2,3-methylenedioxy-9-ethyloxyformyloxy-10-methoxyprotoberberine chloride

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 英文名称: 2,3-methylenedioxy-9-ethyloxyformyloxy-10-methoxyprotoberberine chloride
• 英文别名: 2,3-methenedioxy-9-ethyloxyformyl-10-methoxyprotoberberine chloride；Ethyl (17-methoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-1(13),2,4(8),9,14,16,18,20-octaen-16-yl) carbonate;chloride
• 化学式: C₂₂H₂₀NO₆*Cl
• 分子量: 429.857
• InChiKey: VGNQWWMCCLNIIO-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.63
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  67.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  盐酸小檗碱 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 70.0 ℃ 、5.33 kPa 条件下， 反应 1.0h， 生成 2,3-methylenedioxy-9-ethyloxyformyloxy-10-methoxyprotoberberine chloride
  参考文献：
  名称：

  通过MEK / ERK途径和自噬，小ber碱衍生物作为抗肠道病毒的新型抗病毒剂，其合成与演化。

  摘要：

  以小ber碱（BBR）为首，合成了23种新的BBR衍生物，并通过细胞病变效应（CPE）分析检测了它们对四种不同基因型肠病毒71（EV71）菌株的抗病毒活性。结构-活性关系（SAR）研究表明，在9位上引入合适的取代基可能对效能有所帮助。其中，化合物2d表现出最强的活性，IC50值为7.12⁻14.8μM，与BBR相似。RNA和蛋白质水平均以剂量依赖性方式进一步证实了2d的作用。该机制表明2d可以抑制MEK / ERK信号通路的激活。同时，它可以通过激活AKT并抑制JNK和PI3KIII蛋白的磷酸化来抑制EV71诱导的自噬。

  DOI：

  10.3390/molecules23082084

文献信息

• 13,13A-DIHYDROBERBERINE DERIVATIVES, THEIR PHARMACEUTICAL COMPOSITION AND USE
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：EP2070926B1

  公开（公告）日：2011-09-07
• Design, synthesis, and cholesterol-lowering efficacy for prodrugs of berberrubine
  作者：Ying-Hong Li、Yi Li、Peng Yang、Wei-Jia Kong、Xue-Fu You、Gang Ren、Hong-Bin Deng、Yue-Ming Wang、Yan-Xiang Wang、Jian-Dong Jiang、Dan-Qing Song

  DOI：10.1016/j.bmc.2010.06.106

  日期：2010.9

  In order to enhance oral bioavailability of berberine (BBR) for its cholesterol-lowering efficacy in vivo, a series of ester or ether prodrugs of berberrubine (M1), which is an active metabolite of BBR after first-pass metabolism, were designed, semi-synthesized, and evaluated. Among these M1 prodrugs, compound 5g possessing palmitate at the 9-position showed a moderate Log P value and esterase hydrolysis rate for releasing M1 in blood. Its cholesterol-lowering efficacy in vivo was evaluated in hyperlipidemic SD rats. Compound 5g (100 mg/kg/d) reduced blood CHO and LDL-c by 35.8% and 45.5%, respectively, similar to that by BBR. It also exhibited a good safety in rats with no side-effect on liver and kidney function. Therefore, the design of M1 prodrug appears to be an effective strategy to improve pharmacokinetic feature of BBR for its lipid-lowering efficacy in vivo. (C) 2010 Elsevier Ltd. All rights reserved.
• Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity
  作者：Kinuko Iwasa、Yumi Nishiyama、Momoyo Ichimaru、Masataka Moriyasu、Hye-Sook Kim、Yusuke Wataya、Takao Yamori、Turuo Takashi、Dong-Ung Lee

  DOI：10.1016/s0223-5234(99)00127-0

  日期：1999.12

  Seventeen quaternary protoberberine alkaloids related to berberine I were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the oxygen substituents on rings A, C and D and the position of the oxygen functions on ring D. The position of the oxygen functions on ring D and the type of the oxygen substituents at the C-13 position (ring C) strongly influenced the activity. Shifting the oxygen functions at C-9 and C-10 to C-10 and C-Il on ring D resulted in a significant increase in the activity. Compounds bearing a methylenedioxy function at C-2 and C-3 (ring A) or C-9 and C-IO (ring D) showed higher activity than those which have methoxy groups at the same positions. Introduction of a methoxy group into the C-l position (ring A) decreased the activity. Replacement of a hydroxy group at C-2 or C-3 (ring A) by a methoxy group led to a reduction in the activity. Displacement of a hydroxy function at C-13 (ring C) by the oxygen substituents such as OMe, Oft, OCOOEt, and OCON(Me)(2) reduced the activity. In the same replacement at C-9 (ring D), the activity depended upon the type of the oxygen function. Six protoberberines displayed more potent activity than berberine 1. The activity decreased in the order: 10, 11, 17 and 18 > 7 and 8 > 1. (C) 1999 Editions scientifiques et medicales Elsevier SAS.