N-p-tosylmatrinic acid | 1331769-87-9

• 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: N-p-tosylmatrinic acid
• 英文别名: 12-N-p-ethylbenzenesulfonyl matrinic acid；DM-102；4-[(5S,6R,9S,13S)-7-(4-methylphenyl)sulfonyl-1,7-diazatricyclo[7.3.1.05,13]tridecan-6-yl]butanoic acid
• CAS: 1331769-87-9
• 化学式: C₂₂H₃₂N₂O₄S
• 分子量: 420.573
• InChiKey: DDKQWRLMFGVGME-RYTRXMBJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-p-tosylmatrinic acid 在 氯化亚砜 作用下， 反应 1.0h， 生成
  参考文献：
  名称：

  Construction and synthesis of tricyclic matrinic derivatives against influenza A virus by privileged structure strategy

  摘要：

  设计、合成并评估了一系列具有11-阿曼丹基团的新型马曲宁衍生物，以其抗甲型流感A H3N2活性为基础，采用了优选结构策略。SAR分析表明，通过酯链引入11-阿曼丹基团可能有助于提高活性。在这些化合物中，7b显示出良好的抗H3N2活性，IC50值为5.14 μM，略优于阿曼达啂。其活性在蛋白水平上得到了进一步验证。在初步机制中，化合物7b能够通过靶向M2蛋白抑制病毒复制周期的早期阶段，这与阿曼达啂的作用机制一致。本研究代表了优选阿曼达啂片段结合策略在进一步结构优化和开发新型抗流感药物方面的成功应用。

  DOI：

  10.1691/ph.2019.8968
• 作为产物：
  描述：

  苦参碱 在 盐酸 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 9.0h， 生成 N-p-tosylmatrinic acid
  参考文献：
  名称：

  作为杀虫/杀螨剂的松香/草胺酰胺衍生物的制备及其对朱砂叶螨的作用机理研究

  摘要：

  在继续开发基于天然产物的杀虫候选物的计划中，通过苦参碱的结构优化获得了苦参碱/氧化苦参胺。N '-（4-氟）苯基-N-（4-溴）苯基磺酰氧基rin酰胺（IIm）对分离的Mythimna separata具有较强的杀虫活性。N-（Un）取代的苯磺酰matrinic酸（3a – c）表现出有希望的杀螨活性对朱砂叶螨（Tetranychus cinnabarinus）。通过qRT-PCR分析nAChR亚基和AChE基因并确定（未处理）朱砂丁香的AChE活性，这表明与α2，α4，α5和β3nAChR亚基作用时，苦参碱和羧基的内酰胺开环和N-（4-甲基）苯基磺酰基matrinic acid（3b）的（4-甲基）苯基磺酰基是必需的；化合物3b是朱砂中乙酰胆碱酯酶（AChE）的抑制剂，而乙酰胆碱酯酶（AChE）是朱砂中对抗3b的可能作用靶之一; 化合物3b可能是朱砂纲中nAChR和AChE的拮抗剂。

  DOI：

  10.1021/acs.jafc.9b05092

文献信息

• Discovery of Matrinic Thiadiazole Derivatives as a Novel Family of Anti-Liver Fibrosis Agents via Repression of the TGFβ/Smad Pathway
  作者：Tianyu Niu、Weixiao Niu、Yunyang Bao、Ting Liu、Danqing Song、Yinghong Li、Hongwei He

  DOI：10.3390/molecules23071644

  日期：——

  A series of novel matrinic thiadiazole derivatives were designed, synthesized and evaluated for their inhibitory effect on COL1A1 promotor. The SAR indicated that: (i) the introduction of a thiadiazole on the 11-side chain was beneficial for activity; (ii) a 12-N-benzyl moiety was favorable for activity. Among them, compound 6n displayed a high activity with an inhibitory rate of 39.7% at a concentration of 40 μM. It also effectively inhibited the expression of two representative collagen proteins (COL1A1 and α-SMA) on both the mRNA and protein levels and showed a high safety profile in vivo, indicating its great promise as an anti-liver fibrosis agent. Further study indicated that it might repress hepatic fibrogenesis via the TGFβ/Smad pathway. This study provided powerful information for further strategic optimization and the top compound 6n was selected for further study as an ideal liver fibrosis lead for next investigation.

