3-(4-((4S,4'R,5R)-2,2,2',2'-tetramethyl-[4,4'-bi(1,3-dioxolan)]-5-yl)-1H-imidazol-2-yl)isoxazole | 1054544-16-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(4-((4S,4'R,5R)-2,2,2',2'-tetramethyl-[4,4'-bi(1,3-dioxolan)]-5-yl)-1H-imidazol-2-yl)isoxazole
• CAS: 1054544-16-9
• 化学式: C₁₆H₂₁N₃O₅
• 分子量: 335.36
• InChiKey: WRRGPJWRHJGLLX-JHJVBQTASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.41
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  91.63
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3-(4-((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， 以321 mg的产率得到(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
• 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 38.0h， 生成 3-(4-((4S,4'R,5R)-2,2,2',2'-tetramethyl-[4,4'-bi(1,3-dioxolan)]-5-yl)-1H-imidazol-2-yl)isoxazole
  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

• WO2008/109314
  申请人：——

  公开号：——

  公开（公告）日：——