N-[2-(5-fluoro-1H-indol-3-yl)ethyl]acetamide | 2806-01-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-[2-(5-fluoro-1H-indol-3-yl)ethyl]acetamide
• 英文别名: N-acetyl-5-fluorotryptamine
• CAS: 2806-01-1
• 化学式: C₁₂H₁₃FN₂O
• 分子量: 220.246
• InChiKey: UDLASALUJLTGJV-UHFFFAOYSA-N

物化性质

• 熔点：
  125-126 °C
• 沸点：
  487.3±35.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-[2-(5-fluoro-1H-indol-3-yl)ethyl]acetamide 在 1-氟-2,4,6-三甲基吡啶三氟甲烷磺酸盐 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以80%的产率得到1-[(3aRS,8aSR)-3a,5-difluoro-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl]ethanone
  参考文献：
  名称：

  有用的程序将色胺和色胺醇衍生物进行氟环化为3a-氟吡咯并[2,3- b ]吲哚和3a-氟呋喃[2,3- b ]吲哚

  摘要：

  通用于各种色胺和色醇衍生物得到相应的3α-fluoropyrrolo [2.3-的fluorocyclization程序b ]吲哚和3a-fluorofuro [2.3- b ]吲哚，分别开发了采用Ñ氟-2,4,6-三甲基三氟甲磺酸酯（FP-T300）或的Selectfluor™作为电氟化剂。使用碳酸氢钠的3对fluorocyclization是有效地改善酸不稳定fluoropyrrolo（呋喃并）吲哚的产率。我们的程序是用于fluoropyrrolo（呋喃并）吲哚带有游离NH吲哚基团的合成特别有用。

  DOI：

  10.1016/j.jfluchem.2014.05.011
• 作为产物：
  描述：

  5-氟吲哚 在 乙酸铵 、 lithium aluminium tetrahydride 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 7.25h， 生成 N-[2-(5-fluoro-1H-indol-3-yl)ethyl]acetamide
  参考文献：
  名称：

  Spadoni, Gilberto; Balsamini, Cesarino; Bedini, Annalida, Medicinal Chemistry Research, 1998, vol. 8, # 9, p. 487 - 498

  摘要：

  DOI：

文献信息

• Mutasynthesis of Physostigmines in <i>Myxococcus xanthus</i>
  作者：Lea Winand、Pascal Schneider、Sebastian Kruth、Nico-Joel Greven、Wolf Hiller、Marcel Kaiser、Jörg Pietruszka、Markus Nett

  DOI：10.1021/acs.orglett.1c02374

  日期：2021.8.20

  The alkaloid physostigmine is an approved anticholinergic drug and an important lead structure for the development of novel therapeutics. Using a complementary approach that merged chemical synthesis with pathway refactoring, we produced a series of physostigmine analogues with altered specificity and toxicity profiles in the heterologous host Myxococcus xanthus. The compounds that were generated by

  生物碱毒扁豆碱是一种经批准的抗胆碱能药物，也是开发新疗法的重要先导结构。使用将化学合成与通路重构相结合的互补方法，我们在异源宿主Myxococcus xanthus 中产生了一系列具有改变的特异性和毒性特征的毒扁豆碱类似物。通过应用简单的喂养策略产生的化合物包括有前途的候选药物苯丝林，以前只能通过全合成获得。
• Structure-activity relationships for substrates and inhibitors of pineal 5-hydroxytryptamine-N-acetyltransferase: preliminary studies
  作者：Shuren Shen、Béatrice Brémont、Isabelle Serraz、Jean Andrieux、Annie Poncet、Monique Mathé-Allainmat、Evelyne Chanut、Jean-Hugues Trouvin、Michel Langlois

  DOI：10.1016/0014-2999(96)00228-2

  日期：1996.6

  derivatives and no clear structure-activity relationship was observed. Melatonin and several bioisosteric derivatives were shown to be inhibitors of 5-HT-N-acetyltransferase. Preliminary data suggested that over the 5-50-microM concentration range, melatonin was a competitive inhibitor (IC50 = 10 microM) with a concentration-dependent inhibitory effect on its own synthesis in the pineal gland. However, the

  色胺，（1-萘基）乙胺和苯乙胺衍生物作为绵羊松果体5-羟色胺-N-乙酰基转移酶（5-HT-NAT）的底物进行了测试，后者是褪黑素合成的关键酶。几乎所有的吲哚衍生物都具有与色胺类似的亲和力（Km = 0.05 mM），而取代的萘和苯基衍生物的效价较低。但是，Km值似乎受取代基的位阻和极性性质影响。萘和苯基衍生物的Vmax值通常比吲哚衍生物的Vmax值高10-20倍，并且未观察到明确的结构活性关系。褪黑激素和几种生物等位衍生物被证明是5-HT-N-乙酰基转移酶的抑制剂。初步数据表明，在5-50 microM的浓度范围内，褪黑激素是一种竞争性抑制剂（IC50 = 10 microM），对松果体自身的合成具有浓度依赖性的抑制作用。然而，生物等位萘衍生物被表征为混合抑制剂。公认的褪黑素能拮抗剂（1-萘基）乙基乙酰氨基也被证明是5-HT-N-乙酰基转移酶的抑制剂（IC50 = 8 microM），是调
• [EN] MELATONIN DERIVATIVES AND THEIR USE FOR TREATING NEUROLOGICAL DYSFUNCTIONS<br/>[FR] DERIVES DE MELATONINE ET LEUR UTILISATION DANS LE TRAITEMENT DE DYSFONCTIONNEMENTS NEUROLOGIQUES
  申请人：FAUST PHARMACEUTICALS

