(1R,2S,3R)-1-(2-(4,5-dihydroisoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol | 1258454-93-1

• 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-(4,5-dihydroisoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol
• 英文别名: (1R,2S,3R)-1-(2-(4,5-dihydroisoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetrol；(1R,2S,3R)-1-[2-(4,5-dihydro-1,2-oxazol-3-yl)-1H-imidazol-5-yl]butane-1,2,3,4-tetrol
• CAS: 1258454-93-1
• 化学式: C₁₀H₁₅N₃O₅
• 分子量: 257.246
• InChiKey: QDTDZQQOVFFOMY-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：
  0.6
• 拓扑面积：
  131
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 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 、 水 为溶剂， 反应 25.25h， 生成 (1R,2S,3R)-1-(2-(4,5-dihydroisoxazol-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

文献信息

• ENHANCEMENT OF CHEMOTHERAPY EFFICIENCY BY SPHINGOSINE-1-PHOSPHATE
  申请人：AC BioScience

  公开号：EP3443986A1

  公开（公告）日：2019-02-20

  The present invention relates to neoadjuvant prior to chemotherapy. The present invention relates to sphingosine-1-phosphate pathway activator for use in the treatment of cancer as neoadjuvant prior to chemotherapy selected from sphingosine-1-phosphate, sphingosine-1-phosphate lyase inhibitor, sphingosine-1-phospahte receptor agonist and sphingosine kinase activator. The sphingosine-1-phosphate pathway activator enhances the chemotherapy efficiency through the normalization of intratumoral vascular network, promoting the effects of the sequential administration of an anticancer agent.

  本发明涉及化疗前的新辅助治疗。 本发明涉及选自鞘磷脂-1-磷酸、鞘磷脂-1-磷酸裂解酶抑制剂、鞘磷脂-1-磷酸受体激动剂和鞘磷脂激酶激活剂的用于治疗癌症的鞘磷脂-1-磷酸途径激活剂，作为化疗前的新辅助剂。 鞘氨醇-1-磷酸途径激活剂通过使瘤内血管网络正常化来提高化疗效率，促进抗癌剂连续给药的效果。
• ENHANCEMENT OF CANCER TREATMENT EFFICIENCY VIA THE SPHINGOSINE-1-PHOSPHATE PATHWAY
  申请人：AC BIOSCIENCE

  公开号：US20200261420A1

  公开（公告）日：2020-08-20

  The use of a neoadjuvant prior to chemotherapy. A sphingosine-1-phosphate pathway activator for use in the treatment of cancer as a neoadjuvant prior to chemotherapy selected from sphingosine-1-phosphate lyase inhibitors. The sphingosine-1-phosphate pathway activator enhances the chemotherapy efficiency through the normalization of intratumoral vascular network, promoting the effects of the sequential administration of an anticancer agent or a sequential radiotherapy.
• 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.