(2S)-(-)-2-<methyl>-7-(4-fluorophenoxy)-1,4-benzodioxan

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S)-(-)-2-<methyl>-7-(4-fluorophenoxy)-1,4-benzodioxan
• 英文别名: (2S)-2-[[N-(aminocarbonyl)-N-hydroxyamino]methyl]-7-(4-fluorophenoxy)-1,4-benzodioxan；1-[[(3S)-6-(4-fluorophenoxy)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]-1-hydroxyurea
• 化学式: C₁₆H₁₅FN₂O₅
• 分子量: 334.304
• InChiKey: YKFHRCWEMNKISZ-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  94.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  三甲基硅基异氰酸酯 、 N-[(S)-7-(4-Fluoro-phenoxy)-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl]-hydroxylamine 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 (2S)-(-)-2-<methyl>-7-(4-fluorophenoxy)-1,4-benzodioxan
  参考文献：
  名称：

  Derivatives of 2-[[N-(Aminocarbonyl)-N-hydroxyamino]methyl]-1,4-benzodioxan as Orally Active 5-Lipoxygenase Inhibitors

  摘要：

  N-Hydroxyureas based on the 1,4-benzodioxan template were prepared from appropriately substituted 1,4-benzodioxan-2-methanols as the key intermediates and evaluated in the in vitro guinea pig polymorphonuclear leukocyte 5-lipoxygenase (5-LO) assay for their 5-LO inhibitory activity. Placement of a 7-phenoxy or 7-p-fluorophenoxy substituent resulted in a dramatic increase in in vitro potency. Selected compounds were subsequently assayed in an ex vivo dog model of LTB(4) synthesis at a dose of 1.0 mg/kg. The 7-phenoxy derivatives 16 and 17 showed modest duration of action (DA) in this dog model. The g-regioisomers 21 and 22 were less potent. Replacement of the 7-phenoxy group of 16 with the p-fluorophenoxy moiety enhanced the DA dramatically. Compound 18 (CGS 25667), which had an IC50 value of 100 nM in the in vitro guinea pig 5-LO assay, had a DA of 8.5 h (zileuton, DA = 8.5 h) at the oral dose of 1.0 mg/kg. Optical antipodes (24, 26) of 18 were independently synthesized in high (>95%) enantiomeric purity from commercially available optically active glycidyl tosylates and evaluated. In the in vitro assay, the 2S-(-)-enantiomer (24, CGS 25997, IC50 = 85 nM) was found to be twice as active as the 2R-(+)-counterpart (26, CGS 25998, IC50 - 180 nM). In the ex vivo experiment, 24, which dose dependently inhibited plasma 5-LO activity, was shown to be significantly longer acting than 26, with a DA of 8.4 h when dosed orally at 1.0 mg/kg.

  DOI：

  10.1021/jm00001a012

文献信息

• Use of Ltb4 Inhibitors for the Treatment of B-Cell Leukemias and Lymphomas
  申请人：Claesson Hans-Erik

  公开号：US20080081835A1

  公开（公告）日：2008-04-03

  The invention relates to the use of an inhibitor of the biosynthesis and/or function of LTB 4 for the manufacture of a medicament for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), B-prolymphocytic leukemia (B-PLL) or B-cell lymphoma. Preferably, the inhibitor of the biosynthesis and/or function of LTB 4 is the inhibitor of 5-LO BWA4C or the inhibitor of FLAP MK-886.
• Method and composition for treating inflammatory disorders
  申请人：Pereswetoff-Morath Lena

  公开号：US20090220583A1

  公开（公告）日：2009-09-03

  There is provided homogeneous pharmaceutical compositions for the treatment of inflammatory disorders comprising an antiinflammatory and/or antihistaminic active ingredient, a polar lipid liposome and a pharmaceutically-acceptable aqueous carrier.
• Method and Composition for Treating Inflammatory Disorders
  申请人：Meda AB

  公开号：US20160166508A1

  公开（公告）日：2016-06-16

  There is provided homogeneous pharmaceutical compositions for the treatment of inflammatory disorders comprising an antiinflammatory and/or antihistaminic active ingredient, a polar lipid liposome and a pharmaceutically-acceptable aqueous carrier.
• Derivatives of 2-[[N-(Aminocarbonyl)-N-hydroxyamino]methyl]-1,4-benzodioxan as Orally Active 5-Lipoxygenase Inhibitors
  作者：Yoshitaka Satoh、Colleen Powers、Leticia M. Toledo、Timothy J. Kowalski、Paul A. Peters、Earl F. Kimble

  DOI：10.1021/jm00001a012

  日期：1995.1

  N-Hydroxyureas based on the 1,4-benzodioxan template were prepared from appropriately substituted 1,4-benzodioxan-2-methanols as the key intermediates and evaluated in the in vitro guinea pig polymorphonuclear leukocyte 5-lipoxygenase (5-LO) assay for their 5-LO inhibitory activity. Placement of a 7-phenoxy or 7-p-fluorophenoxy substituent resulted in a dramatic increase in in vitro potency. Selected compounds were subsequently assayed in an ex vivo dog model of LTB(4) synthesis at a dose of 1.0 mg/kg. The 7-phenoxy derivatives 16 and 17 showed modest duration of action (DA) in this dog model. The g-regioisomers 21 and 22 were less potent. Replacement of the 7-phenoxy group of 16 with the p-fluorophenoxy moiety enhanced the DA dramatically. Compound 18 (CGS 25667), which had an IC50 value of 100 nM in the in vitro guinea pig 5-LO assay, had a DA of 8.5 h (zileuton, DA = 8.5 h) at the oral dose of 1.0 mg/kg. Optical antipodes (24, 26) of 18 were independently synthesized in high (>95%) enantiomeric purity from commercially available optically active glycidyl tosylates and evaluated. In the in vitro assay, the 2S-(-)-enantiomer (24, CGS 25997, IC50 = 85 nM) was found to be twice as active as the 2R-(+)-counterpart (26, CGS 25998, IC50 - 180 nM). In the ex vivo experiment, 24, which dose dependently inhibited plasma 5-LO activity, was shown to be significantly longer acting than 26, with a DA of 8.4 h when dosed orally at 1.0 mg/kg.