2-ethyl-4-n-butyl-1,2,4-thiadiazolidine-3,5-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-ethyl-4-n-butyl-1,2,4-thiadiazolidine-3,5-dione
• 英文别名: 2-ethyl-4-butyl-1,2,4-thiadiazolidine-3,5-dione；4-Butyl-2-ethyl-1,2,4-thiadiazolidine-3,5-dione
• 化学式: C₈H₁₄N₂O₂S
• 分子量: 202.277
• InChiKey: WTFFYZGCISALRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  65.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-butyl-carbonochloridimidic hypochlorous thioanhydride 、 异氰酸乙酯 在 air 作用下， 以 正己烷 为溶剂， 反应 8.0h， 生成 2-ethyl-4-n-butyl-1,2,4-thiadiazolidine-3,5-dione
  参考文献：
  名称：

  First Non-ATP Competitive Glycogen Synthase Kinase 3 β (GSK-3β) Inhibitors:  Thiadiazolidinones (TDZD) as Potential Drugs for the Treatment of Alzheimer's Disease

  摘要：

  Glycogen synthase kinase 3beta (GSK-3beta) has a central role in Alzheimer's disease (AD). Selective inhibitors which avoid tau hyperphosphorylation may represent an effective therapeutical approach to the AD pharmacotherapy and other neurodegenerative disorders. Here, we describe the synthesis, biological evaluation, and SAR of the small heterocyclic thiadiazolidinones (TDZD) as the first non-ATP competitive inhibitor of GSK-3beta. Their synthesis is based on the reactivity of sulfenyl chlorides. In GSK-3beta assays, TDZD derivatives showed IC50 values in the micromolar range, whereas in other protein kinases assays they were devoid of any inhibitory activity. SAR studies allowed the identification of the key structural features. Finally, a possible enzymatic binding mode is proposed.

  DOI：

  10.1021/jm011020u

文献信息

• SMALL MOLECULE INHIBITORS OF RGS PROTEINS
  申请人：Neubig Richard

  公开号：US20120277273A1

  公开（公告）日：2012-11-01

  The invention relates to compositions having RGS (regulator of G-protein Signaling) inhibiting activity, and methods of use thereof. In some embodiments, RGS-inhibiting compositions find use in research on or treatment of disease states (e.g., diabetes, epilepsy, neuropathic pain, depression and other diseases).

  该发明涉及具有RGS（G蛋白信号调节因子）抑制活性的组合物，以及其使用方法。在某些实施例中，具有RGS抑制活性的组合物可用于研究或治疗疾病状态（例如糖尿病、癫痫、神经痛、抑郁症和其他疾病）。
• Small Molecule Inhibitors of Regulators of G Protein Signaling (RGS) Proteins
  作者：Emma M. Turner、Levi L. Blazer、Richard R. Neubig、Stephen M. Husbands

  DOI：10.1021/ml200263y

  日期：2012.2.9

  Recently, regulators of G protein signaling (RGS) proteins have emerged as potential therapeutic targets since they provide an alternative method of modulating the activity of G protein-coupled receptors, the target of so many drugs. Inhibitors of RGS proteins must block a protein protein interaction (RGS-G alpha) but also be cell and, depending on the therapeutic target, blood brain barrier permeable. A lead compound (la) was identified as an inhibitor of RGS4 in a screening assay, and this has now been optimized for activity, selectivity, and solubility. The newly developed ligands (11b and 13) display substantial selectivity over the closely related RGS8 protein, lack the off-target calcium mobilization activity of the lead la, and have excellent aqueous solubility. They are currently being evaluated in vivo in rodent models of depression.
• US8865750B2
  申请人：——

  公开号：US8865750B2

  公开（公告）日：2014-10-21
• [EN] SMALL MOLECULE INHIBITORS OF RGS PROTEINS<br/>[FR] INHIBITEURS DE PETITES MOLÉCULES DE PROTÉINES RGS
  申请人：NEUBIG RICHARD

  公开号：WO2012149335A2

  公开（公告）日：2012-11-01

  The invention relates to compositions having RGS (regulator of G-protein Signaling) inhibiting activity, and methods of use thereof. In some embodiments, RGS-inhibiting compositions find use in research on or treatment of disease states (e.g., diabetes, epilepsy, neuropathic pain, depression and other diseases).