外消旋-N-[2-(2,3-二氢-6-甲氧基-1H-茚-1-基)乙基]丙酰胺 | 178677-89-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 中文名称: 外消旋-N-[2-(2,3-二氢-6-甲氧基-1H-茚-1-基)乙基]丙酰胺
• 英文名称: (+/-)-N-[2-(6-methoxyindan-1-yl)ethyl]propanamide
• 英文别名: 1-[2-(propionylamino)ethyl]-6-methoxyindan；rac-N-[2-(2,3-Dihydro-6-methoxy-1H-inden-1-yl)ethyl]propanamide；N-[2-(6-methoxy-2,3-dihydro-1H-inden-1-yl)ethyl]propanamide
• CAS: 178677-89-9
• 化学式: C₁₅H₂₁NO₂
• 分子量: 247.337
• InChiKey: BURWKXUNJOXCGV-UHFFFAOYSA-N

物化性质

• 沸点：
  431.3±38.0 °C(Predicted)
• 密度：
  1.049±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、二氯甲烷、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  外消旋-N-[2-(2,3-二氢-6-甲氧基-1H-茚-1-基)乙基]丙酰胺 在 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-[2-(6-Isopropoxy-indan-1-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
• 作为产物：
  描述：

  (2E)-2-(2,3-二氢-6-甲氧基-1H-茚-1-亚基)乙腈 在 镍 氨 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 40.0 ℃ 、480.01 kPa 条件下， 生成 外消旋-N-[2-(2,3-二氢-6-甲氧基-1H-茚-1-基)乙基]丙酰胺
  参考文献：
  名称：

  合成一系列新的三环茚满衍生物作为褪黑激素受体激动剂。

  摘要：

  为了开发一种新的睡眠障碍治疗剂，我们合成了一系列新的三环茚满衍生物，并评估了它们与褪黑激素受体的结合亲和力。在我们以前的论文中，我们提出了甲氧基的构型，有利于MT（1）受体的结合。为了将甲氧基固定在一个活性构象中，我们决定合成构象受限的三环茚满类似物，将其在呋喃，1,3-二恶烷，恶唑，吡喃，吗啉或1,4-中的6-位氧原子合成二恶烷环系统。在这些化合物中，茚并[5,4-b]呋喃类似物被发现是最有效和最具选择性的MT（1）受体配体，并具有出色的代谢稳定性。取代基的优化导致（S）-（-）-22b，它对人MT（1）的亲和力非常强（K（i）= 0.014 nM），但对仓鼠MT（3）（）（K（i）= 2600 nM）或其他神经递质受体无明显亲和力。在实验动物中研究了（S）-（-）-22b的药理作用，发现以0.1 mg / kg的剂量po可以促进自由活动的猫的睡眠，如清醒性的降低和增加所表明的在慢波睡眠

  DOI：

  10.1021/jm0201159

文献信息

• Bicyclic compounds and pharmaceutical composition containing tricyclic compound for treating or preventing sleep disorders
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1199304A1

  公开（公告）日：2002-04-24

  A compound having the following general fomula: wherein R1 is an optionally substituted hydrocarbon, amino or heterocyclic group; R2 is H or an optionally substituted hydrocarbon group; R3 is H or an optionally substituted hydrocarbon or heterocyclic group; X is CHR4, NR4, O or S in which R4 is H or an optionally substituted hydrocarbon group; R5 is H, a halogen atom, C1-6 alkyl group, a C1-6 alkoxy group, a hydroxy group, a nitro group, a cyano group or an amino group wherein the C1-6 alkyl group, the C1-6 alkoxy group and the amino group may be substituted by 1 to 5 substituents, Y is C or N; ring B is an optionally substituted benzene ring; m = 1 to 4 and n = 0 to 2; L represents a leaving group such as a halogen atom, an alkylsulfonyl group, an alkylsulfonlyoxy group and arylsulfonyloxy group; or a salt thereof.

