4-((1R,3aR,10aR,13aS)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl)butyric acid | 1345731-45-4

• 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
• 英文名称: 4-((1R,3aR,10aR,13aS)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl)butyric acid
• 英文别名: sophoridinic acid
• CAS: 1345731-45-4
• 化学式: C₁₅H₂₆N₂O₂
• 分子量: 266.384
• InChiKey: AZXHMEMRJYOODA-BHPKHCPMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  52.57
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-((1R,3aR,10aR,13aS)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl)butyric acid 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 生成 12-N-(p-chlorobenzyl)sophoridinol
  参考文献：
  名称：

  12N取代的槐定胺作为新型抗癌剂的合成，生物学评估和自噬机理。

  摘要：

  合成了一系列12N-取代的槐定胺衍生物，并评估了它们在人HepG2肝癌细胞中的细胞毒活性。构效关系表明，在N'端引入合适的亚芳基或芳基乙基可以大大增强抗扩散能力。其中，具有N'-三甲氧基苯基亚甲基的化合物6b对包括HepG2，白血病（K562）和乳腺癌（HMLE）在内的三种人类肿瘤细胞系表现出有效的抗增殖作用，IC50在0.55至1.7μM之间。6b对抗肿瘤细胞的潜在机制是主要通过中和溶酶体酸性来阻断自噬通量。我们的结果表明，化合物6b是有效的溶酶体脱酸剂，因此能够阻断自噬通量并抑制肿瘤细胞的生长。

  DOI：

  10.1021/acsmedchemlett.6b00466
• 作为产物：
  描述：

  苦参碱 在 水 、 potassium hydroxide 作用下， 反应 10.0h， 以88%的产率得到4-((1R,3aR,10aR,13aS)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl)butyric acid
  参考文献：
  名称：

  多靶点抗肿瘤活性喹诺里西啶类衍生物及其制备方法与应用

  摘要：

  本发明属于医药技术领域，提供了一种基于拓扑异构酶（Top1）和组蛋白去乙酰化酶（HDAC）多靶点的喹诺里西啶类衍生物，具有通式（Ⅰ）所示的结构，以及其光学异构体，非对映异构体和消旋体混合物，其药学上可接受的盐。本发明进一步公开了喹诺里西啶类衍生物及其药学上可接受盐在治疗基因表达异常而引起疾病药物中的应用，主要包括用于治疗恶性肿瘤及与分化增殖相关疾病。实验结果显示：喹诺里西啶类衍生物的7b和7e均表现出优秀的体内抑制活性，体内抑瘤率分别为65.59%和78.49%，并具有克服肿瘤耐药性的潜力，有进一步研究的价值。

  公开号：

  CN111747957B

文献信息

• Novel Sophoridine Derivatives Bearing Phosphoramide Mustard Moiety Exhibit Potent Antitumor Activities In Vitro and In Vivo
  作者：Dongdong Li、Linlin Dai、Xiumei Zhao、Shuang Zhi、Hongsheng Shen、Zibo Yang

  DOI：10.3390/molecules23081960

  日期：——

  Novel mustard functionalized sophoridine derivatives were synthesized and evaluated for their cytotoxicity against of a panel of various cancer cell lines. They were shown to be more sensitive to S180 and H22 tumor cells with IC50 values ranging from 1.01⁻3.65 μM, and distinctly were more cytotoxic to cancer cells than normal cell L929. In addition, compounds 7a, 7c, and 7e displayed moderate tumor

