1-hydroxy-1-(6-phenylmethoxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-3-yl)urea | 146827-27-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-hydroxy-1-(6-phenylmethoxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-3-yl)urea
• CAS: 146827-27-2
• 化学式: C₁₉H₁₉N₃O₃
• 分子量: 337.378
• InChiKey: OLQZOGIEDMKSOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  80.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4(S)-N-chloroformyl-4-isopropyl-2-oxazolidinone 、 1-hydroxy-1-(6-phenylmethoxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-3-yl)urea 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 1-((S)-7-(benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)-1-(((S)-4-isopropyl-2-oxooxazolidine-3-carbonyl)oxy)urea 、
  参考文献：
  名称：

  Resolution of hydroxyureas

  摘要：

  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.

  DOI：

  10.1016/s0040-4039(00)73875-5
• 作为产物：
  描述：

  7-Benzyloxy-1-oxo-2,3-dihydro-1H-pyrrolo<1,2-a>indol-oxim 在 盐酸 、 吡啶硼烷 作用下， 以 四氢呋喃 为溶剂， 生成 1-hydroxy-1-(6-phenylmethoxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-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

• [EN] LIPOXYGENASE INHIBITING PYRROLO [1,2a]INDOLE COMPOUNDS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：WO1992021678A1

  公开（公告）日：1992-12-10

  (EN) Pyrrolo[1,2-a]indole hydroxyurea/hydroxamate compounds, pharmaceutical compositions containing said compounds and their use as inhibitors of oxygenated polyunsaturated fatty acid metabolism.(FR) Composés d'hydroxamate/hydroxyurée de pyrrolo[1,2-a]indole, compositions pharmaceutiques contenant lesdits composés et leur utilisation comme inhibiteurs du métabolisme des acides gras oxygénés eet polyinsaturés.
• Bicyclic N-Hydroxyurea Inhibitors of 5-Lipoxygenase:  Pharmacodynamic, Pharmacokinetic, and <i>in Vitro</i> Metabolic Studies Characterizing <i>N</i>-Hydroxy-<i>N</i>-(2,3-dihydro-6-(phenylmethoxy)-3-benzofuranyl)urea
  作者：Jerry L. Adams、Ravi S. Garigipati、Margaret Sorenson、Stanley J. Schmidt、William R. Brian、John F. Newton、Kathy A. Tyrrell、Eric Garver、Lee A. Yodis、Marie Chabot-Fletcher、Maritsa Tzimas、Edward F. Webb、John J. Breton、Don E. Griswold

  DOI：10.1021/jm960271d

  日期：1996.1.1

  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.
• 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.