5-((dimethylamino)methyl)isoxazole-3-carbonitrile | 1258455-10-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-((dimethylamino)methyl)isoxazole-3-carbonitrile
• CAS: 1258455-10-5
• 化学式: C₇H₉N₃O
• 分子量: 151.168
• InChiKey: CDJUOHIQECKKTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.61
• 重原子数：
  11.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  53.06
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  5-((dimethylamino)methyl)isoxazole-3-carbonitrile 、 (3S,4S,5R)-2-(aminomethyl)-5-(hydroxymethyl)tetrahydrofuran-2,3,4-triol 在 sodium methylate 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 43.0h， 生成 (1R,2S,3R)-1-(2-(5-((dimethylamino)methyl)isoxazol-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 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