  设计、合成并评估了一系列新型母体噻二唑衍生物对COL1A1启动子的抑制作用。结构活性关系表明：(i) 在11位侧链上引入噻二唑有利于活性；(ii) 12-N-苄基部分有利于活性。其中，化合物6n表现出高活性，在40 μM浓度下抑制率为39.7%。它还能有效抑制两种代表性胶原蛋白(COL1A1和α-SMA)在mRNA和蛋白质水平的表达，并在体内显示出高安全性，表明其在抗肝纤维化药物方面具有巨大潜力。进一步研究显示，它可能通过TGFβ/Smad途径抑制肝纤维化。这项研究为进一步战略优化提供了有力信息，选择化合物6n作为理想的肝纤维化先导物进行进一步研究。
• Evaluation of biological activities, and exploration on mechanism of action of matrine–cholesterol derivatives
  作者：Jianwei Xu、Zhiqiang Sun、Meng Hao、Min Lv、Hui Xu

  DOI：10.1016/j.bioorg.2019.103439

  日期：2020.1

  products matrine and cholesterol. Two N-phenylsulfonylmatrinic esters (5i and 5j) showed the most potent insecticidal activity against Mythimna separata Walker. Two N-benzylmatrinic esters (5e and 5g) exhibited the most promising aphicidal activity against Aphis citricola Van der Goot. Especially compound 5e showed good control effects in the greenhouse against A. citricola. Some interesting results

  为了开发新的潜在农药，通过对两种非食品生物活性产物苦参碱和胆固醇进行改性，制备了一系列苦参碱-胆固醇衍生物。两种N-苯基磺酰基matrinic酯（5i和5j）对Mythimna separata Walker的杀虫活性最强。两种N-苄基matrinic酯（5e和5g）对柠檬蚜Avans citricola Van der Goot表现出最有希望的杀蚜虫活性。尤其是化合物5e在温室中显示了对柠檬曲霉的良好控制效果。他们的结构-活性关系的一些有趣的结果也被观察到。通过逆转录聚合酶链反应（RT-PCR）和定量实时聚合酶链反应（qRT-PCR）分析柠檬酸曲霉成人的HMG-CoA还原酶，
• 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.
• EP2581376
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis, structure−activity relationship and biological evaluation of novel N-substituted matrinic acid derivatives as host heat-stress cognate 70 (Hsc70) down-regulators
  作者：Na-Na Du、Xin Li、Yu-Ping Wang、Fei Liu、Yan-Xin Liu、Chun-Xin Li、Zong-Gen Peng、Li-Mei Gao、Jian-Dong Jiang、Dan-Qing Song

  DOI：10.1016/j.bmcl.2011.06.071

  日期：2011.8

  Oxymatrine (1) is a natural anti-hepatitis B virus (HBV) drug that down-regulates host heat-stress cognate 70 (Hsc70) expression through a mechanism different from that of nucleosides. Taking Hsc70 as a target against HBV, 26 novel N-substituted matrinic acid analogs were designed, synthesized and evaluated for their regulation of Hsc70 mRNA expression with 1 as the lead. The SAR analysis revealed that (i) the carboxyl group at the 11-position was required for activity; (ii) introducing of a substituent on the nitrogen atom at the 12-position of 3, especially substituted benzyl, might significantly improve the activity. Among these analogs, compound 9p possessing N-p-methoxylbenzyl afforded an increased anti-HBV effect in comparison with 1. We consider 9p a promising anti-HBV candidate. (C) 2011 Elsevier Ltd. All rights reserved.