7-((4-benzylpiperidin-1-yl)methyl)-2,3,4,4a-tetrahydro-3,4,8,10-tetrahydroxy-2-(hydroxymethyl)-9-methoxypyrano[3,2-c]-isochromen-6(10bH)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 7-((4-benzylpiperidin-1-yl)methyl)-2,3,4,4a-tetrahydro-3,4,8,10-tetrahydroxy-2-(hydroxymethyl)-9-methoxypyrano[3,2-c]-isochromen-6(10bH)-one
• 英文别名: (2R,3S,4S,4aR,10bS)-7-[(4-benzylpiperidin-1-yl)methyl]-3,4,8,10-tetrahydroxy-2-(hydroxymethyl)-9-methoxy-3,4,4a,10b-tetrahydro-2H-pyrano[3,2-c]isochromen-6-one
• 化学式: C₂₇H₃₃NO₉
• 分子量: 515.56
• InChiKey: CWRHIBCQSUKTCK-AFOYLGMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  149
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 4-苄基哌啶 、 岩白菜素 以 二甲基亚砜 为溶剂， 反应 8.0h， 生成 7-((4-benzylpiperidin-1-yl)methyl)-2,3,4,4a-tetrahydro-3,4,8,10-tetrahydroxy-2-(hydroxymethyl)-9-methoxypyrano[3,2-c]-isochromen-6(10bH)-one
  参考文献：
  名称：

  Pyrano-isochromanones as IL-6 Inhibitors: Synthesis, in Vitro and in Vivo Antiarthritic Activity

  摘要：

  Bergenin (1), a unique fused C-glycoside isolated from Bergenia species, possesses interesting anti-inflammatory and antipain activities. To study SAR of this scaffold, first-generation derivatives were synthesized and evaluated for inhibition of lymphocyte proliferation and production of pro-inflammatory cytokines. The C-7 substituted derivatives showed inhibition of IL-6 as well as TNF-α production. Bergenin and its most potent IL-6 inhibitor derivatives 4e and 4f were then investigated in a panel of in vitro and in vivo inflammation/arthritis models. These compounds significantly decreased the expression of NF-kB and IKK-β in THP-1 cells. In in vivo study in BALB/c mice, a dose-dependent inhibition of SRBC-induced cytokines, reduction in humoral/cell-mediated immunity, and antibody titer was observed. The CIA study in DBA/1J mice indicated that compounds led to reduction in swelling of paws, cytokine levels, and anticollagen IgG1/IgG2a levels. The significant in vivo immunosuppressive efficacy of pyrano-isochromanones demonstrates the promise of this scaffold for development of next-generation antiarthritic drugs.

  DOI：

  10.1021/jm500901e

文献信息

• Pyrano-isochromanones as IL-6 Inhibitors: Synthesis, in Vitro and in Vivo Antiarthritic Activity
  作者：Shreyans K. Jain、Surjeet Singh、Anamika Khajuria、Santosh K. Guru、Prashant Joshi、Samdarshi Meena、Janhavi R. Nadkarni、Amarinder Singh、Sonali S. Bharate、Shashi Bhushan、Sandip B. Bharate、Ram A. Vishwakarma

  DOI：10.1021/jm500901e

  日期：2014.8.28

  Bergenin (1), a unique fused C-glycoside isolated from Bergenia species, possesses interesting anti-inflammatory and antipain activities. To study SAR of this scaffold, first-generation derivatives were synthesized and evaluated for inhibition of lymphocyte proliferation and production of pro-inflammatory cytokines. The C-7 substituted derivatives showed inhibition of IL-6 as well as TNF-α production. Bergenin and its most potent IL-6 inhibitor derivatives 4e and 4f were then investigated in a panel of in vitro and in vivo inflammation/arthritis models. These compounds significantly decreased the expression of NF-kB and IKK-β in THP-1 cells. In in vivo study in BALB/c mice, a dose-dependent inhibition of SRBC-induced cytokines, reduction in humoral/cell-mediated immunity, and antibody titer was observed. The CIA study in DBA/1J mice indicated that compounds led to reduction in swelling of paws, cytokine levels, and anticollagen IgG1/IgG2a levels. The significant in vivo immunosuppressive efficacy of pyrano-isochromanones demonstrates the promise of this scaffold for development of next-generation antiarthritic drugs.