1-methyl-1-{2-(4-(4-pentyl-1H-1,2,3-triazol-1-yl)phenyl)ethyl}piperidin-1-ium methanesulfonate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-methyl-1-{2-(4-(4-pentyl-1H-1,2,3-triazol-1-yl)phenyl)ethyl}piperidin-1-ium methanesulfonate
• 英文别名: 1-(4-(4-pentyl-1H-1,2,3-triazol-1-yl)phenethyl)-1-methylpiperidinium methanesulfonate；Methanesulfonate;1-methyl-1-[2-[4-(4-pentyltriazol-1-yl)phenyl]ethyl]piperidin-1-ium；methanesulfonate;1-methyl-1-[2-[4-(4-pentyltriazol-1-yl)phenyl]ethyl]piperidin-1-ium
• 化学式: CH₃O₃S*C₂₁H₃₃N₄
• 分子量: 436.619
• InChiKey: YLJOZPGEGYALPV-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.33
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  96.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氨基苯乙醇 在 盐酸 、 copper(II) sulfate 、 sodium ascorbate 、 三乙胺 、 sodium nitrite 作用下， 以 二氯甲烷 、 水 、 乙腈 、 叔丁醇 为溶剂， 反应 66.5h， 生成 1-methyl-1-{2-(4-(4-pentyl-1H-1,2,3-triazol-1-yl)phenyl)ethyl}piperidin-1-ium methanesulfonate
  参考文献：
  名称：

  Structure–Activity Relationships and Molecular Modeling of Sphingosine Kinase Inhibitors

  摘要：

  The design, synthesis, and evaluation of the potency of new isoform-selective inhibitors of sphingosine kinases I and 2 (SK1 and SK2), the enzyme that catalyzes the phosphorylation of D-erythro-sphingosine to produce the key signaling lipid, sphingosine 1-phosphate, are described. Recently, we reported that 1-(4-octylphenethyl)piperidin-4-ol (RB-005) is a selective inhibitor of SK1. Here we report the synthesis of 43 new analogues of RB-005, in which the lipophilic tail, polar headgroup, and linker region were modified to extend the structure-activity relationship profile for this lead compound, which we explain using modeling studies with the recently published crystal structure of SKI. We provide a basis for the key residues targeted by our profiled series and provide further evidence for the ability to discriminate between the two isoforms using pharmacological intervention.

  DOI：

  10.1021/jm401399c

文献信息

• [EN] SELECTIVE INHIBITORS AND ALLOSTERIC ACTIVATORS OF SPHINGOSINE KINASE<br/>[FR] INHIBITEURS SÉLECTIFS ET ACTIVATEURS ALLOSTÉRIQUES DE LA SPHINGOSINE KINASE
  申请人：UNIV CITY NEW YORK RES FOUND

  公开号：WO2014118556A2

  公开（公告）日：2014-08-07

  Sphingosine 1-phosphate (S1P) is involved in hyper-proliferative diseases, such as cancer and vascular remodeling in pulmonary arterial hypertension. Inhibitors of sphingosine kinase 1 and 2 (SK1 and SK2), which catalyze the synthesis of S1P, may be useful anti- proliferative agents. We have synthesized a series of sphingosine-based inhibitors of SK and SK2. Also provided in this invention are compounds that activate SK1 which can be used in diseases such as fibrosis, where intracellular S1P is anti-fibrotic.
• Structure–Activity Relationships and Molecular Modeling of Sphingosine Kinase Inhibitors
  作者：Dong Jae Baek、Neil MacRitchie、Nahoum G. Anthony、Simon P. Mackay、Susan Pyne、Nigel J. Pyne、Robert Bittman

  DOI：10.1021/jm401399c

  日期：2013.11.27

  The design, synthesis, and evaluation of the potency of new isoform-selective inhibitors of sphingosine kinases I and 2 (SK1 and SK2), the enzyme that catalyzes the phosphorylation of D-erythro-sphingosine to produce the key signaling lipid, sphingosine 1-phosphate, are described. Recently, we reported that 1-(4-octylphenethyl)piperidin-4-ol (RB-005) is a selective inhibitor of SK1. Here we report the synthesis of 43 new analogues of RB-005, in which the lipophilic tail, polar headgroup, and linker region were modified to extend the structure-activity relationship profile for this lead compound, which we explain using modeling studies with the recently published crystal structure of SKI. We provide a basis for the key residues targeted by our profiled series and provide further evidence for the ability to discriminate between the two isoforms using pharmacological intervention.