(R)-N-[2-(6-methoxyindan-1-yl)ethyl]acetamide | 178678-03-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (R)-N-[2-(6-methoxyindan-1-yl)ethyl]acetamide
• 英文别名: (R)-1-[2-(acetylamino)ethyl]-6-methoxyindan；N-[2-[(1R)-6-methoxy-2,3-dihydro-1H-inden-1-yl]ethyl]acetamide
• CAS: 178678-03-0
• 化学式: C₁₄H₁₉NO₂
• 分子量: 233.31
• InChiKey: UOVGAGSCHHZUPU-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  (R)-N-[2-(6-methoxyindan-1-yl)ethyl]acetamide 在 sodium hydroxide 、 一水合肼 作用下， 以 四氢呋喃 为溶剂， 反应 26.0h， 生成 (R)-N-[2-(6-methoxy-2,3-dihydro-1H-inden-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：

  (E)-N-[2-(6-methoxyindan-1-ylidene)-ethyl]acetamide 以 甲醇 为溶剂， 以82%的产率得到(R)-N-[2-(6-methoxyindan-1-yl)ethyl]acetamide
  参考文献：
  名称：

  Tricyclic compounds, their production and use

  摘要：

  该化合物的结构式为：##STR1## 其中R.sup.1是可选择取代的碳氢化合物、氨基或杂环基团；R.sup.2是H或可选择取代的碳氢基团；R.sup.3是H或可选择取代的碳氢或杂环基团；X是CHR.sup.4、NR.sup.4、O或S，其中R.sup.4是H或可选择取代的碳氢基团；Y是C、CH或N；环A是可选择取代的5-至7-成员环；环B是可选择取代的苯环；m为1至4，或其盐，提供了其制备方法、生产中间体和包含它的药物组合物。

  公开号：

  US06034239A1

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。
• 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。
• [EN] TRICYCLIC COMPOUNDS, THEIR PRODUCTION AND USE<br/>[FR] COMPOSES TRICYCLIQUES, LEUR PRODUCTION ET LEUR UTILISATION
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：WO1997032871A1

  公开（公告）日：1997-09-12

  (EN) A compound of formula (I) 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; Y is C, CH or N; ring A is an optionally substituted 5- to 7-membered ring; ring B is an optionally substituted benzene ring; and m is 1 to 4, or a salt thereof, a process for producing it, an intermediate for the production and a pharmaceutical composition comprising it are provided.(FR) L'invention concerne un composé de la formule (I) dans laquelle R1 est un groupe hydrocarbure, amino ou hétérocyclique, éventuellement substitué; R2 est H ou un groupe hydrocarbure, éventuellement substitué; R3 est H ou un groupe hydrocarbure ou hétérocyclique, éventuellement subsitué; X est CHR4, NR4, O ou S, où R4 est H ou un groupe hydrocarbure éventuellement substitué; Y est C, CH ou N; A est un cycle à 5 - 7 éléments, éventuellement substitué; B est un cycle benzénique, éventuellement substitué; et m est compris entre 1 et 4. L'invention concerne également un sel de ce composé, un procédé pour le produire, un intermédiaire utile pour cette production et une composition pharmaceutique contenant ce composé.

  化合物的化学式(I)其中R1是一个可选的取代的碳氢化合物，氨基或杂环基团；R2是H或一个可选的取代的碳氢基团；R3是H或一个可选的取代的碳氢化合物或杂环基团；X是CHR4，NR4，O或S，其中R4是H或一个可选的取代的碳氢基团；Y是C，CH或N；环A是一个可选的取代的5-7元环；环B是一个可选的取代的苯环；m为1至4，或其盐，提供了制备它的过程，制备的中间体以及包含它的制药组合物。
• Bicyclic intermediates
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1550655A1

  公开（公告）日：2005-07-06

  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.

  具有以下通式的化合物： 其中 R1 是任选取代的烃基、氨基或杂环基； R2 是 H 或任选取代的烃基； R3 是 H 或任选取代的烃基或杂环基； X 是 CHR4、NR4、O 或 S，其中 R4 是 H 或任选取代的烃基；R5 是 H、卤素原子、C1-6 烷基、C1-6 烷氧基、羟基、硝基、氰基或氨基，其中 C1-6 烷基、C1-6 烷氧基和氨基可被 1 至 5 个取代基取代，Y 是 C 或 N；环 B 是任选取代的苯环；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、烷基磺酰氧基和芳基磺酰氧基；或其盐。