(1S,5R)-3-(3α-hydroxy-6,8-dioxabicyclo[3.2.1]octan-3-yl)benzyl alcohol | 153607-80-8

• 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: (1S,5R)-3-(3α-hydroxy-6,8-dioxabicyclo[3.2.1]octan-3-yl)benzyl alcohol
• 英文别名: (1S,3S,5R)-3-[3-(hydroxymethyl)phenyl]-6,8-dioxabicyclo[3.2.1]octan-3-ol
• CAS: 153607-80-8
• 化学式: C₁₃H₁₆O₄
• 分子量: 236.268
• InChiKey: IRVWDBCWNZOVOZ-XQQFMLRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  58.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,5R)-3-(3α-hydroxy-6,8-dioxabicyclo[3.2.1]octan-3-yl)benzyl alcohol 在 sodium hydroxide 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 乙醇 为溶剂， 反应 18.08h， 生成
  参考文献：
  名称：

  Dioxabicyclooctanyl Naphthalenenitriles as Nonredox 5-Lipoxygenase Inhibitors:  Structure−Activity Relationship Study Directed toward the Improvement of Metabolic Stability

  摘要：

  Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicydo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B-4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).

  DOI：

  10.1021/jm960301c
• 作为产物：
  描述：

  1,6-anhydro-2,4-dideoxy-β-D-glycero-hexopyranos-3-ulose 在 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 (1S,5R)-3-(3α-hydroxy-6,8-dioxabicyclo[3.2.1]octan-3-yl)benzyl alcohol
  参考文献：
  名称：

  Dioxabicyclooctanyl Naphthalenenitriles as Nonredox 5-Lipoxygenase Inhibitors:  Structure−Activity Relationship Study Directed toward the Improvement of Metabolic Stability

  摘要：

  Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicydo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B-4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).

  DOI：

  10.1021/jm960301c

文献信息

• Quinolines as potent 5-lipoxygenase inhibitors: Synthesis and biological profile of L-746,530
  作者：Daniel Dubé、Marc Blouin、Christine Brideau、Chi-Chung Chan、Sylvie Desmarais、Diane Ethier、Jean-Pierre Falgueyret、Richard W. Friesen、Mario Girard、Yves Girard、Jocelyne Guay、Denis Riendeau、Philip Tagari、Robert N. Young

  DOI：10.1016/s0960-894x(98)00201-7

  日期：1998.5

  Leukotriene biosynthesis inhibitors have potential as new therapeutic agents for asthma and inflammatory diseases. A series of novel substituted 2-cyanoquinolines have been synthesized and the structure activity relationships were evaluated with respect to their ability to inhibit the formation of leukotrienes via the 5-lipoxygenase enzyme. [1S,5R]-2-Cyano-4-(3-furyl)-7-¿3-fluoro-5-[3-(3 alpha-hydroxy-6

  白三烯生物合成抑制剂作为哮喘和炎性疾病的新治疗剂具有潜力。已经合成了一系列新颖的取代的2-氰基喹啉，并就它们通过5-脂氧合酶抑制白三烯形成的能力评估了结构活性关系。[1S，5R] -2-氰基-4-（3-呋喃基）-7-¿3-氟-5- [3-（3α-羟基-6,8-二氧杂双环[3.2.1]-辛基）]苯氧基甲基喹啉（L-746,530）3代表一类独特的抑制剂，其体外和体内效价与萘类似物（L-739,010）2相当或更高。