(1R,2S,3R)-1-(2-(1-苄基-1H-1,2,4-三唑-3-基)-1H-咪唑-4-基)丁烷-1,2,3,4-四醇 | 1055027-49-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (1R,2S,3R)-1-(2-(1-苄基-1H-1,2,4-三唑-3-基)-1H-咪唑-4-基)丁烷-1,2,3,4-四醇
• 英文名称: (1R,2S,3R)-1-(2-(1-benzyl-1H-1,2,4-triazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol
• 英文别名: (1R,2S,3R)-1-[2-(1-benzyl-1,2,4-triazol-3-yl)-1H-imidazol-5-yl]butane-1,2,3,4-tetrol
• CAS: 1055027-49-0
• 化学式: C₁₆H₁₉N₅O₄
• 分子量: 345.358
• InChiKey: BBNRKROQKWHULU-MGPQQGTHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  140
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1R,2S,3R)-1-(2-(1-苄基-1H-1,2,4-三唑-3-基)-1H-咪唑-4-基)丁烷-1,2,3,4-四醇 在 盐酸 、 Pearlman catalyst 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 18.0h， 以100%的产率得到(1R,2S,3R)-1-(2-(1H-1,2,4-triazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol
  参考文献：
  名称：

  Inhibition of Sphingosine-1-Phosphate Lyase for the Treatment of Autoimmune Disorders

  摘要：

  During nearly a decade of research dedicated to the study of sphingosine signaling pathways, we identified sphingosine-1-phosphate lyase (S1PL) as a drug target for the treatment of autoimmune disorders. S1PL catalyzes the irreversible decomposition of sphingosine-1-phosphate (S1P) by a retro-aldol fragmentation that yields hexadecanaldehyde and phosphoethanolamine. Genetic models demonstrated that mice expressing reduced S1PL activity had decreased numbers of circulating lymphocytes due to altered lymphocyte trafficking, which prevented disease development in multiple models of autoimmune disease. Mechanistic studies of lymphoid tissue following oral administration of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)-imidazole (THI) 3 showed a clear relationship between reduced lyase activity, elevated S I P levels, and lower levels of circulating lymphocytes. Our internal medicinal chemistry efforts discovered potent analogues of 3 bearing heterocycles as chemical equivalents of the pendant carbonyl present in the parent structure. Reduction of S1PL activity by oral administration of these analogues recapitulated the phenotype of mice with genetically reduced S1PL expression.

  DOI：

  10.1021/jm900278w
• 作为产物：
  描述：

  1-benzyl-1H-1,2,4-triazole-3-cyanide 、 1-氨基-1-脱氧-D-果糖乙酸盐 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 7.0h， 以81%的产率得到(1R,2S,3R)-1-(2-(1-苄基-1H-1,2,4-三唑-3-基)-1H-咪唑-4-基)丁烷-1,2,3,4-四醇
  参考文献：
  名称：

  Inhibition of Sphingosine-1-Phosphate Lyase for the Treatment of Autoimmune Disorders

  摘要：

  During nearly a decade of research dedicated to the study of sphingosine signaling pathways, we identified sphingosine-1-phosphate lyase (S1PL) as a drug target for the treatment of autoimmune disorders. S1PL catalyzes the irreversible decomposition of sphingosine-1-phosphate (S1P) by a retro-aldol fragmentation that yields hexadecanaldehyde and phosphoethanolamine. Genetic models demonstrated that mice expressing reduced S1PL activity had decreased numbers of circulating lymphocytes due to altered lymphocyte trafficking, which prevented disease development in multiple models of autoimmune disease. Mechanistic studies of lymphoid tissue following oral administration of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)-imidazole (THI) 3 showed a clear relationship between reduced lyase activity, elevated S I P levels, and lower levels of circulating lymphocytes. Our internal medicinal chemistry efforts discovered potent analogues of 3 bearing heterocycles as chemical equivalents of the pendant carbonyl present in the parent structure. Reduction of S1PL activity by oral administration of these analogues recapitulated the phenotype of mice with genetically reduced S1PL expression.

  DOI：

  10.1021/jm900278w

文献信息

• S1P LYASE INHIBITORS FOR THE TREATMENT OF CEREBRAL MALARIA
  申请人：Brown Philip Manton

  公开号：US20100113530A1

  公开（公告）日：2010-05-06

  Methods and compositions for treating, managing, and/or preventing cerebral malaria are disclosed.

  揭示了用于治疗、管理和/或预防脑疟疾的方法和组合物。
• COMBINATIONS COMPRISING BICYCLIC S1P LYASE INHIBITORS
  申请人：Oravecz Tamas

  公开号：US20100048649A1

  公开（公告）日：2010-02-25

  Methods and compositions for treating immunological and inflammatory diseases and disorders are disclosed. Particular methods and compositions comprise the administration of an agent that inhibits S1P lyase activity and at least one additional immunosuppressive and/or anti-inflammatory agent.

  本发明涉及用于治疗免疫和炎症性疾病和紊乱的方法和组合物。具体方法和组合物包括给予一种抑制S1P裂解酶活性的药物以及至少一种额外的免疫抑制和/或抗炎药物。
• [EN] COMBINATIONS COMPRISING BICYCLIC S1P LYASE INHIBITORS<br/>[FR] COMBINAISONS COMPRENANT DES INHIBITEURS DE S1P LYASE BICYCLIQUES
  申请人：LEXICON PHARMACEUTICALS INC

  公开号：WO2010022217A1

  公开（公告）日：2010-02-25

  Methods and compositions for treating immunological and inflammatory diseases and disorders are disclosed. Particular methods and compositions comprise the administration of an agent that inhibits S1P lyase activity and at least one additional immunosuppressive and/or anti-inflammatory agent.

  本发明揭示了用于治疗免疫和炎症性疾病和疾患的方法和组合物。特定的方法和组合物包括给予一种抑制S1P裂解酶活性的药物和至少一种额外的免疫抑制和/或抗炎药物的治疗。
• [EN] S1P LYASE INHIBITORS FOR THE TREATMENT OF CEREBRAL MALARIA<br/>[FR] INHIBITEURS DE LA S1P LYASE DESTINÉS AU TRAITEMENT DU PALUDISME CÉRÉBRAL
  申请人：LEXICON PHARMACEUTICALS INC

  公开号：WO2010051353A1

  公开（公告）日：2010-05-06

  Methods and compositions for treating, managing, and/or preventing cerebral malaria are disclosed.

  本发明揭示了用于治疗、管理和/或预防脑型疟疾的方法和组合物。
• WO2008/109314
  申请人：——

  公开号：——

  公开（公告）日：——