7-((diethylamino)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 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 7-((diethylamino)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-(diethylaminomethyl)-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: C₁₉H₂₇NO₉
• 分子量: 413.425
• InChiKey: UAFRKQOASLZXGM-HBPTYVBASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 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 、 岩白菜素 、 二乙胺 以 水 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 7-((diethylamino)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：

  [EN] TETRAHYDRO-2H-PYRANO[3,2-C]ISOCHROMENE-6-ONES AND ANALOGS FOR THE TREATMENT OF INFLAMMATORY DISORDERS
  [FR] TÉTRAHYDRO-2H-PYRANO[3,2-C]ISOCHROMÈNE-6-ONES ET ANALOGUES POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES

  摘要：

  本发明涉及式I中的2,3,4,4a-四氢-3,4,8,10-四羟基-2-(羟甲基)-9-甲氧基吡喃[3,2-c]异色素-6(10bH)-酮类似物，其中，R、R'和R"如本文所述。此外，本发明涉及使用化合物治疗或预防各种炎症性疾病，如类风湿性关节炎、炎症性肠病、银屑病、哮喘和慢性阻塞性肺疾病的方法。

  公开号：

  WO2014188440A1

文献信息

• [EN] TETRAHYDRO-2H-PYRANO[3,2-C]ISOCHROMENE-6-ONES AND ANALOGS FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] TÉTRAHYDRO-2H-PYRANO[3,2-C]ISOCHROMÈNE-6-ONES ET ANALOGUES POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2014188440A1

  公开（公告）日：2014-11-27

  The present invention relates to 2,3,4,4a-tetrahydro-3,4,8,10-tetrahydroxy-2- (hydroxymethyl)-9-methoxypyrano[3,2-c]isochromen-6(10bH)-one analogs of the Formula I, wherein, R, R' and R" are as herein described. In addition, the invention relates to methods of using compounds for treating or preventing various inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, asthma and chronic obstructive pulmonary disorder.

  本发明涉及式I中的2,3,4,4a-四氢-3,4,8,10-四羟基-2-(羟甲基)-9-甲氧基吡喃[3,2-c]异色素-6(10bH)-酮类似物，其中，R、R'和R"如本文所述。此外，本发明涉及使用化合物治疗或预防各种炎症性疾病，如类风湿性关节炎、炎症性肠病、银屑病、哮喘和慢性阻塞性肺疾病的方法。
• 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.