N-乙酰基-5-氯色胺 | 79087-58-4

• 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
• 中文名称: N-乙酰基-5-氯色胺
• 英文名称: N-Acetyl-5-Chloro-Tryptamine
• 英文别名: N-[2-(5-chloro-1H-indol-3-yl)ethyl]acetamide
• CAS: 79087-58-4
• 化学式: C₁₂H₁₃ClN₂O
• mdl: MFCD00458332
• 分子量: 236.701
• InChiKey: WJIFPSFOSMKSAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 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：
  1

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  5-氯靛胺盐酸盐	5-chlorotryptamine	3764-94-1	C10H11ClN2	194.664
  ——	Nb-acetyl-1-hydroxytryptamine	136788-90-4	C12H14N2O2	218.255
  ——	N(b)-acetyl-1-methoxytryptamine	98258-88-9	C13H16N2O2	232.282

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	tert-butyl N-acetyl-N-[2-(5-chloro-1H-indol-3-yl)ethyl]carbamate	1161079-82-8	C17H21ClN2O3	336.818

反应信息

• 作为反应物：
  描述：

  N-乙酰基-5-氯色胺 在 四(三苯基膦)钯 、 potassium acetate 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 19.0h， 生成 N-[2-(11-Chloro-6,7-dihydro-5H-benzo[3,4]azepino[1,2-a]indol-13-yl)-ethyl]-acetamide
  参考文献：
  名称：

  Mapping the Melatonin Receptor. 6. Melatonin Agonists and Antagonists Derived from 6H-Isoindolo[2,1-a]indoles, 5,6-Dihydroindolo[2,1-a]isoquinolines, and 6,7-Dihydro-5H-benzo[c]azepino[2,1-a]indoles

  摘要：

  6H-Isoindolo[2,1-a]indoles (5, 7, 10, 13), 5,6-dihydroindolo[2,1-a]isoquinolines (20, 21), and 6,7-dihydro-5H-benzo[c]azepino[2,1-a]indoles (23, 25, 27, 30) have been prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor. The affinity of analogues was determined in a radioligand binding assay using cloned human mt(1) and MT2 receptor subtypes expressed in NIH 3T3 cells. Agonist and antagonist potency was measured using the pigment aggregation response of a clonal line of Xenopus laevis melanophores. The 2-methoxyisoindolo[2,1-a]indoles (7a-d) showed much higher binding affinities than the parent isoindoles (5a-e), and whereas 7a-c were agonists in the functional assay, 7d and 5a-e were antagonists. The 2-ethoxyisoindolo[2,1-a]indoles (10a-d) showed reduced binding affinities compared to their methoxy analogues, while the 5-chloro derivative 13 showed a considerable reduction in binding affinity and potency compared to 7a. The 10-methoxy-5,6-dihydroindolo[2,1-a]isoquinolines (21a-c) had higher binding affinities than the corresponding parent indoloisoquinolines (20a-c) in the human receptor subtypes, and the parent compounds were antagonists whereas the 10-methoxy derivatives were agonists in the functional assay. The N-cyclobutanecarbonyl derivatives of both the parent (20d) and 10-methoxyl (21d) series had similar binding affinities and were both antagonists with similar potencies. The 11-methoxy-6,7-5H-benzo[c]azepino[2,1-a]indoles (25a-d) had higher binding affinities than the corresponding parent compounds (23a-d) at the MT2 receptor but similar affinities at the mt(1) site; all of the compounds were antagonists in the functional assay. Changing 11-methoxy for 11-ethoxy decreased the binding affinity slightly, and this was more evident at the MT2 receptor. All of the derivatives investigated had either the same or a greater affinity for the human MT2 receptor compared to the mt(1) receptor (range 1:1-1:132). This suggests that the mt(1) and MT2 receptor pockets differ in their ability to accommodate alkyl groups in the indole nitrogen region of the melatonin molecule. Two compounds (7c and 25c) were tested in functional assays on recombinant mt(1) and MT2 melatonin receptors. Compound 7c is a potent agonist with some selectivity (44-fold) for the MT2 receptor, while 25c is an MT2-preferring antagonist. Increasing the carbon chain length between N-1 of indole and the 2-phenyl group from n = 1 through n = 3 leads to a fairly regular decrease in the binding affinity, but, remarkably, when n = 3, it converts the methoxy compounds from melatonin agonists to antagonists. The Xenopus melatonin receptor thus cannot accommodate an N-n-alkyl chain attached to a 2-phenyl substituent with n > 2 in the required orientation to induce or stabilize the active receptor conformation.

  DOI：

  10.1021/jm980684+
• 作为产物：
  描述：

  Nb-acetyl-1-hydroxytryptamine 在 盐酸 、 4-二甲氨基吡啶 作用下， 以 甲醇 、 水 为溶剂， 反应 17.0h， 生成 N-乙酰基-5-氯色胺
  参考文献：
  名称：

  A Novel Methodology for Preparing 5-Chloro- and 5-Bromotryptamines and Tryptophanes, and Its Application to the Synthesis of (±)-Bromochelonin B

  摘要：

  DOI：

  10.3987/com-99-8721

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。
• Iridium-Catalyzed Direct Synthesis of Tryptamine Derivatives from Indoles: Exploiting N-Protected β-Amino Alcohols as Alkylating Agents
  作者：Silvia Bartolucci、Michele Mari、Annalida Bedini、Giovanni Piersanti、Gilberto Spadoni

  DOI：10.1021/acs.joc.5b00195

  日期：2015.3.20

  The selective C3-alkylation of indoles with N-protected ethanolamines involving the “borrowing hydrogen” strategy is described. This method provides convenient and sustainable access to several tryptamine derivatives.

  描述了涉及“借用氢”策略的N-保护的乙醇胺对吲哚的选择性C3-烷基化反应。该方法提供了对几种色胺衍生物的方便且可持续的获取途径。
• 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
• Complementary Site‐Selective Halogenation of Nitrogen‐Containing (Hetero)Aromatics with Superacids
  作者：Alexander Mamontov、Agnès Martin‐Mingot、Benoit Métayer、Omar Karam、Fabien Zunino、Fodil Bouazza、Sébastien Thibaudeau

  DOI：10.1002/chem.202000902

  日期：2020.8.17

  functionalization of arenes that is complementary to classical aromatic substitution reactions remains a long‐standing quest in organic synthesis. Exploiting the generation of halenium ion through oxidative process and the protonation of the nitrogen containing function in HF/SbF5, the chlorination and iodination of classically inert Csp2−H bonds of aromatic amines occurs. Furthermore, the superacid‐promoted (poly)protonation

  与经典的芳香族取代反应互补的芳烃的位点选择性官能化仍然是有机合成中的长期追求。通过利用氧化过程中的ion离子的产生和HF / SbF 5中含氮功能的质子化，芳香胺的经典惰性Csp 2 -H键发生氯化和碘化。此外，分子的超强酸促进（聚）质子化作用起到保护作用，有利于天然生物碱和活性药物成分的后期选择性卤化
• [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。