N-α-Methyl-tetrahydropseudoberberin | 1100757-83-2

• 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: N-α-Methyl-tetrahydropseudoberberin
• 英文别名: N-β-Methyl-tetrahydropseudoberberin；10,11-dimethoxy-7ξ-methyl-(13ar)-5,8,13,13a-tetrahydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolinium; iodide；10,11-dimethoxy-7-methyl-2,3-methylenedioxy-berbinium; iodide；10,11-Dimethoxy-7-methyl-2,3-methylendioxy-berbinium; Jodid；17,18-Dimethoxy-13-methyl-5,7-dioxa-13-azoniapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-2,4(8),9,15,17,19-hexaene;iodide
• CAS: 1100757-83-2
• 化学式: C₂₁H₂₄NO₄*I
• 分子量: 481.33
• InChiKey: NCKKNOLBCBHZFU-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.24
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  四氢假小檗碱 、 碘甲烷 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以40%的产率得到N-α-Methyl-tetrahydropseudoberberin
  参考文献：
  名称：

  Berberine Analogues as a Novel Class of the Low-Density-Lipoprotein Receptor Up-Regulators: Synthesis, Structure−Activity Relationships, and Cholesterol-Lowering Efficacy

  摘要：

  Twenty-nine derivatives of berberine (1) or pseudoberberine (2) were designed, semisynthesized, and evaluated for their up-regulatory activity on the low-density-lipoprotein receptor (LDLR) expression. SAR analysis revealed that (i) the methylenedioxy group at the 2- and 3-position is an essential element to keep the activity, (ii) the 7-position quaternary ammonium and planar structure of the compound are activity-required, and (iii) addition of electron-donating groups at the 7- or 13-position reduced the activity. Of the compound I analogues, compound 2 exhibited an increased activity on LDLR expression compared to 1. In the hyperlipidemic rats, compound 2 (100 (mg/kg)/day) reduced blood CHO and LDL-c by 42.6% and 49.4%, respectively, more efficient than I did (p < 0.01 for both). The results were confirmed in the hyperlipidemic mice. LD50 of 2 in mice was over 5000 mg/kg (oral). We consider compound 2 a promising cholesterol-lowering drug candidate.

  DOI：

  10.1021/jm801157z

文献信息

• Haworth; Perkin; Rankin, Journal of the Chemical Society, 1924, vol. 125, p. 1700
  作者：Haworth、Perkin、Rankin

  DOI：——

  日期：——
• Berberine Analogues as a Novel Class of the Low-Density-Lipoprotein Receptor Up-Regulators: Synthesis, Structure−Activity Relationships, and Cholesterol-Lowering Efficacy
  作者：Ying-Hong Li、Peng Yang、Wei-Jia Kong、Yan-Xiang Wang、Chang-Qin Hu、Zeng-Yan Zuo、Yue-Ming Wang、Hong Gao、Li-Mei Gao、Yan-Chun Feng、Na-Na Du、Ying Liu、Dan-Qing Song、Jian-Dong Jiang

  DOI：10.1021/jm801157z

  日期：2009.1.22

  Twenty-nine derivatives of berberine (1) or pseudoberberine (2) were designed, semisynthesized, and evaluated for their up-regulatory activity on the low-density-lipoprotein receptor (LDLR) expression. SAR analysis revealed that (i) the methylenedioxy group at the 2- and 3-position is an essential element to keep the activity, (ii) the 7-position quaternary ammonium and planar structure of the compound are activity-required, and (iii) addition of electron-donating groups at the 7- or 13-position reduced the activity. Of the compound I analogues, compound 2 exhibited an increased activity on LDLR expression compared to 1. In the hyperlipidemic rats, compound 2 (100 (mg/kg)/day) reduced blood CHO and LDL-c by 42.6% and 49.4%, respectively, more efficient than I did (p < 0.01 for both). The results were confirmed in the hyperlipidemic mice. LD50 of 2 in mice was over 5000 mg/kg (oral). We consider compound 2 a promising cholesterol-lowering drug candidate.