(6aS,10S,11aR,11bR,11cS)-10-methylamino-dodecahydro-3a,7a-diazabenzo(de)anthracene-8-thione | 1261068-12-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (6aS,10S,11aR,11bR,11cS)-10-methylamino-dodecahydro-3a,7a-diazabenzo(de)anthracene-8-thione
• 英文别名: 13-(N-methyl)amino-15-thiomatrine；(1R,2R,4S,9S,17S)-4-(methylamino)-7,13-diazatetracyclo[7.7.1.02,7.013,17]heptadecane-6-thione
• CAS: 1261068-12-5
• 化学式: C₁₆H₂₇N₃S
• 分子量: 293.476
• InChiKey: FBGUEFOJHHACIV-JAAXMTQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  50.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6aS,10S,11aR,11bR,11cS)-10-methylamino-dodecahydro-3a,7a-diazabenzo(de)anthracene-8-thione 在 potassium carbonate 、 二乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.17h， 生成 13-[N-methyl-Ν-(2-allylaminoacetyl)] amino-15-thiomatrine
  参考文献：
  名称：

  一组苦参碱类化合物用于制备抗肝纤维化和抗 肝癌药物的应用

  摘要：

  本发明涉及化合物及其盐的应用，所述化合物及其盐是一组苦参碱类化合物及其盐用于制备抗肝纤维化和抗肝癌药物的应用。本发明优点在于：本发明的化合物能显著抑制肝癌细胞株Hep‑G2，Hun‑7,MHCC‑97L,SMMC‑7721和Hep‑3B的增殖以及成纤维细胞BJ,人肝星状细胞LX‑2,大鼠肝星状细胞HSC‑T6的增殖活性，可用于制备治疗抗肝纤维化和治疗抗肝癌的药物。

  公开号：

  CN103933038B
• 作为产物：
  描述：

  布雷菲德菌素A 在 劳森试剂 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 (6aS,10S,11aR,11bR,11cS)-10-methylamino-dodecahydro-3a,7a-diazabenzo(de)anthracene-8-thione
  参考文献：
  名称：

  一组苦参碱类化合物用于制备抗肝纤维化和抗 肝癌药物的应用

  摘要：

  本发明涉及化合物及其盐的应用，所述化合物及其盐是一组苦参碱类化合物及其盐用于制备抗肝纤维化和抗肝癌药物的应用。本发明优点在于：本发明的化合物能显著抑制肝癌细胞株Hep‑G2，Hun‑7,MHCC‑97L,SMMC‑7721和Hep‑3B的增殖以及成纤维细胞BJ,人肝星状细胞LX‑2,大鼠肝星状细胞HSC‑T6的增殖活性，可用于制备治疗抗肝纤维化和治疗抗肝癌的药物。

  公开号：

  CN103933038B

文献信息

• 一类苦参碱衍生物及其制备方法
  申请人：中国人民解放军第二军医大学

  公开号：CN103936736B

  公开（公告）日：2016-04-06

  本发明涉及一类苦参碱衍生物及其盐，具体涉及具有以下化学结构通式的一类新的苦参碱类化合物及其盐类：通式中X是硫原子；n选自取1,2；R1选自烷基，烷氧基，芳基，取代芳基；R2选自氢，烷基，取代烷基；本发明还提供了一类苦参碱衍生物及其盐制备方法。本发明制备方法产率高，化合物抗肿瘤效果好，且具靶向、低毒、等优点；本发明制备方法得到的目标分子的稳定性高。部分化合物的活性明显优于化合物M19。
• Development of novel bone targeting peptide–drug conjugate of 13-aminomethyl-15-thiomatrine for osteoporosis therapy
  作者：Jia Su、Chao Liu、Haohao Bai、Wei Cong、Hua Tang、Honggang Hu、Li Su、Shipeng He、Yong Wang

