5-甲氧基-N-环丙酰基色胺 | 139564-01-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 5-甲氧基-N-环丙酰基色胺
• 英文名称: S 20760
• 英文别名: N-[2-(5-methoxyindol-3-yl)ethyl]-cyclopropylcarboxamide；N-cyclopropanoyl-5-methoxytryptamine；N-[2-(5-methoxy-1H-indol-3-yl)ethyl]cyclopropanecarboxamide
• CAS: 139564-01-5
• 化学式: C₁₅H₁₈N₂O₂
• 分子量: 258.32
• InChiKey: HSOHROOUHRUSJR-UHFFFAOYSA-N

物化性质

• 沸点：
  548.8±38.0 °C(Predicted)
• 密度：
  1.248±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-甲氧基-N-环丙酰基色胺 在 四(三苯基膦)钯 、 potassium acetate 、 sodium hydride 作用下， 以 四氢呋喃 、 二甲胺 为溶剂， 反应 19.0h， 生成 N-[2-(11-methoxy-6,7-dihydro-5H-indolo[2,1-a][2]benzazepin-13-yl)ethyl]cyclopropanecarboxamide
  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：

  5-甲氧基色胺 、 环丙基甲酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以90%的产率得到5-甲氧基-N-环丙酰基色胺
  参考文献：
  名称：

  2-取代的5-甲氧基-N-酰基草胺：合成，对褪黑激素受体的结合亲和力和生物活性评估。

  摘要：

  合成了一系列的2-取代的5-甲氧基-N-酰基草胺，并使用2- [125I]碘酮在一系列体外配体-受体结合实验中测试了它们与从鹌鹑全脑分离的褪黑激素受体的亲和力。作为标记的配体。C2取代基和N-酰基的最优化产生对受体具有皮摩尔亲和力的化合物（对褪黑激素具有纳摩尔亲和力的化合物）。在两项评估生物学活性的测试中（对兔顶叶皮层中单个神经元的自发放电活性的影响，以及体内的叙利亚仓鼠性腺回归模型），大多数类似物均起激动剂的作用。单独在C2处进行异丙基取代，或在N-酰基位置上同时进行环丙基取代，会导致亲和力低得多，且生物学作用较弱，或在后一种情况下缺乏活动。令人感兴趣的是化合物4d（R =苯基，R1 = CH3）和4g（R =苯基，R1 =环丙基），尽管使用类似物，但在所用实验模型的条件下对受体具有很高的亲和力并具有明显的拮抗活性。 4 g（R =苯基，（R1 =环丙基）似乎是一种弱拮抗剂，并且在较高浓

  DOI：

  10.1021/jm00077a010

文献信息

• Synthesis and Structure-Activity Relationships of Novel Naphthalenic and Bioisosteric Related Amidic Derivatives as Melatonin Receptor Ligands
  作者：Patrick Depreux、Daniel Lesieur、Hamid Ait Mansour、Peter Morgan、H. Edward Howell、Pierre Renard、Daniel-Henri Caignard、Bruno Pfeiffer、Philippe Delagrange

  DOI：10.1021/jm00046a006

  日期：1994.9

  of these ligands give biphasic dose-response curves which suggests that there may be two melatonin receptor subtypes within the ovine pars tuberalis cells. The replacement of naphthalene by benzofuran or benzothiophene did not strongly alter the affinity for the melatonin receptor. In contrast, the benzimidazole analogue was a poor ligand. Compound 7, the naphthalenic analogue of melatonin, a selective

  合成了一系列 N-萘乙基酰胺衍生物并作为褪黑激素受体配体进行了评估。每种化合物对褪黑激素受体的亲和力通过使用[2-125I]碘褪黑激素对绵羊结节膜匀浆的结合研究来确定。构效关系得出结论，萘是褪黑激素吲哚部分的生物等排体。此外，似乎亲和力受到酰胺官能团氮的取代基大小的强烈影响。许多这些配体给出了双相剂量反应曲线，这表明绵羊结节细胞内可能存在两种褪黑激素受体亚型。用苯并呋喃或苯并噻吩代替萘并没有强烈改变对褪黑激素受体的亲和力。相比之下，苯并咪唑类似物是一种较差的配体。化合物 7，褪黑激素的萘类似物，褪黑激素受体的选择性配体和激动剂衍生物，已被选择用于临床开发。
• Compounds effective in the treatment of circadian rhythms and related
  申请人：Instituto Farmacologico Lombardo-IFLO, S.a.S.

