N-(2-aminoethyl)-1-(4-methoxyphenyl)-9H-β-carboline-3-amide | 1401863-26-0

• 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
• 英文名称: N-(2-aminoethyl)-1-(4-methoxyphenyl)-9H-β-carboline-3-amide
• 英文别名: N-(2-aminoethyl)-1-(4-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide
• CAS: 1401863-26-0
• 化学式: C₂₁H₂₀N₄O₂
• 分子量: 360.415
• InChiKey: BWUNSTMRJXJIPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  93
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-aminoethyl)-1-(4-methoxyphenyl)-9H-β-carboline-3-amide 在 sodium hydroxide 作用下， 以 水 、 乙腈 为溶剂， 反应 49.0h， 生成 N-{2-[(4,6-bis(isopropylamino)-1,3,5-triazin-2-yl)amino]ethyl}-1-(4-methoxyphenyl)-β-carboline-3-carboxamide
  参考文献：
  名称：

  Synthesis, antileishmanial activity and mechanism of action studies of novel β-carboline-1,3,5-triazine hybrids

  摘要：

  A series of novel hybrids beta-carboline-1,3,5-triazine were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania amazonensis. Among the compounds tested, the hybrids 9d, 9e, 16a and 16b showed potent activity against the promastigote forms with IC50 values less than 8 mu M. Compounds 9e and 1611) were also active against amastigote forms, displaying IC50 values of 1.0 +/- 0.1 mu M and 1.2 +/- 0.51 mu M, respectively. Besides that, the hybrid 16b bearing the 4-methoxyphenyl group at C-1 of beta-carboline and isopropylamino group at 1,3,5-triazine, showed low toxicity, being 23.5 and 121.4 times more toxic for promastigotes and axenic amastigotes, respectively, than for macrophage J774-A1 cell lines. Investigation of action mechanism in promastigotes showed that compound 16b caused alterations in cell division cycle and an increase of lipid-storage bodies, leading the cells to death through various factors. The accumulation of lipid bodies may be associated with apoptotic cell death. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.014
• 作为产物：
  描述：

  L-色氨酸 在 potassium permanganate 、 氯化亚砜 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2-aminoethyl)-1-(4-methoxyphenyl)-9H-β-carboline-3-amide
  参考文献：
  名称：

  作为 NAD(P)H 的新型 β-咔啉基吲哚-4,7-醌衍生物：醌氧化还原酶-1 抑制剂，通过诱导活性氧、细胞凋亡和 DNA 损伤具有有效的抗肿瘤活性。

  摘要：

  设计并合成了18 种新的基于 β-咔啉的吲哚-4,7-醌衍生物（12a-i和13a-i），并研究了它们的体外和体内抗增殖活性。大多数目标化合物对三种人类肿瘤细胞的增殖表现出强烈的抑制作用。特别是，活性最强的化合物13g不仅显示出比临床抗肿瘤候选药物 β-拉帕酮更显着的抗增殖活性，而且还发挥了显着的 NAD(P)H：醌-氧化还原酶-1 (NQO1) 抑制活性和 NQO1 依赖性细胞毒性在 HT29 细胞中。此外，13g剂量依赖性地诱导 HT29 细胞中的高 ROS 水平，并在体外选择性抑制癌细胞但不抑制非肿瘤结肠细胞增殖。重要的是，13g通过调节相对凋亡蛋白和 H2AX 表达促进 HT29 细胞凋亡和 DNA 损伤。最后，13g在小鼠中显示出对 HT29 人结肠直肠腺癌异种移植物的显着生长抑制，而没有明显的毒性。

  DOI：

  10.1111/cbdd.13752

文献信息

• [EN] COMPOUNDS FOR TREATMENT OF METABOLIC SYNDROME<br/>[FR] COMPOSÉS POUR LE TRAITEMENT DU SYNDROME MÉTABOLIQUE
  申请人：SJT MOLECULAR RES S L

  公开号：WO2012130912A1

  公开（公告）日：2012-10-04

  Present invention refers to new compounds of formula I or II, its synthesis and its use in the treatment of metabolic syndrome, particularly for the treatment of type I or type II diabetes and/or metabolic syndrome or metabolic disease or metabolic disorders.

