1,6-anhydro-2,4-dideoxy-β-D-glycero-hexopyranos-3-ulose | 30923-34-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧杂环己烷
• 英文名称: 1,6-anhydro-2,4-dideoxy-β-D-glycero-hexopyranos-3-ulose
• 英文别名: 1,6-anhydro-2,4-dideoxy-β-D-glycerohexopyranos-3-ulose；(1S,3S,5R)-6,8-dioxabicyclo<3.2.1>octan-3-one；(1S,5R)-6,8-dioxabicyclo<3.2.1>octan-3-one；[1 S,3S,5R]6,8-Dioxabicyclo[3.2.1]octan-3-one；(1S,5R) 6,8-dioxabicyclo[3.2.1]octan-3-one；[1S,5R] 6,8-dioxabicyclo[3.2.1]octan-3-one；(1S,5R)-6,8-dioxabicyclo[3.2.1]octan-3-one
• CAS: 30923-34-3
• 化学式: C₆H₈O₃
• 分子量: 128.128
• InChiKey: HCXQQQLFLDDUNB-NTSWFWBYSA-N

物化性质

• 沸点：
  218.7±25.0 °C(Predicted)
• 密度：
  1.261±0.06 g/cm3(Predicted)

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：

  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
• 作为产物：
  描述：

  1,6-脱水-β-D-葡萄糖 在 吡啶 、 ruthenium trichloride 、 sodium bromate 、 锌 作用下， 以 四氢呋喃 、 水 、 溶剂黄146 、 乙腈 为溶剂， 反应 15.5h， 生成 1,6-anhydro-2,4-dideoxy-β-D-glycero-hexopyranos-3-ulose
  参考文献：
  名称：

  Practical Synthesis of 1,6-Anhydro-2,4-dideoxy-β-d-glycero- hexopyranos-3-ulose from Levoglucosan

  摘要：

  DOI：

  10.1021/jo991719w

文献信息

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

  公开号：US05308852A1

  公开（公告）日：1994-05-03

  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.

  具有公式I: ##STR1## 的化合物是白三烯生物合成抑制剂。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、脑痉挛、肾小球肾炎、肝炎、内毒素血症、葡萄膜炎和移植排斥，并可预防动脉粥样硬化斑块的形成。
• Phenylnaphthalene lactones as inhibitors of leukotriene biosynthesis
  申请人：Merck Frosst Canada, Inc.

  公开号：US05350744A1

  公开（公告）日：1994-09-27

  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.

  具有以下化学式的化合物I：##STR1## 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、脑痉挛、肾小球肾炎、肝炎、内毒素血症、葡萄膜炎和移植排斥，以及预防动脉粥样硬化斑块的形成。
• Phenylnaphthalene hydroxy acids
  申请人：Merck Frosst Canada, Inc.

  公开号：US05426109A1

  公开（公告）日：1995-06-20

  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.

  具有化学式I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、脑痉挛、肾小球肾炎、肝炎、内毒素血症、葡萄膜炎和移植排斥，并可预防动脉粥样硬化斑块的形成。
• [EN] HETEROARYLNAPHTHALENES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS<br/>[FR] HETEROARYLNAPHTALENES UTILISES COMME INHIBITEURS DE LA BIOSYNTHESE DE LEUCOTRIENE
  申请人：MERCK FROSST CANADA INC.

  公开号：WO1994000444A1

  公开（公告）日：1994-01-06

  (EN) Compounds having formula (I), 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.(FR) Composés répondant à la formule (I), et servant d'inhibiteurs de la biosynthèse de leucotriène. Ces composés sont utiles en tant qu'agents antiasthmatiques, antiallergiques, anti-inflammatoires et cytoprotecteurs. Ils sont également utiles dans le traitement de l'angine, du spasme cérébral, de la glomérulonéphrite, de l'hépatite, de l'endotoxémie, de l'uvéite et du rejet d'allogreffe, ainsi que dans la prévention de la formation de plaques athéroscléreuses.

  化合物具有公式（I），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，脑痉挛，肾小球肾炎，肝炎，内毒素血症，葡萄膜炎和同种异体移植排斥，并防止动脉粥样硬化斑块的形成。
• Substituted (Pyridylmethoxy)naphthalenes as Potent and Orally Active 5-Lipoxygenase Inhibitors:  Synthesis, Biological Profile, and Pharmacokinetics of L-739,010
  作者：Pierre Hamel、Denis Riendeau、Christine Brideau、Chi-Chung Chan、Sylvie Desmarais、Daniel Delorme、Daniel Dubé、Yves Ducharme、Diane Ethier、Erich Grimm、Jean-Pierre Falgueyret、Jocelyne Guay、Tom R. Jones、Elizabeth Kwong、Malia McAuliffe,、Cyril S. McFarlane、Hanna Piechuta、Marie Roumi、Philip Tagari、Robert N. Young、Yves Girard

  DOI：10.1021/jm970046b

  日期：1997.8.1

  Dioxabicyclooctanyl naphthalenenitriles have been reported as a class of potent and nonredox 5-lipoxygenase (5-LO) inhibitors. These bicycle derivatives were shown to be metabolically more stable than their tetrahydropyranyl counterparts but were not well orally absorbed. Replacement of the phenyl ring in the naphthalenenitrile 1 by a pyridine ring leads to the potent and orally absorbed inhibitor 3g (L-739,010, 2-cyano-4-(3-furyl)-7-[[6-[3-(3-hydroxy-6,8-dioxabicyclo[3.2.1] octanyl)]-2-pyridyl]methoxy]naphthalene). Compound 3g inhibits 5-HPETE production by human 5-LO and LTB4 biosynthesis by human PMN leukocytes and human whole blood (IC(50)s of 20, 1.6, and 42 nM, respectively). Derivative 3g is orally active in the rat pleurisy model (inhibition of LTB4, ED50 = 0.3 mg/kg) and in the anesthetized dog model (inhibition of ex vivo whole blood LTB4 and urinary LTE4, ED50 = 0.45 and 0.23 mu g/kg/min, respectively, iv infusion). In addition, 3g shows excellent functional activity against ovalbumin-induced dyspnea in rats (60% inhibition at 0.5 mg/kg, 4 h pretreatment) and Ascaris-induced bronchoconstriction in conscious sheep (50% and >85% inhibition in early and late phases, respectively at 2.5 mu g/kg/min, iv infusion) and, more particularly in the conscious antigen sensitive squirrel monkey model (53% inhibition of the increase in R-L and 76% in the decrease of C-dyn, at 0.1 mg/kg, po). In rats and dogs, 3g presents excellent pharmacokinetics (estimated half-lives of 5 and 16 h, respectively) and bioavailabilities (26% and 73% when dosed as its hydrochloride salt at doses of 20 and 10 mg/kg, respectively, in methocel suspension). Based on its overall biological profile, compound 3g has been selected for preclinical animal toxicity studies.