2,3-methenedioxy-9-heptanoyloxy-10-methoxyprotoberberine chloride | 1252119-08-6

• 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-methenedioxy-9-heptanoyloxy-10-methoxyprotoberberine chloride
• 英文别名: (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) heptanoate;chloride
• CAS: 1252119-08-6
• 化学式: C₂₆H₂₈NO₅*Cl
• 分子量: 469.965
• InChiKey: PFIHQUBXZJERTM-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.97
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  小檗红碱 、 庚酰氯 在 吡啶 作用下， 以 乙腈 为溶剂， 生成 2,3-methenedioxy-9-heptanoyloxy-10-methoxyprotoberberine chloride
  参考文献：
  名称：

  Design, synthesis, and cholesterol-lowering efficacy for prodrugs of berberrubine

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2010.06.106

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.