2,2,2-trideuterio-1-[1-deuterio-4-[(1R,2S,3R)-1,2,3,4-tetradeuteriooxybutyl]imidazol-2-yl]ethanone | 1258455-15-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,2,2-trideuterio-1-[1-deuterio-4-[(1R,2S,3R)-1,2,3,4-tetradeuteriooxybutyl]imidazol-2-yl]ethanone
• CAS: 1258455-15-0
• 化学式: C₉H₁₄N₂O₅
• 分子量: 238.157
• InChiKey: CQSIXFHVGKMLGQ-DSFGRQTHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  127
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,2,2-trideuterio-1-[1-deuterio-4-[(1R,2S,3R)-1,2,3,4-tetradeuteriooxybutyl]imidazol-2-yl]ethanone 在 盐酸 、 氘代盐酸 作用下， 以 1,4-二氧六环 、 water-d2 、 水 为溶剂， 生成 (1R,2S,3R)-1-[2-[(E)-N-hydroxy-C-(trideuteriomethyl)carbonimidoyl]-1H-imidazol-5-yl]butane-1,2,3,4-tetrol
  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 重水 、 氘代盐酸 作用下， 生成 2,2,2-trideuterio-1-[1-deuterio-4-[(1R,2S,3R)-1,2,3,4-tetradeuteriooxybutyl]imidazol-2-yl]ethanone
  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

• 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.