  公开号：WO2004085392A1

  公开（公告）日：2004-10-07

  The present invention relates to compounds of the general formula (1): wherein R1, R2, R3, R4 and R5 are H or a moiety of the formula : -(R6)n-R7; with R6 is a is an alkyl chain and R7 is, a moiety selected in the group consisting of -Cn,H2n2,+I, a cycloalkyl moiety, -N(Cn,H2n,+I)(Cn,H2n,+1), -NH-cycloalkyl, -O(Cn,H2n'+I), -0-cycloalkyl, =O, =S, -NO2, -I, -Br, -Cl, -F, -CF3, -OCF3, -COOH, -S03H, -P03H2, -CN, A3 and A4 are, C, N,O or S;m is from 0 to 2; and to their use for the treatment and/or prevention of diseases and conditions mediated by the imbalance of acetylcholine, and for treating and/or preventing glutamate excitotoxicity.

  本发明涉及通式（1）的化合物：其中R1、R2、R3、R4和R5为H或具有以下结构的基团：-(R6)n-R7；其中R6是烷基链，R7是在由-CnH2n2，+I组成的基团中选择的一个基团，是环烷基基团，-N(CnH2n+I)(CnH2n+1)，-NH-环烷基，-O(CnH2n'+I)，-O-环烷基，=O，=S，-NO2，-I，-Br，-Cl，-F，-CF3，-OCF3，-COOH，-SO3H，-PO3H2，-CN中的一种；A3和A4为C、N、O或S；m为0到2；以及它们用于治疗和/或预防由乙酰胆碱失衡介导的疾病和症状，以及用于治疗和/或预防谷氨酸兴奋毒性。
• Vinylogous acid derivatives
  申请人：Banner David

  公开号：US20070129421A1

  公开（公告）日：2007-06-07

  The invention is concerned with vinylogous acids derivatives of formula (I) wherein A and R 1 to R 6 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit chymase and can be used as medicaments.

  本发明涉及式(I)的烯丙基酸衍生物，其中A和R1到R6如说明书和权利要求所定义，以及其生理上可接受的盐。这些化合物抑制chymase并可用作药物。
• Melatonin Receptor Ligands:  Synthesis of New Melatonin Derivatives and Comprehensive Comparative Molecular Field Analysis (CoMFA) Study
  作者：Marco Mor、Silvia Rivara、Claudia Silva、Fabrizio Bordi、Pier Vincenzo Plazzi、Gilberto Spadoni、Giuseppe Diamantini、Cesarino Balsamini、Giorgio Tarzia、Franco Fraschini、Valeria Lucini、Romolo Nonno、Bojidar Michaylov Stankov

  DOI：10.1021/jm9810093

  日期：1998.9.1

  The CoMFA methodology was applied to melatonin receptor ligands in order to establish quantitative structure-affinity relationships. One hundred thirty-three compounds were considered: they were either collected from literature or newly synthesized in order to gain information about the less explored positions. To this end, various melatonin derivatives were prepared and their affinity for quail optic tecta melatonin receptor was tested. Compounds were aligned on the putative active conformation of melatonin proposed by our previously reported pharmacophore search, and their relative affinities were calculated from the displacement of 2-[I-125]-iodomelatonin on different tissues expressing aMT receptors. Compounds were grouped into three sets according to their topology. Subset A: melatonin-like compounds; subset B: N-acyl-2-amino-8-methoxytetralins and related compounds; subset C: N-acyl-phenylalkylamines and related compounds. CoMFA models were derived for each set, using the steric, electrostatic, and lipophilic fields as structural descriptors; the PLS analyses were characterized by good statistical parameters, taking into account the heterogeneity of the binding data, obtained with different experimental protocols. From the CoMFA model for the melatonin-like compounds, besides the well-known positive effect of 2-substitution, a low steric tolerance for substituents in 1, 6, and 7, and a negative effect of electron-rich 4-substituents were observed; the information provided by the newly synthesized compounds was essential for these results. Moreover, a comprehensive model for the 133 compounds, accounting for a common alignment and a common mode of interaction at the melatonin receptor, was derived (Q(2) = 0.769, R-2 = 0.905). This model validates our previously reported pharmacophore search and offers a clear depiction of the structure-affinity relationships for the melatonin receptor ligands.