6,8-二氧杂二环[3.2.1]辛烷-3-酮,(1R)- | 153667-43-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧杂环己烷
• 中文名称: 6,8-二氧杂二环[3.2.1]辛烷-3-酮,(1R)-
• 英文名称: (1R,5S)-6,8-dioxabicyclo<3.2.1>octan-3-one
• 英文别名: [1R,5S]6,8-dioxabicyclo[3.2.1]octan-3-one；(1R,5S) 6,8-dioxabicyclo[3.2.1]octane-3-one；(1R,5S)-6,8-dioxabicyclo[3.2.1]octan-3-one
• CAS: 153667-43-7
• 化学式: C₆H₈O₃
• 分子量: 128.128
• InChiKey: HCXQQQLFLDDUNB-RITPCOANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6,8-二氧杂二环[3.2.1]辛烷-3-酮,(1R)- 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 (1R,5S)-3-(3-α-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
• 作为产物：
  描述：

  [(8R)-10-hydroxy-9-oxa-1,5-dithiaspiro[5.5]undecan-8-yl]methyl 4-methylbenzenesulfonate 在 高氯酸亚汞 、 溴脲苷 、 calcium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 60.5h， 生成 6,8-二氧杂二环[3.2.1]辛烷-3-酮,(1R)-
  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

• Arylbicyclooctanes as inhibitors of leukotriene biosynthesis
  申请人：Merck Frosst Canada, Inc.

  公开号：US05459271A1

  公开（公告）日：1995-10-17

  Compounds having the formula I: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis and allograft rejection and in preventing the formation of atherosclerotic plaques.

  公式为I：##STR1##的化合物是白三烯生物合成的抑制剂。这些化合物可用作抗哮喘、抗过敏、抗炎和细胞保护剂。它们还可用于治疗心绞痛、脑血管痉挛、肾小球肾炎、肝炎、内毒素血症、葡萄膜炎和移植排斥，并防止动脉粥样硬化斑块的形成。
• A study of the lithiation of 2,6-dibromopyridine with butyllithium, and its application to synthesis of L-739,010
  作者：Dongwei Cai、David L. Hughes、Thomas R. Verhoeven

  DOI：10.1016/0040-4039(96)00336-x

  日期：1996.4

  Mono-lithiation of 2,6-dibromopyridine by n-BuLi is complicated by deprotonation of the pyridine ring by the resulting mono-lithium species. This problem can be eliminated by a reverse addition, but this causes formation of the undesired dilithio species. However, rapid lithium-halogen exchange between 2,6-dibromopyridine and 2,6-dilithiopyridine produces 2-brom-6-lithiopyridine cleanly. Thus, using reverse addition, the mono-lithiated pyridine can be generated in 98% yield. Copyright (C) 1996 Elsevier Science Ltd
• US5252599A
  申请人：——

  公开号：US5252599A

  公开（公告）日：1993-10-12
• US5428060A
  申请人：——

  公开号：US5428060A

  公开（公告）日：1995-06-27
• US5459271A
  申请人：——

  公开号：US5459271A

  公开（公告）日：1995-10-17