4-((1R,3aR,3a1S,10aS)-2-tosyldecahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl)butanoic acid | 1345731-32-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((1R,3aR,3a1S,10aS)-2-tosyldecahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl)butanoic acid
• CAS: 1345731-32-9
• 化学式: C₂₂H₃₂N₂O₄S
• 分子量: 420.573
• InChiKey: DDKQWRLMFGVGME-RQGSJKACSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.11
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  77.92
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  槐定碱 在 potassium carbonate 、 间甲酚 、 potassium hydroxide 作用下， 以 二氯甲烷 、 Petroleum ether 为溶剂， 反应 58.0h， 生成 4-((1R,3aR,3a1S,10aS)-2-tosyldecahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl)butanoic acid
  参考文献：
  名称：

  N-取代的槐定酸衍生物的合成，构效关系及抗癌活性的生物学评价

  摘要：

  天然的抗癌药物槐定碱（1）在中国已经使用了数十年。合成了一系列新颖的N-取代的槐定酸衍生物，并以1为先导对其细胞毒性进行了评估。结构-活性关系表明，在氮原子上引入脂族酰基可能会显着增强抗癌活性。在这些化合物中，带有溴乙酰基侧链的6b对四种人类肿瘤细胞系（肝，结肠，乳腺和肺）具有潜在的作用。6b的作用机制是抑制DNA拓扑异构酶I的活性，随后S期停滞，然后导致凋亡性细胞死亡，类似于其亲本1。我们认为6b有希望用于进一步的抗癌研究。

  DOI：

  10.1016/j.bmcl.2011.07.038

文献信息

• Structure–activity relationship and hypoglycemic activity of tricyclic matrines with advantage of treating diabetic nephropathy
  作者：Sheng Tang、Can Wang、Ying–Hong Li、Tian–Yu Niu、Yuan–Hui Zhang、Yu–Dong Pang、Yan–Xiang Wang、Wei–Jia Kong、Dan–Qing Song

  DOI：10.1016/j.ejmech.2020.112315

  日期：2020.9

  Forty-three tricyclic matrinic derivatives with a unique scaffold were prepared and evaluated for their stimulation effects on glucose consumption in HepG2 cells. The structure-activity relationship was systematically elucidated for the first time. Among them, compound 17a exhibited the most promising potency, and dose-dependently increased glucose consumption in L6 myotubes. It significantly lowered blood glucose, glucosylated haemoglobin and AGE level, and improved glucose tolerance and insulin resistance in KK-Ay mice as well. More importantly, 17a effectively ameliorated diabetic nephropathy (DN), as indicated by the improvement of renal function and pathological changes, and decrease of urinary protein. Furthermore, 17a could induce glycolysis but suppressed aerobic oxidation of glucose, in a similar mechanism to Metform. Our results indicated that in addition to hyperglycemia, 17a may be developed to treat diabetic complication such as DN. (C) 2020 Elsevier Masson SAS. All rights reserved.