2-cyano-4-(3-furyl)-7-(hydroxymethyl)naphthalene | 172403-28-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-cyano-4-(3-furyl)-7-(hydroxymethyl)naphthalene
• 英文别名: 4-(Furan-3-yl)-7-(hydroxymethyl)naphthalene-2-carbonitrile
• CAS: 172403-28-0
• 化学式: C₁₆H₁₁NO₂
• 分子量: 249.269
• InChiKey: ZCQNJYCGJKQOOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-cyano-4-(3-furyl)-7-(hydroxymethyl)naphthalene 、 2-bromo-6-[3-(3-hydroxy-6,8-dioxabicyclo[3.2.1]octanyl)]pyridine 在 sodium hydroxide 、 18-冠醚-6 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以51%的产率得到2-cyano-4-(3-furyl)-7-[({6-[3-(3-hydroxy-6.8-dioxabicyclo[3.2.1]octanyl)]-2-pyridyl}oxy)methyl]naphthalene
  参考文献：
  名称：

  Substituted (Pyridylmethoxy)naphthalenes as Potent and Orally Active 5-Lipoxygenase Inhibitors:  Synthesis, Biological Profile, and Pharmacokinetics of L-739,010

  摘要：

  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.

  DOI：

  10.1021/jm970046b
• 作为产物：
  描述：

  methyl 2-cyano-4-(3-furyl)-7-naphthoate 在 锂硼氢 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以58%的产率得到2-cyano-4-(3-furyl)-7-(hydroxymethyl)naphthalene
  参考文献：
  名称：

  Substituted (Pyridylmethoxy)naphthalenes as Potent and Orally Active 5-Lipoxygenase Inhibitors:  Synthesis, Biological Profile, and Pharmacokinetics of L-739,010

  摘要：

  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.

  DOI：

  10.1021/jm970046b

文献信息

• BISARYLCARBINOL DERIVATIVES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS
  申请人：Merck Frosst Canada & Co.

  公开号：EP0788497B1

  公开（公告）日：2001-05-23
• US5552437A
  申请人：——

  公开号：US5552437A

  公开（公告）日：1996-09-03
• [EN] BISARYLCARBINOL DERIVATIVES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS<br/>[FR] DERIVES DE BISARYLCARBINOL UTILISES COMME INHIBITEURS DE LA BIOSYNTHESE DES LEUCOTRIENES
  申请人：MERCK FROSST CANADA INC.

  公开号：WO1996013500A1

  公开（公告）日：1996-05-09

  (EN) Compounds having the formula (I): R1R2C(OR3)-Ar1-X-Ar2-Ar3 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) L'invention se rapporte à des composés de la formule (I): R1R2C(OR3)-Ar1-X-Ar2-Ar3, qui sont des inhibiteurs de la biosynthèse des leucotriènes. Ces composés sont utiles comme agents anti-asthmatiques, anti-allergiques, anti-inflammatoires et cytoprotecteurs. Ils sont également utiles dans le traitement des angines, des spasmes cérébraux, des néphrites glomérulaires, de l'hépatite, de l'endotoxémie, de l'uvéite et des rejets d'allogreffes et dans la prévention de la formation de plaques athéroscléreuses.
• 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.