  合成了新型芥末功能化的槐定碱衍生物，并评估了它们对多种癌细胞系的细胞毒性。它们显示出对S180和H22肿瘤细胞更敏感，IC50值在1.01⁻3.65μM之间，并且比正常细胞L929对癌细胞具有更强的细胞毒性。另外，化合物7a，7c和7e显示出中等程度的肿瘤抑制作用，而对荷有H22肝肿瘤的小鼠在体内没有明显的器官毒性。此外，他们将肿瘤细胞阻滞在G1期并诱导细胞凋亡。还研究了它们与DNA-Top I复合物的潜在结合方式。
• Synthesis and Antitumor Effect of Sophoridine Derivatives Bearing an Acyclic Aryloxy Phosphoramidate Mustard Functionality
  作者：Lin-Lin Dai、Dong-Dong Li、Xiu-Mei Zhao、Shuang Zhi、Hong-Sheng Shen、Zi-Bo Yang

  DOI：10.1002/jhet.3413

  日期：2019.2

  series of acyclic aryloxy phosphoramidate mustard functionalized sophoridine derivatives were synthesized and screened for cytostatic activity in a range of different tumor cell lines (S180, H22, K562, MCF‐7, SMMC‐7721, and LoVo). All these compounds were shown to be more sensitive to S180 and H22 cells with IC50 values ranging from 2.10 to 7.21 μM. In addition, all targeted derivatives distinctly

  为了提高槐定碱的效力，将氨基磷酸酯芥子基序掺入D环打开的槐定碱支架中。合成了一系列无环芳氧基氨基磷酰胺芥末官能化的槐定碱衍生物，并针对一系列不同的肿瘤细胞系（S180，H22，K562，MCF-7，SMMC-7721和LoVo）筛选了细胞抑制活性。被证明是对S180和H22细胞与IC更敏感所有这些化合物50个值范围从2.10到7.21μ中号。另外，所有靶向衍生物显然比正常细胞L929对癌细胞具有更高的细胞毒性。化合物8b，8c，8d和8e表现出中等程度的肿瘤抑制作用，没有明显的器官毒性在体内针对患有H22肝肿瘤的小鼠。还研究了它们与DNA拓扑异构酶I复合物的潜在结合方式。
• Sophoridine Derivatives Induce Apoptosis and Autophagy to Suppress the Growth of Triple‐Negative Breast Cancer through Inhibition of mTOR Signaling
  作者：Linlin Dai、Luyao Wang、Cheng Tan、Jun Cai、Hongsheng Shen、Ting Zhang、Shuang Zhi、Zibo Yang、Yunhui Hu、Xiumei Zhao、Dongdong Li

  DOI：10.1002/cmdc.202100434

  日期：2022.1.5

  and therapeutic margins of the natural product sophoridine, novel nitrogen mustard carbamate derivatives were synthesized. We found all the tested compounds to be more potent against the triple-negative breast cancer cell line MDA-MB-231. Altogether, our work describes new leads to yield more potent chemotherapeutics against triple-negative breast cancers, possibly mesenchymal stem-like subtype.

  为了提高天然产物槐定碱的抗肿瘤效力和治疗范围，合成了新型氮芥氨基甲酸酯衍生物。我们发现所有测试的化合物都对三阴性乳腺癌细胞系 MDA-MB-231 更有效。总而言之，我们的工作描述了产生针对三阴性乳腺癌（可能是间充质干细胞样亚型）的更有效化学疗法的新线索。
• Synthesis, structure–activity relationship and biological evaluation of anticancer activity for novel N-substituted sophoridinic acid derivatives
  作者：Xin Li、Wu-Li Zhao、Jian-Dong Jiang、Kai-Huan Ren、Na-Na Du、Yang-Biao Li、Yan-Xiang Wang、Chong-Wen Bi、Rong-Guang Shao、Dan-Qing Song

  DOI：10.1016/j.bmcl.2011.07.038

  日期：2011.9

  been used in China for decades. A series of novel N-substituted sophoridinic acid derivatives were synthesized and evaluated for their cytotoxicity with 1 as the lead. The structure–activity relationship indicated that introduction of an aliphatic acyl on the nitrogen atom might significantly enhance the anticancer activity. Among the compounds, 6b bearing bromoacetyl side-chain afforded a potential

  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。
• 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.