HIR-3 | 116718-59-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: HIR-3
• 英文别名: 3,4-dihydro-6,7-dihydroxy-3-(4-methylphenyl)-2H-1-benzopyran；6,7-Dihydroxy-4'-methylisoflavan；3-(4-methylphenyl)-3,4-dihydro-2H-chromene-6,7-diol
• CAS: 116718-59-3
• 化学式: C₁₆H₁₆O₃
• 分子量: 256.301
• InChiKey: OKUSEYCLSBRHFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1,2,4-苯三酚 在 盐酸 、 硫酸 、 palladium 10% on activated carbon 、 三氟化硼乙醚 、 水 、 甲基磺酰氯 、 zinc(II) chloride 作用下， 以 乙醚 、 溶剂黄146 为溶剂， 反应 2.0h， 生成 HIR-3
  参考文献：
  名称：

  Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5-Lipo-Oxygenase

  摘要：

  Continuing our search to find more potent and selective 5‐LOX inhibitors, we present now the enzymatic evaluation of seventeen isoflavones (IR) and nine isoflavans (HIR), and their in vitro and in cellulo potency against human leukocyte 5‐LOX. Of the 26 compounds tested, 10 isoflavones and 9 isoflavans possessed micromolar potency, but only three were selective against 5‐LOX (IR‐2, HIR‐303, and HIR‐309), with IC50 values at least 10 times lower than those of 12‐LOX, 15‐LOX‐1, and 15‐LOX‐2. Of these three, IR‐2 (6,7‐dihydroxy‐4‐methoxy‐isoflavone, known as texasin) was the most selective 5‐LOX inhibitor, with over 80‐fold potency difference compared with other isozymes; Steered Molecular Dynamics (SMD) studies supported these findings. The presence of the catechol group on ring A (6,7‐dihydroxy versus 7,8‐dihydroxy) correlated with their biological activity, but the reduction of ring C, converting the isoflavones to isoflavans, and the substituent positions on ring B did not affect their potency against 5‐LOX. Two of the most potent/selective inhibitors (HIR‐303 and HIR‐309) were reductive inhibitors and were potent against 5‐LOX in human whole blood, indicating that isoflavans can be potent and selective inhibitors against human leukocyte 5‐LOX in vitro and in cellulo.

  DOI：

  10.1111/cbdd.12469

文献信息

• Bicyclic compounds
  申请人：Zyma SA

  公开号：EP0267155A2

  公开（公告）日：1988-05-11

  Isoflavans of the formula I wherein the groups OR, R', R" and ring B are as defined in the specification, exhibit valueable pharmacological properties, especially for the treatment of vascular diseases. They are prepared by methods known per se.

  式 I 的异黄酮（其中基团 OR、R'、R "和环 B 如说明书中所定义）具有宝贵的药理特性，特别是在治疗血管疾病方面。 它们是通过本身已知的方法制备的。
• US4814346A
  申请人：——

  公开号：US4814346A

  公开（公告）日：1989-03-21
• Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5-Lipo-Oxygenase
  作者：Carolina Mascayano、Victoria Espinosa、Silvia Sepúlveda-Boza、Eric K. Hoobler、Steve Perry、Giovanni Diaz、Theodore R. Holman

  DOI：10.1111/cbdd.12469

  日期：2015.7

  Continuing our search to find more potent and selective 5‐LOX inhibitors, we present now the enzymatic evaluation of seventeen isoflavones (IR) and nine isoflavans (HIR), and their in vitro and in cellulo potency against human leukocyte 5‐LOX. Of the 26 compounds tested, 10 isoflavones and 9 isoflavans possessed micromolar potency, but only three were selective against 5‐LOX (IR‐2, HIR‐303, and HIR‐309), with IC50 values at least 10 times lower than those of 12‐LOX, 15‐LOX‐1, and 15‐LOX‐2. Of these three, IR‐2 (6,7‐dihydroxy‐4‐methoxy‐isoflavone, known as texasin) was the most selective 5‐LOX inhibitor, with over 80‐fold potency difference compared with other isozymes; Steered Molecular Dynamics (SMD) studies supported these findings. The presence of the catechol group on ring A (6,7‐dihydroxy versus 7,8‐dihydroxy) correlated with their biological activity, but the reduction of ring C, converting the isoflavones to isoflavans, and the substituent positions on ring B did not affect their potency against 5‐LOX. Two of the most potent/selective inhibitors (HIR‐303 and HIR‐309) were reductive inhibitors and were potent against 5‐LOX in human whole blood, indicating that isoflavans can be potent and selective inhibitors against human leukocyte 5‐LOX in vitro and in cellulo.