9-Pivaloyl, 9-demethylberberine chloride | 59895-70-4

• 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: 9-Pivaloyl, 9-demethylberberine chloride
• 英文别名: 2,3-methylenedioxy-9-pivaloyloxy-10-methoxyprotoberberine chloride；2,3-methenedioxy-9-pivaloyloxy-10-methoxyprotoberberine chloride；(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) 2,2-dimethylpropanoate;chloride
• CAS: 59895-70-4
• 化学式: C₂₄H₂₄NO₅*Cl
• 分子量: 441.911
• InChiKey: VITYBPYOKBUAPI-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.04
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  盐酸小檗碱 在 三乙胺 作用下， 以 乙腈 为溶剂， 70.0~210.0 ℃ 、5.33 kPa 条件下， 生成 9-Pivaloyl, 9-demethylberberine chloride
  参考文献：
  名称：

  新型小Ber碱衍生物作为抗TNF-α诱导的NF-κB活化的强抑制剂的合成与鉴定。

  摘要：

  合成了在环D的取代基上定义的二十三种新的小碱（BBR）类似物，并评估了其抑制肿瘤坏死因子（TNF）-α诱导的核因子（NF）-κB活化的活性。结构-活性关系（SAR）分析表明，在9位上合适的叔/季碳取代基或10位上的刚性片段可能有利于增强其抗炎能力。其中，化合物2d，2e，2i和2j对NF-κB活化表现出令人满意的抑制作用，抑制率约为90％（5μM），远优于BBR。初步的机制研究表明，它们均可以通过削弱IκB激酶（IKK）磷酸化以及TNF-α诱导的细胞因子白介素（IL）-6和IL-8来抑制TNF-α诱导的NF-κB活化。所以，

  DOI：

  10.3390/molecules22081257

文献信息

• 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.
• Synthesis and Identification of Novel Berberine Derivatives as Potent Inhibitors against TNF-α-Induced NF-κB Activation
  作者：Yan-Xiang Wang、Lu Liu、Qing-Xuan Zeng、Tian-Yun Fan、Jian-Dong Jiang、Hong-Bin Deng、Dan-Qing Song

  DOI：10.3390/molecules22081257

  日期：——

  A preliminary mechanism study revealed that all of them could inhibit TNF-α-induced NF-κB activation via impairing IκB kinase (IKK) phosphorylation as well as cytokines interleukin (IL)-6 and IL-8 induced by TNF-α. Therefore, the results provided powerful information on further structural modifications and development of BBR derivatives into a new class of anti-inflammatory candidates for the treatment

  合成了在环D的取代基上定义的二十三种新的小碱（BBR）类似物，并评估了其抑制肿瘤坏死因子（TNF）-α诱导的核因子（NF）-κB活化的活性。结构-活性关系（SAR）分析表明，在9位上合适的叔/季碳取代基或10位上的刚性片段可能有利于增强其抗炎能力。其中，化合物2d，2e，2i和2j对NF-κB活化表现出令人满意的抑制作用，抑制率约为90％（5μM），远优于BBR。初步的机制研究表明，它们均可以通过削弱IκB激酶（IKK）磷酸化以及TNF-α诱导的细胞因子白介素（IL）-6和IL-8来抑制TNF-α诱导的NF-κB活化。所以，