methyl 4-benzyl-7-methoxy-2-naphthoate | 181276-09-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 4-benzyl-7-methoxy-2-naphthoate
• 英文别名: Methyl 4-benzyl-7-methoxynaphthalene-2-carboxylate
• CAS: 181276-09-5
• 化学式: C₂₀H₁₈O₃
• 分子量: 306.361
• InChiKey: UJXHSPPVAATRRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 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：

  methyl 4-benzyl-7-methoxy-2-naphthoate 在 吡啶盐酸盐 作用下， 以 乙醚 为溶剂， 反应 0.5h， 生成 Methyl 4-benzyl-7-hydroxynaphthalene-2-carboxylate
  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：

  7-Methoxy-4-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid ethyl ester 在 camphor-10-sulfonic acid 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 乙醚 、 苯 为溶剂， 反应 4.5h， 生成 methyl 4-benzyl-7-methoxy-2-naphthoate
  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

• A novel tandem Pd-catalyzed intramolecular allylic decarboxylative coupling and “diradical conjugated 1,3-dien-5-yne cycloaromatization”: An unusual ortho -selectivity in the cycloaromatization and the mechanistic implications
  作者：Satyanarayana Tummanapalli、Dhanunjaya Naidu Vangapandu、Parthasarathy Muthuraman、Sanjeeva Kambampati、Gnanakalai Shanmugavel

  DOI：10.1016/j.tetlet.2017.06.079

  日期：2017.8

  hindered cyclization products (12–23) via the unusual ortho-selective cycloaromatization; while the meta-alkoxy (1i–m, 1r–t) group provided predominantly the ortho-selective 1,3-dien-5-yne cycloaromatization products, meta-Me group (1 n–q), products formed both via ortho-selective cyclization and para-selective cyclization products in comparable ratio. A novel mechanism involving diradical species

  在催化Pd（PPh 3）4和DBU的存在下，Baylis-Hillman醇的丙酸芳基酯的多米诺骨化烯丙基重排，分子内脱羧偶联，炔丙基-丙二烯重排和双自由基1,3-二烯-5-炔环芳构化已经描述了4-苄基萘甲酸的形成。有趣的是，间位取代的丙酸酯（1i – t）通过不寻常的邻位选择性环芳烃化作用提供了空间位阻的环化产物（12 – 23）。而间烷氧基（1i – m，1r –t）组主要提供邻位选择性1,3-二烯基-5yne环芳烃化产品，meta -Me组（1  n – q），是通过邻位选择性环化和对位选择性环化产物以可比的比例形成的产物。已经提出了一种涉及双自由基物种的新机制来解释1，3-二烯-5-炔环芳构化中不寻常的邻位选择性。空间上受阻的邻位选择性环化的优先选择可能归因于具有更稳定的邻位甲氧基环己二烯基团部分（驱动力）的过渡态自由基的形成。
• The Baylis–Hillman acetates in organic synthesis: Unprecedented sodium nitrite induced intramolecular Friedel–Crafts cyclization of secondary nitro compounds
  作者：Deevi Basavaiah、Daggula Mallikarjuna Reddy

  DOI：10.1039/c4ra03573a

  日期：——

  Unprecedented sodium nitrite mediated intramolecular Friedel–Crafts cyclization of alkyl (E)-2-arylidene-4-nitroalkanoates and (E)-3-arylidene-5-nitroalkan-2-ones derived from Baylis–Hillman acetates, providing a facile protocol for synthesis of naphthalenes, phenanthrenes, and carbazoles has been described.

  前所未有的亚硝酸钠介导的Bayes-Hillman乙酸酯衍生的烷基（E）-2-芳基亚烷基-4-硝基链烷酸酯和（E）-3-芳基亚烷基5-硝基醛烷-2-酮的分子内Friedel-Crafts环化已经描述了萘，菲和咔唑的合成。
• Dioxabicyclooctanyl Naphthalenenitriles as Nonredox 5-Lipoxygenase Inhibitors:  Structure−Activity Relationship Study Directed toward the Improvement of Metabolic Stability
  作者：Daniel Delorme、Yves Ducharme、Christine Brideau、Chi-Chung Chan、Nathalie Chauret、Sylvie Desmarais、Daniel Dubé,、Jean-Pierre Falgueyret、Réjean Fortin、Jocelyne Guay、Pierre Hamel、Tom R. Jones、Carole Lépine、Chun Li、Malia McAuliffe、Cyril S. McFarlane、Deborah A. Nicoll-Griffith、Denis Riendeau、James A. Yergey、Yves Girard

  DOI：10.1021/jm960301c

  日期：1996.1.1

  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).