(+/-)-N-hydroxy-N-[2,3-dihydro-6-(benzyloxy)benzofuran-3-yl]urea | 184575-08-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: (+/-)-N-hydroxy-N-[2,3-dihydro-6-(benzyloxy)benzofuran-3-yl]urea
• 英文别名: N-Hydroxy-N-[2,3-dihydro-6-(benzyloxy)benzofuran-3-yl]urea；1-hydroxy-1-(6-phenylmethoxy-2,3-dihydro-1-benzofuran-3-yl)urea
• CAS: 184575-08-4
• 化学式: C₁₆H₁₆N₂O₄
• 分子量: 300.314
• InChiKey: FYAQEFBDKOWIIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 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：
  85
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-N-hydroxy-N-[2,3-dihydro-6-(benzyloxy)benzofuran-3-yl]urea 生成 苯甲醇,-α--甲基-4-(2-甲基丙基)-,乙酸酯(9CI)
  参考文献：
  名称：

  Bicyclic N-Hydroxyurea Inhibitors of 5-Lipoxygenase:  Pharmacodynamic, Pharmacokinetic, and in Vitro Metabolic Studies Characterizing N-Hydroxy-N-(2,3-dihydro-6-(phenylmethoxy)-3-benzofuranyl)urea

  摘要：

  A series of N-hydroxyurea derivatives have been prepared and examined as inhibitors of 5-lipoxygenase. Oral activity was established by examining the inhibition of LTB(4) biosynthesis in an ex vivo assay in the mouse. The pharmacodynamic performance in the mouse of selected compounds was assessed using an ex vivo LTB(4) assay and an adoptive peritoneal anaphylaxis assay at extended pretreat times. Compounds with an extended duration of action were reexamined as the individual enantiomers in the ex vivo assay, and the (S) enantiomer of N-hydroxy-N-[2,3-dihydro-6-(phenylmethoxy)-3-benzofuranyl]urea, (+)-1a (SE 202235), was selected as the compound with the best overall profile. Higher plasma concentrations and longer plasma half-lives were found for (+)-1a relative to its enantiomer in the mouse, monkey, and dog. In vitro metabolic studies in mouse liver microsomes established enantiospecific glucuronidation as a likely mechanism for the observed differences between the enantiomers of la. Enantioselective glucuronidation favoring (-)-1a was also found in human liver microsomes.

  DOI：

  10.1021/jm960271d
• 作为产物：
  描述：

  (E/Z)-6-benzyloxy-2,3-dihydrobenzofuran-3-oxime 在 盐酸 、 吡啶硼烷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 (+/-)-N-hydroxy-N-[2,3-dihydro-6-(benzyloxy)benzofuran-3-yl]urea
  参考文献：
  名称：

  Bicyclic N-Hydroxyurea Inhibitors of 5-Lipoxygenase:  Pharmacodynamic, Pharmacokinetic, and in Vitro Metabolic Studies Characterizing N-Hydroxy-N-(2,3-dihydro-6-(phenylmethoxy)-3-benzofuranyl)urea

  摘要：

  A series of N-hydroxyurea derivatives have been prepared and examined as inhibitors of 5-lipoxygenase. Oral activity was established by examining the inhibition of LTB(4) biosynthesis in an ex vivo assay in the mouse. The pharmacodynamic performance in the mouse of selected compounds was assessed using an ex vivo LTB(4) assay and an adoptive peritoneal anaphylaxis assay at extended pretreat times. Compounds with an extended duration of action were reexamined as the individual enantiomers in the ex vivo assay, and the (S) enantiomer of N-hydroxy-N-[2,3-dihydro-6-(phenylmethoxy)-3-benzofuranyl]urea, (+)-1a (SE 202235), was selected as the compound with the best overall profile. Higher plasma concentrations and longer plasma half-lives were found for (+)-1a relative to its enantiomer in the mouse, monkey, and dog. In vitro metabolic studies in mouse liver microsomes established enantiospecific glucuronidation as a likely mechanism for the observed differences between the enantiomers of la. Enantioselective glucuronidation favoring (-)-1a was also found in human liver microsomes.

  DOI：

  10.1021/jm960271d

文献信息

• Resolution of hydroxyureas
  作者：Ravi S. Garigipati、Margaret E. Sorenson、Karl F. Erhard、Jerry L. Adams

  DOI：10.1016/s0040-4039(00)73875-5

  日期：1993.8

  Racemic hydroxyureas can be efficiently resolved on a preparative scale using (4S)-4-benzyl-2-oxazolidinone-3-carbonyl chloride 3. The resulting carbamates can be separated by chromatography and hydrolysis of these diastereomers yields enantiomerically pure hydroxyureas.
• SYNTHESIS OF ACID ADDITION SALTS OF HYDROXYLAMINES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0708753A1

  公开（公告）日：1996-05-01
• EP0708753A4
  申请人：——

  公开号：EP0708753A4

  公开（公告）日：1996-10-02
• US5663368A
  申请人：——

  公开号：US5663368A

  公开（公告）日：1997-09-02
• [EN] SYNTHESIS OF ACID ADDITION SALTS OF HYDROXYLAMINES<br/>[FR] SYNTHESE DE SELS D'ADDITION D'ACIDE D'HYDROXYLAMINES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：WO1995002574A1

  公开（公告）日：1995-01-26

  (EN) This invention relates to novel diastereoisomeric acid addition salts of homochiral hydroxylamines, to processes for obtaining such, to processes for the conversion thereof to the corresponding homochiral hydroxylamines, to certain novel homochiral hydroxylamines and to processes for using these as intermediates.(FR) L'invention concerne de nouveaux sels d'addition d'acide diastéréoisomères d'hydroxylamines homochirales, des procédés d'obtention de ceux-ci, des procédés permettant leur conversion en hydroxylamines monochirales correspondantes, certaines hydroxylamines homochirales nouvelles et des procédés d'utilisation de celles-ci comme produits intermédiaires.