9-苄基-7-甲氧基-1-甲基吡啶并[3,4-b]吲哚 | 17019-04-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 中文名称: 9-苄基-7-甲氧基-1-甲基吡啶并[3,4-b]吲哚
• 英文名称: 1-(7-methoxy-1-methyl-β-carbolin-9-yl)-1-phenylmethane
• 英文别名: 9-benzyl-7-methoxy-1-methyl-β-carboline；9-benzyl-7-methoxy-1-methyl-9H-β-carboline；9-Benzyl-7-methoxy-1-methyl-9H-β-carbolin；9-Benzyl-7-methoxy-1-methyl-beta-carboline；9-benzyl-7-methoxy-1-methylpyrido[3,4-b]indole
• CAS: 17019-04-4
• 化学式: C₂₀H₁₈N₂O
• 分子量: 302.376
• InChiKey: NPVMXOVNSVOTAV-UHFFFAOYSA-N

物化性质

• 熔点：
  138-139 °C
• 沸点：
  512.1±50.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  9-苄基-7-甲氧基-1-甲基吡啶并[3,4-b]吲哚 生成 1-(9-benzyl-7-methoxy-9H-β-carbolin-1-ylmethyl)-2-methyl-cyclohexanol
  参考文献：
  名称：

  Certain substituted pyridindoles

  摘要：

  公开号：

  US02759000A1
• 作为产物：
  描述：

  四氢骆驼蓬碱 在 5%-palladium/activated carbon 、 sodium hydride 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 9-苄基-7-甲氧基-1-甲基吡啶并[3,4-b]吲哚
  参考文献：
  名称：

  N 9取代的香豆素衍生物作为潜在抗癌药的合成及生物学评价

  摘要：

  合成了一系列N 9取代的harmine衍生物，并评估了它们对一组癌细胞系的抗癌活性，它们的凋亡诱导作用以及它们的细胞周期效应。结果表明，N 9取代的甜菜碱衍生物具有抗癌作用。尤其是N 9-卤代烷基衍生物9a - 9c和N 9-酰基氨基甜菜碱衍生物11c和11d，其IC 50为值小于1μM的抗A-549和/或MCF-7细胞系的效力比阿霉素强。此外，结构-活性关系（SARs）表明，在甜菜碱的N 9位引入卤代烷基或苯磺酰基可以显着提高抗癌活性。活性最高的化合物（11d）导致细胞周期停滞在G2 / M期，并以剂量​​依赖性方式诱导细胞凋亡。

  DOI：

  10.1016/j.bmcl.2016.06.087

文献信息

• Structure-Based Design and Synthesis of Harmine Derivatives with Different Selectivity Profiles in Kinase versus Monoamine Oxidase Inhibition
  作者：Balázs Bálint、Csaba Wéber、Francisco Cruzalegui、Mike Burbridge、Andras Kotschy

  DOI：10.1002/cmdc.201600539

  日期：2017.6.21

  other hand, harmine is also a potent inhibitor of monoamine oxidase A (MAO-A). Using structure-based design, we synthesized a collection of harmine analogues with tunable selectivity toward these two enzymes. Modifications at the 7-position typically decreased affinity for DYRK1A, whereas substitution at the 9-position had a similar effect on MAO-A inhibition but DYRK1A inhibition was maintained. The resulting

  双特异性酪氨酸磷酸化调节激酶1A（DYRK1A）是一种新兴的生物学靶标，涉及多种治疗领域，例如神经系统疾病（尤其是唐氏综合症），代谢和肿瘤学。Harmine是一种在激酶中选择性抑制DYRK1A的天然产物，可以用作工具化合物，以更好地了解DYRK1A抑制作用引起的生物学过程。另一方面，harmine还是单胺氧化酶A（MAO-A）的有效抑制剂。使用基于结构的设计，我们合成了对这两种酶具有可调选择性的harmine类似物集合。在7位的修饰通常会降低对DYRK1A的亲和力，而在9位的取代对MAO-A的抑制作用相似，但仍保持DYRK1A的抑制作用。
• Synthesis and serum protein binding of novel ring-substituted harmine derivatives
  作者：Celesztina Domonkos、Ferenc Zsila、Ilona Fitos、Júlia Visy、Rudolf Kassai、Balázs Bálint、András Kotschy

  DOI：10.1039/c5ra06426k

  日期：——

  Potential anticancer derivatives of the β-carboline alkaloid harmine exhibit substituent dependent serum protein binding.

  β-羟基喹啉生物碱哈尔明的潜在抗癌衍生物显示取代基依赖的血清蛋白结合。
• Synthesis, acute toxicities, and antitumor effects of novel 9-substituted β-carboline derivatives
  作者：Rihui Cao、Qi Chen、Xuerui Hou、Hongsheng Chen、Huaji Guan、Yan Ma、Wenlie Peng、Anlong Xu

  DOI：10.1016/j.bmc.2004.06.038

  日期：2004.9

  A series of novel 9-substituted beta-carboline derivatives was synthesized from harmine and l-tryptophan, respectively. Cytotoxic activities of these compounds in vitro were investigated. The results showed that most compounds of 9-substituted beta-carboline derivatives had more remarkable cytotoxic activities in vitro than their corresponding parent compounds. Acute toxicities and antitumor effects

