N-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)hydroxylamine | 139149-05-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: N-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)hydroxylamine
• CAS: 139149-05-6
• 化学式: C₁₁H₁₅NO₂
• 分子量: 193.246
• InChiKey: WWZARLGTOIDJNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  41.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)hydroxylamine 以 乙醚 、 苯 为溶剂， 生成 N-tert-Butyl-N-(6-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-hydroxylamine
  参考文献：
  名称：

  通过将格氏试剂添加到酮硝酮中来合成受阻仲胺

  摘要：

  格氏试剂在非极性溶剂中加到酮硝酮中，以良好的收率和极少的质子转移竞争性获得N，N-二烷基羟胺。然后用二硫化碳对粗羟胺进行脱氧，从而完成了一条有效的通用合成路线，可生成受阻的仲烷基叔烷基胺和二叔烷基胺。

  DOI：

  10.1016/s0040-4039(00)91707-6
• 作为产物：
  描述：

  6-甲氧基-1-四l酮肟 在 盐酸 、 吡啶硼烷 作用下， 生成 N-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)hydroxylamine
  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

• 5-LIPOXYGENASE INHIBITORS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0522000A1

  公开（公告）日：1993-01-13
• [EN] 5-LIPOXYGENASE INHIBITORS
  申请人：——

  公开号：WO1991014674A2

  公开（公告）日：1991-10-03

  [EN] Hydroxyurea compounds comprising substituted and unsubstituted 1,2,3,4-tetrahydronaphthalene, indane, dihydrobenzofuran, 4H-2,3-dihydrobenzopyran, dihydrobenzothiophene, and indoline derivatives, pharmaceutical compositions containing said compounds, and their use as analgesics and 5-lipoxygenase pathway inhibitors.
  [FR] On décrit des composés d'hydroxyurée comprenant de l'indane, du dihydrobenzofuranne, du 4H-2,3-dihydrobenzopyranne, du dihydrobenzothiophène, des dérivés d'indole et du 1,2,3,4-tétrahydronaphtalène substitués et non substitués, des compositions pharmaceutiques contenant lesdits composés et leur utilisation comme analgésiques et inhibiteurs de voies d'accès de 5-lipoxygénase.
• 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.
• Synthesis of hindered secondary amines via Grignard reagent addition to ketonitrones
  作者：Martin A. Schwartz、Xiufeng Hu

  DOI：10.1016/s0040-4039(00)91707-6

  日期：1992.3

  Grignard reagents add to ketonitrones in a nonpolar solvent to afford N,N-dialkylhydroxylamines in good yields and with little competing proton transfer. Deoxygenation of the crude hydroxylamines with carbon disulfide then completes an efficient general synthetic route to hindered sec-alkyl-tert-alkylamines and to di-tert-alkylamines.

  格氏试剂在非极性溶剂中加到酮硝酮中，以良好的收率和极少的质子转移竞争性获得N，N-二烷基羟胺。然后用二硫化碳对粗羟胺进行脱氧，从而完成了一条有效的通用合成路线，可生成受阻的仲烷基叔烷基胺和二叔烷基胺。