  DOI：10.1039/d1ra08136e

  日期：——

  group was a promising candidate for novel anti-osteoporosis drug development. However, the application of M19 was limited by its unsatisfactory druggability including poor chemical stability, excessively broad pharmacological activity and some degree of cytotoxicity. To solve these problems, M19-based bone targeting and cathepsin K sensitive peptide–drug conjugates (BTM19-1, BTM19-2 and BTM19-3) were

  我们研究组之前开发的13-Aminomethyl-15-thiomatrine ( M19 ) 是一种很有前途的新型抗骨质疏松药物开发候选者。然而，M19的应用受到其化学稳定性差、药理活性过宽和一定程度的细胞毒性等成药性不理想的限制。为了解决这些问题，开发了基于M19的骨靶向和组织蛋白酶 K 敏感肽-药物偶联物（BTM19-1、BTM19-2和BTM19-3），以实现药物在骨组织中的精确释放。随后的研究表明，通过组织蛋白酶 K 消化，但在糜蛋白酶中的几个小时内具有足够的稳定性。此外，还显示出显着提高的化学稳定性和强的羟基磷灰石结合亲和力。在生物学评估研究中，与原型药物相比，这些 PDC 显示出较少的细胞毒性和相似的破骨细胞抑制活性。最佳的BTM19-2可以作为进一步骨质疏松症治疗研究的合适候选者。
• Synthesis and in vitro inhibitory activity of matrine derivatives towards pro-inflammatory cytokines
  作者：Honggang Hu、Shaozhan Wang、Chunmei Zhang、Liang Wang、Li Ding、Junping Zhang、Qiuye Wu

  DOI：10.1016/j.bmcl.2010.09.075

  日期：2010.12

  Matrine, a sophora alkaloid, exhibited good anti-inflammation effects in our previous report. In the present study, a series of matrine derivatives were synthesized via classical Michael addition. Biological studies showed that the synthetic derivatives had good inhibitory effect towards TNF-alpha production and NF kappa B transcriptional activity. The introduction of various amino groups to the keto beta position could improve the biochemical profile, resulting in the identification of more potent derivates, such as 1f, with higher inhibitory activity than both matrine and sophoramine. (C) 2010 Published by Elsevier Ltd.
• Survivin-targeted drug screening platform identifies a matrine derivative WM-127 as a potential therapeutics against hepatocellular carcinoma
  作者：Haisen Yin、Risheng Que、Chunying Liu、Weidan Ji、Bin Sun、Xuejing Lin、Qin Zhang、Xinying Zhao、Zhangxiao Peng、Xiaofeng Zhang、Haihua Qian、Lei Chen、Yonggang Yao、Changqing Su

  DOI：10.1016/j.canlet.2018.03.044

  日期：2018.7

  Hepatocellular carcinoma (HCC) is the second leading cause of cancer related death which needs novel drugs to improve patient outcome. Survivin overexpresses in HCC and contributes to HCC malignant progression. In this study, we established a Survivin-targeted drug screening platform, a cell model HepG2-Sur5P-EGFP-Sur3U stably transfected with lentivirus carrying an EGFP expression cassette, in which the EGFP expression was regulated by the upstream Survivin promoter and downstream Survivin 3'-UTR By using this platform, we screened and easily identified one of matrine derivatives, WM-127, from hundreds of matrine derivatives. WM-127 was demonstrated to be a strong Survivin inhibitor that inhibited cell proliferation, induced cell cycle arrest and apoptosis of HCC cells, and suppressed the growth of HCC xenografted tumors in nude mice, suggesting that WM-127 might be a promising drug for HCC treatment. WM-127 exhibited less cytotoxicity in normal cells. Mechanistic studies showed that WM-127 suppressed the activity of Survivinal/beta-catenin pathway and the expression of Bax to induce cell cycle arrest and apoptosis. Taken together, we constructed an economical, practical, efficient and convenient cell platform for screening the Survivin-targeted drugs from the enormous diversity of chemicals or factors, which would be a potential tool for antitumor drug research and development. (C) 2018 Elsevier B.V. All rights reserved.