(R)-吡咯烷-2-甲腈三氟醋酸盐 | 1523530-11-1

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: (R)-吡咯烷-2-甲腈三氟醋酸盐
• 英文名称: (2R)-pyrrolidine-2-carbonitrile (TFA salt)
• 英文别名: (R)-2-Cyanopyrrolidine tfa；(2R)-pyrrolidine-2-carbonitrile;2,2,2-trifluoroacetic acid
• CAS: 1523530-11-1
• 化学式: C₂HF₃O₂*C₅H₈N₂
• 分子量: 210.156
• InChiKey: QROMHLFLMYDBEQ-NUBCRITNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  73.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-吡咯烷-2-甲腈三氟醋酸盐 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 sodium methylate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 28.0h， 生成 VPC₉₆₁₁₅
  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
• 作为产物：
  描述：

  (2R)-2-氨甲酰基吡咯烷-1-甲酸叔丁酯 在 2,4,6-三甲基吡啶 、 三聚氯氰 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (R)-吡咯烷-2-甲腈三氟醋酸盐
  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

• Constrained Peptidomimetics Reveal Detailed Geometric Requirements of Covalent Prolyl Oligopeptidase Inhibitors
  作者：Janice Lawandi、Sylvestre Toumieux、Valentine Seyer、Philip Campbell、Sabine Thielges、Lucienne Juillerat-Jeanneret、Nicolas Moitessier

  DOI：10.1021/jm901013a

  日期：2009.11.12

  Prolyl oligopeptidases cleave peptides on the carboxy side of internal proline residues and their inhibition has potential in the treatment of human brain disorders. Using our docking program FITTED, we have designed a series of constrained covalent inhibitors, built from a series of bicyclic scaffolds, to study the optimal shape required for these small molecules. These structures bear nitrile functional groups that we predicted to covalently bind to the catalytic serine of the enzyme. Synthesis and biological assays using human brain-derived astrocytic cells and endothelial cells and human fibroblasts revealed that these compounds act as selective inhibitors of prolyl oligopeptidase activity compared to prolyl-dipeptidyl-aminopeptidase activity, are able to penetrate the cells and inhibit intracellular activities in intact living cells. This integrated computational and experimental study shed light oil the binding mode of inhibitors in the enzyme active site and will guide the design of future drug-like molecules.
• [EN] ULK3 INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS D'ULK3 ET LEURS UTILISATIONS
  申请人：[en]H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：WO2024035771A2

  公开（公告）日：2024-02-15

  The present disclosure provides compounds of Formula (I), Formula (II) and Formula (III) which are useful as inhibitors of ULK3 and methods of using the same to treat cancers, such as ULK-associated cancers, for example multiple myeloma and breast cancer.