(S)-1-(4-(4-(3-(2-cyclohexylethyl)phenyl)-1H-imidazol-2-yl)benzoyl)pyrrolidine-2-carboximidamide hydrochloride | 1307310-07-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-1-(4-(4-(3-(2-cyclohexylethyl)phenyl)-1H-imidazol-2-yl)benzoyl)pyrrolidine-2-carboximidamide hydrochloride
• 英文别名: (2S)-1-[4-[5-[3-(2-cyclohexylethyl)phenyl]-1H-imidazol-2-yl]benzoyl]pyrrolidine-2-carboximidamide;hydrochloride
• CAS: 1307310-07-1
• 化学式: C₂₉H₃₅N₅O*ClH
• 分子量: 506.091
• InChiKey: ZPYNQFSHGHZMAL-SNYZSRNZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.22
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  98.9
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-(叔丁氧羰基)苯甲 酸 在 ammonium acetate 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 sodium methylate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 、 二氯甲烷 为溶剂， 反应 47.6h， 生成 (S)-1-(4-(4-(3-(2-cyclohexylethyl)phenyl)-1H-imidazol-2-yl)benzoyl)pyrrolidine-2-carboximidamide hydrochloride
  参考文献：
  名称：

  Development of Amidine-Based Sphingosine Kinase 1 Nanomolar Inhibitors and Reduction of Sphingosine 1-Phosphate in Human Leukemia Cells

  摘要：

  Sphingosine 1-phosphate (S1P) is a bioactive lipid that has been identified as an accelerant of cancer progression. The sphingosine kinases (SphKs) are the sole producers of S1P, and thus, SphK inhibitors may prove effective in cancer mitigation and chemosensitization. Of the two SphKs, SphK1 overexpression has been observed in a myriad of cancer cell lines and tissues and has been recognized as the presumptive target over that of the poorly characterized SphK2. Herein, we present the design and synthesis of amidine-based nanomolar SphK1 subtype-selective inhibitors. A homology model of SphK1, trained with this library of amidine inhibitors, was then used to predict the activity of additional, more potent, inhibitors. Lastly, select amidine inhibitors were validated in human leukemia U937 cells, where they significantly reduced endogenous S1P levels at nanomolar concentrations.

  DOI：

  10.1021/jm2001053

文献信息

• Development of Amidine-Based Sphingosine Kinase 1 Nanomolar Inhibitors and Reduction of Sphingosine 1-Phosphate in Human Leukemia Cells
  作者：Andrew J. Kennedy、Thomas P. Mathews、Yugesh Kharel、Saundra D. Field、Morgan L. Moyer、James E. East、Joseph D. Houck、Kevin R. Lynch、Timothy L. Macdonald

  DOI：10.1021/jm2001053

  日期：2011.5.26

  Sphingosine 1-phosphate (S1P) is a bioactive lipid that has been identified as an accelerant of cancer progression. The sphingosine kinases (SphKs) are the sole producers of S1P, and thus, SphK inhibitors may prove effective in cancer mitigation and chemosensitization. Of the two SphKs, SphK1 overexpression has been observed in a myriad of cancer cell lines and tissues and has been recognized as the presumptive target over that of the poorly characterized SphK2. Herein, we present the design and synthesis of amidine-based nanomolar SphK1 subtype-selective inhibitors. A homology model of SphK1, trained with this library of amidine inhibitors, was then used to predict the activity of additional, more potent, inhibitors. Lastly, select amidine inhibitors were validated in human leukemia U937 cells, where they significantly reduced endogenous S1P levels at nanomolar concentrations.