  具有以下一般式的化合物： 其中R1是可选择取代的碳氢化合物、氨基或杂环基团；R2是H或可选择取代的碳氢基团；R3是H或可选择取代的碳氢基团或杂环基团；X是CHR4、NR4、O或S，其中R4是H或可选择取代的碳氢基团；R5是H、卤素原子、C1-6烷基基团、C1-6烷氧基团、羟基、硝基、氰基或氨基，其中C1-6烷基基团、C1-6烷氧基团和氨基可能被1至5个取代基取代，Y是C或N；环B是可选择取代的苯环；m = 1至4，n = 0至2；L代表离去基团，如卤素原子、烷基磺酰基团、烷基磺酰氧基团和芳基磺酰氧基团；或其盐。
• Benzocycloalkene compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06235789B1

  公开（公告）日：2001-05-22

  A compound of the formula wherein R1 and R2 are H, a hydrocarbon group or a heterocyclic group, or R1 and R2 are combinedly a spiro ring; R3 is a hydrocarbon group, a substituted amino group, a substituted hydroxyl group or a heterocyclic group; R4 is H or alkyl; ring A is a substituted benzene ring; m and n denote 1 to 4; overscore (.........)} means a single or double bond or a salt, a process of producing thereof and a composition having a binding affinity for melatonin receptor.

  式中R1和R2为H、一个碳氢基团或一个杂环基团，或者R1和R2合并为一个螺环；R3为一个碳氢基团、一个取代氨基团、一个取代羟基团或一个杂环基团；R4为H或烷基；环A为一个取代苯环；m和n表示1到4；overscore (.........)}表示一个单键或双键或盐，一种生产方法及具有对褪黑激素受体具有结合亲和力的组合物。
• [EN] PHENYLPYRROLIDINE COMPOUNDS<br/>[FR] COMPOSÉS PHÉNYLPYRROLIDINIQUES
  申请人：FERRER INT

  公开号：WO2009053441A1

  公开（公告）日：2009-04-30

  This invention provides new phenylpyrrolidine compounds of general formula (I), their use for the treatment or prevention of melatoninergic disorders and its compositions.

  这项发明提供了一种新的苯基吡咯烷化合物，其通式为(I)，以及它们用于治疗或预防褪黑素功能失调及其组合物的用途。
• [EN] COMPOUNDS OF 2,3-DIHYDRO-BENZOFURAN<br/>[FR] COMPOSÉS DE 2,3-DIHYDROBENZOFURANE
  申请人：FERRER INT

  公开号：WO2009053444A1

  公开（公告）日：2009-04-30

  This invention provides new 2,3-dihydro-benzofuran compounds, their use for the treatment or prevention of melatoninergic disorders and its compositions.

  这项发明提供了新的2,3-二氢苯并呋喃化合物，其用于治疗或预防褪黑素失调及其组合物。
• Kinetic Resolutions of Indan Derivatives Using Bacteria
  作者：Naoki TARUI、Hayao WATANABE、Kohji FUKATSU、Shigenori OHKAWA、Kazuo NAKAHAMA

  DOI：10.1271/bbb.66.464

  日期：2002.1

  Racemic indan derivatives have been resolved by the hydrolysis of amide bonds using Corynebacterium ammoniagenes IFO12612 to produce (S)-amine and (R)-amides. In the kinetic resolution of 1 (N-[2-(6-methoxy-indan-1-yl)ethyl]acetamide), it was possible to run the reaction to 44% conversion on a 10-g scale, obtaining (S)-amine 4 ((S)-2-(6-methoxy-indan-1-yl)ethylamine) at >99% enantiomeric excess (ee) and (R)-1 at 98% ee.

  外消旋茚满衍生物通过水解酰胺键，利用氨化棒状杆菌 IFO12612 分离出(S)-胺和(R)-酰胺。在对 1（N-[2-(6-甲氧基-茚满-1-基)乙基]乙酰胺）进行动力学解析时，可以在 10 克的规模上将反应进行到 44% 的转化率，得到对映体过量率大于 99% 的 (S)-amine 4（(S)-2-(6-甲氧基-茚满-1-基)乙胺）和对映体过量率为 98% 的 (R)-1。