(1R,2S,3R)-1-(2-(异噁唑-3-基)-1H-咪唑-4-基)丁烷-1,2,3,4-四醇 | 1055027-48-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (1R,2S,3R)-1-(2-(异噁唑-3-基)-1H-咪唑-4-基)丁烷-1,2,3,4-四醇
• 英文名称: (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol
• 英文别名: LX2932；(1R,2S,3R)-1-(2-(Isoxazol-3-yl)-1H-imidazol-5-yl)butane-1,2,3,4-tetraol；(1R,2S,3R)-1-[2-(1,2-oxazol-3-yl)-1H-imidazol-5-yl]butane-1,2,3,4-tetrol
• CAS: 1055027-48-9
• 化学式: C₁₀H₁₃N₃O₅
• 分子量: 255.23
• InChiKey: WGDPRIZUIYIENM-IWSPIJDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  136
• 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-(异噁唑-3-基)-1H-咪唑-4-基)丁烷-1,2,3,4-四醇 在 sodium tetrahydroborate 、 sodium periodate 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 生成 (2-(isoxazol-3-yl)-1H-imidazol-4-yl)methanol
  参考文献：
  名称：

  [EN] COMPOUNDS AND USE THEREOF FOR THE TREATMENT OF INFECTIOUS DISEASES AND CANCER
  [FR] COMPOSÉS ET LEUR UTILISATION POUR LE TRAITEMENT DE MALADIES INFECTIEUSES ET DU CANCER

  摘要：

  该发明提供了咪唑、噁唑和噻唑化合物及其在治疗疾病或障碍的方法中的应用，例如感染性疾病和癌症，其中抑制神经鞘氨醇-1-磷酸裂解酶对治疗疾病或障碍是有益的。

  公开号：

  WO2021032857A1
• 作为产物：
  描述：

  1-[4-(1,2,3,4-四羟基丁基)-1H-咪唑-2-基]乙酮 在 盐酸 、 正丁基锂 、 水 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 1,1-二氯乙烷 、 正己烷 为溶剂， 反应 40.0h， 生成 (1R,2S,3R)-1-(2-(异噁唑-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 Rheumatoid Arthritis: Discovery of (E)-1-(4-((1R,2S,3R)-1,2,3,4-Tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone Oxime (LX2931) and (1R,2S,3R)-1-(2-(Isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol (LX2932)

  摘要：

  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.

  DOI：

  10.1021/jm101183p

文献信息

• METHODS OF PREPARING IMIDAZOLE-BASED BICYCLIC COMPOUNDS
  申请人：Guohua Jason

  公开号：US20090318705A1

  公开（公告）日：2009-12-24

  Methods of preparing compounds of formula I are disclosed:

  公开了制备式I化合物的方法：
• SOLID FORMS OF (1R,2S,3R)-1-(2-(ISOXAZOL-3-YL)-1H-IMIDAZOL-4-YL)BUTANE-1,2,3,4-TETRAOL AND METHODS OF THEIR USE
  申请人：Burgoon Hugh Alfred

  公开号：US20090318516A1

  公开（公告）日：2009-12-24

  Solid forms of (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol and hydrates thereof are disclosed, as well as compositions comprising them and methods of their use.

  固体形式的(1R,2S,3R)-1-(2-(异噁唑-3-基)-1H-咪唑-4-基)丁烷-1,2,3,4-四醇及其水合物被披露，以及包含它们的组合物和使用方法。
• 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。