1021/jm020114g
• 作为产物：
  描述：

  2,3-dihydro-6-methoxy-2-phenyl-1H-inden-1-one 、 乙腈 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.33h， 以16%的产率得到(E)-(2,3-dihydro-6-methoxy-2-phenyl-1H-inden-1-ylidene)acetonitrile
  参考文献：
  名称：

  Synthesis of a Novel Series of Benzocycloalkene Derivatives as Melatonin Receptor Agonists

  摘要：

  We synthesized a novel series of benzocycloalkene derivatives and evaluated their binding affinities to melatonin receptors. To control the spatial position of the amide group, one of the important pharmacophores, we incorporated an endo double bond, an exo double bond (E- and Z-configurations), and a chiral center (R- and S-configurations) at position 1. The indan derivatives with the S-configuration at position 1 were the most promising in terms of potency and selectivity for the human melatonin receptor (MT, site), while compounds with the R-configuration showed little potential. Our next attempt was to investigate the most favorable conformation of the methoxy group, the other important pharmacophore for binding to the MT, receptor. The introduction of a methyl group at position 5 of the indene ring conserved affinity; however, at position 7, it caused a decrease in affinity. These results suggested that the substitution at position 7 forced the methoxy group to adopt an unfavorable orientation. The optimization of the condensed ring size and substituents led to (S)-8d [(S)-N-[2-(2,3-dihydro-6-methoxy-1H-inden-1-yl)ethyl]propionamide], which had high affinity for the human MT3 receptor (K-i = 0.041 nM) but no significant affinity for the hamster MT3 receptor (K-i = 3570 nM). In addition, a practical synthetic method of chiral N-[2-(2,3-dihydro-1H-inden-1-yl)ethyl]-alkanamides employing asymmetric hydrogenation with (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl-Ru has been established.

  DOI：

  10.1021/jm020114g

文献信息

• Benzocycloalkene compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05922771A1

  公开（公告）日：1999-07-13

  A compound of the formula ##STR1## wherein R.sup.1 and R.sup.2 independently represent H or an optionally substituted hydrocarbon group; R.sup.3 represents an optionally substituted hydrocarbon group; R.sup.4 represents H or a hydrocarbon group; ring A represents a substituted benzene ring; X represents a C.sub.2-4 alkylene group etc.; and Y represents a bond or a lower alkylene group, or salts thereof is useful as prophylactic or therapeutic agents of diseases related with melatonin activity.

  式##STR1##中的化合物，其中R.sup.1和R.sup.2分别代表H或一个可选择取代的碳氢基团；R.sup.3代表一个可选择取代的碳氢基团；R.sup.4代表H或一个碳氢基团；环A代表一个取代的苯环；X代表一个C.sub.2-4烷基基团等；Y代表键或一个较低的烷基基团，或其盐，可用作与褪黑激素活性相关的疾病的预防或治疗剂。
• BENZOCYCLOALKENE COMPOUNDS, THEIR PRODUCTION AND USE
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0781271A1

  公开（公告）日：1997-07-02
• BENZOCYCLOALKENE COMPOUNDS WITH MELATONINE RECEPTOR BINDING AFFINITY, THEIR PRODUCTION AND USE
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0848699B1

  公开（公告）日：2001-10-24
• US5922771A
  申请人：——

  公开号：US5922771A

  公开（公告）日：1999-07-13
• US6235789B1
  申请人：——

  公开号：US6235789B1

  公开（公告）日：2001-05-22