(S)-amino(2-(3-(4-(3-(ethoxymethyl)-5-methylbenzyl)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium chloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-amino(2-(3-(4-(3-(ethoxymethyl)-5-methylbenzyl)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium chloride
• 英文别名: (2S)-2-[3-[4-[[3-(ethoxymethyl)-5-methylphenyl]methyl]phenyl]-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboximidamide;hydrochloride
• 化学式: C₂₄H₂₉N₅O₂*ClH
• 分子量: 455.988
• InChiKey: QAUVBBYBXYSSLN-BOXHHOBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.62
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,5-二(溴甲基)甲苯 在 盐酸 、 四(三苯基膦)钯 、 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 盐酸羟胺 、 sodium hydride 、 sodium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 96.0h， 生成 (S)-amino(2-(3-(4-(3-(ethoxymethyl)-5-methylbenzyl)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium chloride
  参考文献：
  名称：

  Structure–activity relationship studies of the lipophilic tail region of sphingosine kinase 2 inhibitors

  摘要：

  Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of the S1P signaling pathway has attracted significant attention because alteration of S1P levels is linked to several disease states including cancer, fibrosis, and sickle cell disease. While intense investigations have focused on developing SphK1 inhibitors, only a limited number of SphK2-selective agents have been reported. Herein, we report our investigations on the structure-activity relationship studies of the lipophilic tail region of SLR080811, a SphK2-selective inhibitor. Our studies demonstrate that the internal phenyl ring is a key structural feature that is essential in the SLR080811 scaffold. Further, we show the dependence of SphK2 activity and selectivity on alkyl tail length, suggesting a larger lipid binding pocket in SphK2 compared to SphK1. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.03.041

文献信息

• Structure–activity relationship studies of the lipophilic tail region of sphingosine kinase 2 inhibitors
  作者：Molly D. Congdon、Elizabeth S. Childress、Neeraj N. Patwardhan、James Gumkowski、Emily A. Morris、Yugesh Kharel、Kevin R. Lynch、Webster L. Santos

  DOI：10.1016/j.bmcl.2015.03.041

  日期：2015.11

  Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of the S1P signaling pathway has attracted significant attention because alteration of S1P levels is linked to several disease states including cancer, fibrosis, and sickle cell disease. While intense investigations have focused on developing SphK1 inhibitors, only a limited number of SphK2-selective agents have been reported. Herein, we report our investigations on the structure-activity relationship studies of the lipophilic tail region of SLR080811, a SphK2-selective inhibitor. Our studies demonstrate that the internal phenyl ring is a key structural feature that is essential in the SLR080811 scaffold. Further, we show the dependence of SphK2 activity and selectivity on alkyl tail length, suggesting a larger lipid binding pocket in SphK2 compared to SphK1. (C) 2015 Elsevier Ltd. All rights reserved.