N-Hydroxy-N-(5-benzyloxyindan-1-yl)urea | 138936-59-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: N-Hydroxy-N-(5-benzyloxyindan-1-yl)urea
• 英文别名: (+/-)-N-hydroxy-N-[2,3-dihydro-5-(benzyloxy)-1H-inden-1-yl]urea；N-Hydroxy-N-[2,3-dihydro-5-(benzyloxy)-1H-inden-1yl]urea；1-hydroxy-1-(5-phenylmethoxy-2,3-dihydro-1H-inden-1-yl)urea
• CAS: 138936-59-1；184575-21-1；184575-22-2
• 化学式: C₁₇H₁₈N₂O₃
• 分子量: 298.342
• InChiKey: IBMSXHGYLKLCAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  75.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-Hydroxy-N-(5-benzyloxyindan-1-yl)urea 生成 (+)-N-hydroxy-N-[2,3-dihydro-5-(benzyloxy)-1H-inden-1-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
• 作为产物：
  描述：

  5-Benzyloxy-indan-1-one oxime 在 盐酸 、 吡啶硼烷 作用下， 以 四氢呋喃 为溶剂， 生成 N-Hydroxy-N-(5-benzyloxyindan-1-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

• 5-LIPOXYGENASE INHIBITORS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0522000A1

  公开（公告）日：1993-01-13
• US5256789A
  申请人：——

  公开号：US5256789A

  公开（公告）日：1993-10-26
• [EN] ANTIINFLAMMATORY HYDROXAMIC ACIDS AND N-HYDROXYUREAS
  申请人：PFIZER INC

  公开号：WO1991016298A1

  公开（公告）日：1991-10-31

  (EN) Compounds having structure (I) wherein X is nitrogen, oxygen, sulfur or a bond and Z is oxygen or sulfur have been synthesized. These compounds are lipoxygenase inhibitors and are useful as the active agent in pharmaceutical compositions for treating inflammatory conditions in humans and other mammals for which lipoxygenase activity has been implicated.(FR) On a produit par synthèse des composés ayant la structure (I) où X représente azote, oxygène, soufre ou une liaison et Z représente oxygène ou soufre. Ces composés sont des inhibiteurs de lipoxygénase et sont utiles comme agent actif dans des compositions pharmaceutiques visant à traiter des états inflammatoires chez l'homme et chez d'autres mammifères, états dans lesquels une activité de lypoxygénase est impliquée.
• [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.
• [EN] 5-LIPOXYGENASE INHIBITORS<br/>[FR] INHIBITEURS DE LA 5-LIPOXYGENASE
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：WO1995002575A1

  公开（公告）日：1995-01-26

  (EN) Hydroxyurea compounds comprising halo substituted 1, 2, 3, 4-tetrahydronaphthalene, and indane derivatives, pharmaceutical compositions and their use as OPUFA and 5-lipoxygenase pathway inhibitors.(FR) Composés d'hydroxyurée comprenant du 1, 2, 3, 4-tétrahydronaphtalène à substitution halo, dérivés d'indane, compositions pharmaceutiques et leur utilisation en tant qu'inhibiteurs d'acides gras polyinsaturés oxygénés et de la voie de la 5-lipoxygénase.