  本发明涉及公式I或II的新化合物，其合成以及在治疗代谢综合征中的应用，特别是用于治疗I型或II型糖尿病和/或代谢综合征或代谢疾病或代谢紊乱。
• 含取代β-咔啉结构的三氟甲基吡唑酰胺及其制备方法和应用
  申请人：南通大学

  公开号：CN111961048B

  公开（公告）日：2022-05-13

  本发明涉及含取代β‑咔啉结构的三氟甲基吡唑酰胺(I)及其制备方法和应用。经过三氟甲基吡唑甲酰基氯与取代β‑咔啉的反应得到。所述含取代β‑咔啉结构的三氟甲基吡唑酰胺对肿瘤细胞表现出良好抑制作用，该化合物可用于制备抗肿瘤细胞药物。
• 含取代吡唑和β-咔啉单元的双酰胺类化合物的制备与应用
  申请人：南通大学

  公开号：CN111875605B

  公开（公告）日：2022-08-09

  本发明涉及含取代吡唑和β‑咔啉单元的双酰胺类化合物I的制备与应用。通过β‑咔啉化合物与1‑甲基‑3‑取代基‑4‑氯吡唑‑5‑羰基氯的缩合而成。所述含取代吡唑和β‑咔啉单元的双酰胺类化合物对肿瘤细胞有优良的抗肿瘤效果，该化合物可以用来制备抗肿瘤细胞药物。
• Compounds for use in the prevention and/or treatment of non-alcoholic fat liver disease and non-alcoholic steatohepatitis
  申请人：SJT MOLECULAR RESEARCH, SL

  公开号：US10857136B2

  公开（公告）日：2020-12-08

  Compounds of formula I, and their pharmaceutical and food grade acceptable salts, for use in the prevention and/or treatment of NAFLD (non-alcoholic fat liver disease) or NASH (non-alcoholic steatohepatitis), and related symptoms and/or associated pathologies thereof are described. Also described are pharmaceutical compositions or nutraceutical compositions comprising said compounds of formula I, and their pharmaceutically, or food grade, acceptable or allowable, salts and combinations thereof, optionally with any inert ingredient, carrier, excipient or alike for use in the prevention and/or treatment of NAFLD or NASH, and related symptoms and/or associated pathologies thereof. Additionally described are methods for the prevention and/or treatment of NAFLD or NASH, and related symptoms and/or associated pathologies thereof comprising the administration to a subject in need thereof, of any compound of formula I, and pharmaceutical and food grade acceptable salts thereof, or any pharmaceutical compositions, functional food additives or nutraceutical compositions comprising the same.

  式 I 的化合物、 描述了用于预防和/或治疗非酒精性脂肪肝（NAFLD）或非酒精性脂肪性肝炎（NASH）及其相关症状和/或相关病理的式 I 化合物及其药用和食品级可接受盐。还描述了药物组合物或营养保健品组合物，其包含所述式 I 化合物及其药学上或食品级可接受或允许的盐及其组合，可选地与任何惰性成分、载体、赋形剂或类似物一起用于预防和/或治疗非酒精性脂肪肝或 NASH 及其相关症状和/或相关病理。此外，还描述了预防和/或治疗非酒精性脂肪肝或 NASH 及其相关症状和/或相关病理的方法，包括向有需要的受试者施用任何式 I 化合物及其药用和食品级可接受的盐，或包含相同成分的任何药物组合物、功能性食品添加剂或营养保健品组合物。
• Synthesis,<i>in vitro</i>Antiproliferative and Anti-<i>Mycobacterium tuberculosis</i>Activities of Novel β-Carboline Derivatives
  作者：Flora M. F. Moreira、Julio Croda、Maria H. Sarragiotto、Mary A. Foglio、Ana L. T. G. Ruiz、João E. Carvalho、Anelise S. N. Formagio

  DOI：10.5935/0103-5053.20160062

  日期：——

  A series of beta-carboline derivatives with amino or guanidinium were synthesized and evaluated in vitro against anti-Mycobacterium tuberculosis and for antiproliferative activities against nine human cancer cell lines. The compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) beta-carboline (24.9 mu g mL(-1)) and 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) beta-carboline (26.9 mu g mL(-1)) were the most active against M. Tuberculosis (MTB). Compounds 1-(4-hydroxyphenyl)-3-carboxamide( ethylamine) beta-carboline and 1-(4-methoxyphenyl)-3-carboxamide(propylamine) beta-carboline, which had the same substituted groups, inhibited the growth of all human tumor cell lines with growth inhibitory activity (GI(50)) values from 1.37 to 9.20 mmol L-1. Also in this series, compounds 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) beta-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) beta-carboline demonstrated significant activity against NCI/ADR cells. Among compounds with a terminal guanidine group, compounds 1-(4-hydroxyphenyl)-3carboxamide(ethyl) guanidine beta-carboline (27.8 mu g mL(-1)) and 1-(3-nitrophenyl)-3-carboxamide(ethyl) guanidine beta-carboline (37.4 mu g mL(-1)) demonstrated the greatest activity against MTB. Additionally, compounds 1-(4-methoxyphenyl)-3-carboxamide(ethyl) guanidine beta-carboline (GI(50) = 0.45 mmol L-1) effectively inhibited growth and was highly selective against NCI/ADR. The in silico study revealed that 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) beta-carboline, 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) beta-carboline, 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) beta-carboline, 1-(4-methoxyphenyl)-3-carboxamide(propylamine) beta-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) beta-carboline compounds follow the rules established by Lipinski, suggesting that this compound has no problems with oral bioavailability.