(1R,2S,3R)-1-(2-(5-methylisoxazol-3-yl)-1H-imidazol-5-yl)butane-1,2,3,4-tetraol | 1054543-28-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1R,2S,3R)-1-(2-(5-methylisoxazol-3-yl)-1H-imidazol-5-yl)butane-1,2,3,4-tetraol
• 英文别名: (1R,2S,3R)-1-[2-(5-methyl-1,2-oxazol-3-yl)-1H-imidazol-5-yl]butane-1,2,3,4-tetrol
• CAS: 1054543-28-0
• 化学式: C₁₁H₁₅N₃O₅
• 分子量: 269.257
• InChiKey: LHFBKICTCYKWTR-OPRDCNLKSA-N

物化性质

• 沸点：
  713.6±60.0 °C(predicted)
• 密度：
  1.530±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  136
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-methyl-3-(5-((4S,4'R,5R)-2,2,2',2'-tetramethyl-[4,4'-bi(1,3-dioxolan)]-5-yl)-1H-imidazol-2-yl)isoxazole 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 (1R,2S,3R)-1-(2-(5-methylisoxazol-3-yl)-1H-imidazol-5-yl)butane-1,2,3,4-tetraol
  参考文献：
  名称：

  WO2008/109314

  摘要：

  公开号：

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。
• Inhibition of Sphingosine 1-Phosphate Lyase for the Treatment of Rheumatoid Arthritis: Discovery of (<i>E</i>)-1-(4-((1<i>R</i>,2<i>S</i>,3<i>R</i>)-1,2,3,4-Tetrahydroxybutyl)-1<i>H</i>-imidazol-2-yl)ethanone Oxime (LX2931) and (1<i>R</i>,2<i>S</i>,3<i>R</i>)-1-(2-(Isoxazol-3-yl)-1<i>H</i>-imidazol-4-yl)butane-1,2,3,4-tetraol (LX2932)
  作者：Jeffrey T. Bagdanoff、Michael S. Donoviel、Amr Nouraldeen、Marianne Carlsen、Theodore C. Jessop、James Tarver、Saadat Aleem、Li Dong、Haiming Zhang、Lakmal Boteju、Jill Hazelwood、Jack Yan、Mark Bednarz、Suman Layek、Iris B. Owusu、Suma Gopinathan、Liam Moran、Zhong Lai、Jeff Kramer、S. David Kimball、Padmaja Yalamanchili、William E. Heydorn、Kenny S. Frazier、Barbara Brooks、Philip Brown、Alan Wilson、William K. Sonnenburg、Alan Main、Kenneth G. Carson、Tamas Oravecz、David J. Augeri

  DOI：10.1021/jm101183p

  日期：2010.12.23

  Sphingosine 1-phosphate lyase (S1PL) has been characterized as a novel target for the treatment of autoimmune disorders using genetic and pharmacological methods. Medicinal chemistry efforts targeting S1PL by direct in vivo evaluation of synthetic analogues of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxy-butyl)-imidazole (THI, 1) led to the discovery of 2 (LX2931) and 4 (LX2932). The immunological phenotypes observed in S1PL deficient mice were recapitulated by oral administration of 2 or 4. Oral dosing of 2 or 4 yielded a dose-dependent decrease in circulating lymphocyte numbers in multiple species and showed a therapeutic effect in rodent models of rheumatoid arthritis (RA). Phase I clinical trials indicated that 2, the first clinically studied inhibitor of S1PL, produced a dose-dependent and reversible reduction of circulating lymphocytes and was well tolerated at dose levels of up to 180 mg daily. Phase II evaluation of 2 in patients with active rheumatoid arthritis is currently underway.