  分别从甜蜜素和色氨酸合成了一系列新颖的9-取代的β-咔啉衍生物。研究了这些化合物在体外的细胞毒活性。结果表明，大多数9-取代的β-咔啉衍生物的化合物在体外具有比其相应母体化合物更显着的细胞毒活性。还检查了选定的β-咔啉衍生物在小鼠中的急性毒性和抗肿瘤作用。结果表明，位置9处的短烷基或苄基取代基显着提高了抗肿瘤活性，位置3处的乙氧羰基或羧基取代基显着降低了这些β-咔啉衍生物的急性毒性和神经毒性。而且，与其他化合物相比，在第3位具有烷氧基羰基或羧基取代基且在第9位具有短烷基或苄基取代基的化合物均表现出更显着的抗肿瘤活性以及较低的急性毒性和神经毒性。发现分别在第9位和第3位具有正丁基和羧基取代基的化合物8c具有最高的抗肿瘤作用和最低的急性毒性和神经毒性。这些数据表明：（1）β-咔啉衍生物第9位和第3位的适当取代基可能在确定其增强的抗肿瘤活性以及降低的急性毒性和神经毒性作用方面起着至关重要的作用；
• Asian Immigrants' Reliance on Social Ties in a Multiethnic Labor Market
  作者：J. Sanders、V. Nee、S. Sernau

  DOI：10.1353/sof.2002.0058

  日期：2002.9.1

  We study how the social capital and closure properties of family- and ethnic-based social networks influence the incorporation of immigrants into their host society In so doing, we examine the relationship between immigrants' reliance on social ties and their employment. Data collected through ethnographic depth interviews of Asian immigrants in Los Angeles indicate that reliance on social ties usually operates informally, as when job seekers consult their more experienced and better-connected friends, relatives, and acquaintances and ask them to serve as intermediaries. These networks provide group-based resources that assist immigrants in making headway in their new society. Yet reliance on social ties is most common for moves into jobs of low occupational prestige that have low human capital requirements. Because of linguistic and cultural competence, immigrants who seek jobs from coethnic employers are often more self-reliant in the job search than those who seek work more broadly. In this way, ethnolinguistic closure encourages ethnic segmentation in the labor market. By contrast, reliance on social ties, another form of closure, facilitates job hunting in the wider domain of the labor market, where prospective employers may be of any ethnicity. Reliance on social ties thereby provides a mechanism by which immigrants gain employment throughout the multiethnic metropolitan labor market.

  我们研究了以家庭和种族为基础的社会网络的社会资本和封闭性如何影响移民融入东道国社会。在此过程中，我们研究了移民对社交关系的依赖与就业之间的关系。通过对洛杉矶的亚洲移民进行深入的种族学访谈收集的数据表明，对社交关系的依赖通常是非正式的，例如求职者咨询更有经验和人脉更广的朋友、亲戚和熟人，并请他们担任中介。这些网络提供的基于群体的资源有助于移民在新的社会中取得进展。然而，对社交关系的依赖最常见于职业声望低、人力资本要求低的工作。由于语言和文化能力，与那些更广泛地寻找工作的移民相比，那些向同族雇主求职的移民在求职时往往更自力更生。因此，种族语言封闭性鼓励劳动力市场的种族分割。相比之下，对社交关系的依赖是另一种封闭性，它有助于在更广泛的劳动力市场领域求职，因为潜在雇主可能是任何种族的人。因此，对社交关系的依赖为移民提供了在整个多民族大都市劳动力市场获得就业的机制。
• Exploring Kinase Inhibition Properties of 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine Derivatives
  作者：Yvonnick Loidreau、Carole Dubouilh-Benard、Marie-Renée Nourrisson、Nadège Loaëc、Laurent Meijer、Thierry Besson、Pascal Marchand

  DOI：10.3390/ph13050089

  日期：——

  We previously highlighted the interest in 6,5,6-fused tricyclic analogues of 4-aminoquinazolines as kinase inhibitors in the micromolar to the nanomolar range of IC50 values. For the generation of chemical libraries, the formamide-mediated cyclization of the cyanoamidine precursors was carried out under microwave irradiation in an eco-friendly approach. In order to explore more in-depth the pharmacological interest in such tricyclic skeletons, the central five member ring, i.e., thiophène or furan, was replaced by a pyrrole to afford 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine derivatives inspired from harmine. The inhibitory potency of the final products was determined against four protein kinases (CDK5/p25, CK1δ/ε, GSK3α/β, and DYRK1A). As a result, we have identified promising compounds targeting CK1δ/ε and DYRK1A and displaying micromolar and submicromolar IC50 values.

  我们先前强调了6,5,6-融合三环类4-氨基喹唑啉作为激酶抑制剂在微摩尔到纳摩尔范围内的IC50值的兴趣。为了生成化学库，使用甲酰胺介导的氰基胺前体的环化反应在微波辐射下进行，采用环保的方法。为了更深入地探索这种三环骨架的药理学兴趣，中心的五元环，即噻吩或呋喃，被替换为吡咯，以制备受到harmine启发的9H-嘧啶并[5,4-b]-和[4,5-b]吲哚-4-胺衍生物。最终产品的抑制效力被测定对四种蛋白激酶（CDK5/p25、CK1δ/ε、GSK3α/β和DYRK1A）。结果，我们已经确定了有前途的化合物，靶向CK1δ/ε和DYRK1A，显示微摩尔和亚微摩尔的IC50值。