N-[2-(5-methoxy-1H-inden-3-yl)ethyl]propionamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: N-[2-(5-methoxy-1H-inden-3-yl)ethyl]propionamide
• 英文别名: N-[2-(6-methoxy-3H-inden-1-yl)ethyl]propanamide
• 化学式: C₁₅H₁₉NO₂
• 分子量: 245.321
• InChiKey: WGGZZJZSCAOORQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (2E)-2-(2,3-二氢-6-甲氧基-1H-茚-1-亚基)乙腈 在 钴 盐酸 、 氨 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 70.0 ℃ 、400.0 kPa 条件下， 反应 6.0h， 生成 N-[2-(5-methoxy-1H-inden-3-yl)ethyl]propionamide
  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.

  公式为##STR1##其中R.sup.1和R.sup.2分别代表H或可选取代的碳氢基团; R.sup.3代表可选取代的碳氢基团; R.sup.4代表H或碳氢基团; 环A代表取代苯环; X代表C.sub.2-4烷基等; Y代表键或较低的烷基，或其盐，可用作预防或治疗与褪黑激素活性相关的疾病的药物。
• BENZOCYCLOALKENE COMPOUNDS WITH MELATONINE RECEPTOR BINDING AFFINITY, THEIR PRODUCTION AND USE
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0848699A1

  公开（公告）日：1998-06-24
• US5922771A
  申请人：——

  公开号：US5922771A

  公开（公告）日：1999-07-13
• [EN] BENZOCYCLOALKENE COMPOUNDS WITH MELATONINE RECEPTOR BINDING AFFINITY, THEIR PRODUCTION AND USE<br/>[FR] COMPOSES DE BENZOCYCLOALCENE AYANT UNE AFFINITE DE LIAISON AU RECEPTEUR DE MELATONINE, PRODUCTION ET UTILISATION DE CES COMPOSES
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：WO1997005098A1

  公开（公告）日：1997-02-13

  (EN) A compound of formula (I) wherein R1 and R2 independently represent H or an optionally substituted hydrocarbon group; R3 represents an optionally substituted hydrocarbon group: R4 represents H or a hydrocarbon group; ring A represents a substituted benzene ring; X represents a C2-4 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.(FR) Cette invention concerne un composé de la formule (I) dans laquelle R1 et R2 représentent indépendamment H ou un groupe hydrocarbure éventuellement substitué; R3 représente un groupe hydrocarbure éventuellement substitué; R4 représente H ou un groupe hydrocarbure; le noyau A représente un noyau de benzène substitué; X représente un groupe alkylène C2-4, etc.; et Y représente une liaison ou un groupe alkylène inférieur. Cette invention concerne également les sels de ce composé, lequel peut être utilisé en qualité d'agent prophylactique ou thérapeutique contre des maladies liées à l'activité de la mélatonine.
• Synthesis of a Novel Series of Benzocycloalkene Derivatives as Melatonin Receptor Agonists
  作者：Kohji Fukatsu、Osamu Uchikawa、Mitsuru Kawada、Toru Yamano、Masayuki Yamashita、Koki Kato、Keisuke Hirai、Shuji Hinuma、Masaomi Miyamoto、Shigenori Ohkawa

  DOI：10.1021/jm020114g

  日期：2002.9.1

  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.