  公开号：US05552428A1

  公开（公告）日：1996-09-03

  The novel compounds of formula: ##STR1## in which R is isopropyl, cyclohexyl, phenyl, CH.sub.3, Br or I; or H R.sub.1 is CH.sub.3 or cyclopropyl and R.sub.2 is H or Br, and when R.sub.1 is cyclopropyl and R.sub.2 is H, R is other than H, and when R.sub.1 is CH.sub.3 and R.sub.2 is H, R is other than H, and when R.sub.1 is CH.sub.3 and R.sub.2 is H, R is other than I, and when R is CH.sub.3 and R.sub.2 is H, R.sub.1 is other than CH.sub.3, and when R is phenyl and R.sub.2 is H, R.sub.1 is other than CH.sub.3, exhibit superior activity in the treatment of pathologies which interfere with the circadian rhythm. A novel method of preparation is described according to which the pharmaceutical compositions containing the novel compounds, as well as compounds already known, are administered transdermally. The novel method of administration results in sustained peripheral blood level. Novel pharmaceutical compositions are described suitable for transdermal administration.

  该公式的新化合物为：##STR1##，其中R为异丙基、环己基、苯基、CH.sub.3、Br或I；或HR.sub.1为CH.sub.3或环丙基，R.sub.2为H或Br，当R.sub.1为环丙基且R.sub.2为H时，R不是H，当R.sub.1为CH.sub.3且R.sub.2为H时，R不是H，当R.sub.1为CH.sub.3且R.sub.2为H时，R不是I，当R为CH.sub.3且R.sub.2为H时，R.sub.1不是CH.sub.3，当R为苯基且R.sub.2为H时，R.sub.1不是CH.sub.3，表现出在干扰昼夜节律的病变治疗中具有优越活性。根据所述的一种新制备方法，含有新化合物的药物组合物以及已知的化合物经皮途径给药。新的给药方法导致持续的外周血药浓度水平。描述了适用于经皮给药的新型药物组合物。
• Arylethylamine compounds
  申请人：Adir et Compagnie

  公开号：US05276051A1

  公开（公告）日：1994-01-04

  The invention relates to a compound selected from those of formula (I): ##STR1## in which Ar', R.sub.1 and R.sub.2 are as defined in the specification, an optical isomer, and an addition salt thereof with a pharmaceutically-acceptable acid or base. Medicinal product which is useful in treating or in preventing a disorder of the melatoninergic system.

  该发明涉及一种从以下化合物中选择的化合物（I）：##STR1##其中Ar'、R1和R2如规范中所定义，光学异构体，以及其与药用可接受酸或碱的加合盐。用于治疗或预防褪黑素系统紊乱的药物产品。
• Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions
  申请人：Kõster Hubert

  公开号：US20100248264A1

  公开（公告）日：2010-09-30

  Capture compounds and collections thereof and methods using the compounds for the analysis of biomolecules are provided. In particular, collections, compounds and methods are provided for analyzing complex protein mixtures, such as the proteome. The compounds are multifunctional reagents that provide for the separation and isolation of complex protein mixtures. Automated systems for performing the methods also are provided.

  提供了捕获化合物及其集合以及使用这些化合物进行生物分子分析的方法。特别地，提供了用于分析复杂蛋白质混合物（如蛋白质组）的集合、化合物和方法。这些化合物是多功能试剂，可用于分离和分离复杂的蛋白质混合物。还提供了执行这些方法的自动化系统。
• Novel naphthalenic ligands with high affinity for the melatonin receptor
  作者：S. Yous、J. Andrieux、H. E. Howell、P. J. Morgan、P. Renard、B. Pfeiffer、D. Lesieur、B. Guardiola-Lemaitre

  DOI：10.1021/jm00086a018

  日期：1992.4