2,4-dibenzyl-1,2,4-thiadiazolidine-3,5-dione

• 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: 2,4-dibenzyl-1,2,4-thiadiazolidine-3,5-dione
• 化学式: C₁₆H₁₄N₂O₂S
• 分子量: 298.365
• InChiKey: SGSVNPJHIDULGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 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：

  C₁₆H₁₄Cl₂N₂OS 在 air 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 2,4-dibenzyl-1,2,4-thiadiazolidine-3,5-dione
  参考文献：
  名称：

  Tideglusib and Its Analogues As Inhibitors of Staphylococcus aureus SrtA

  摘要：

  Sortase A (SrtA) anchors surface proteins to the cell wall envelope, and it has attracted increasing interesting as a potential antivirulence target. Several small-molecule inhibitors for SrtA have been developed, but target validation remains largely underexplored. Herein, we report a new class of SrtA inhibitors that supports antivirulence therapy through small-molecule targeting of SrtA. Tideglusib (TD), a drug candidate for myotonic dystrophy, was outstanding in high-throughput screening. A concise synthetic route quickly provided TD analogues, and the structure-activity relationships for SrtA inhibition have been established from those analogues. Several compounds largely retained the in vitro potency and exhibited a better solubility than TD. Additionally, TD attenuated virulence-related phenotypes in vitro and protected mice against lethal S. aureus USA300 bacteremia. Our study indicates that TD and its analogues could be new candidates as SrtA inhibitors with potential in the development of new antivirulence agents.

  DOI：

  10.1021/acs.jmedchem.0c00803

文献信息

• Thiadiazolidinones as GSK-3 inhibitors
  申请人：Neuropharma S.A.U.

  公开号：EP1586318A1

  公开（公告）日：2005-10-19

  Provided are compounds of formula I wherein R1 is an organic group having at least 8 atoms selected from C or O which is not linked directly to the N through a -C(O)- and their pharmaceutical compositions. These compounds are selective GSK-3 inhibitors and have improved bioavailability. They are useful for the treatment of GSK-3 mediated diseases, among others Alzheimer's disease and type II diabetes.

  提供的是具有公式I的化合物，其中R1是一个有至少8个来自C或O的原子的有机基团，该基团不通过-C(O)-直接连接到N，并且它们的药物组成。这些化合物是选择性GSK-3抑制剂，并具有改善的生物利用度。它们可用于治疗GSK-3介导的疾病，包括阿尔茨海默病和2型糖尿病等其他疾病。
• [EN] THIADIAZOLIDINONES AS GSK-3 INHIBITORS<br/>[FR] THIADIAZOLIDINONES EN TANT QU'INHIBITEURS DE LA GSK-3
  申请人：NEUROPHARMA SA

  公开号：WO2005097117A1

  公开（公告）日：2005-10-20

  Provided are thiadiazolidine compounds of Formula (I) wherein R1 is an organic group having at least 8 atoms selected from C or O, which is not linked directly to the N through a -C(O)- and comprising at least an aromatic ring, and their pharmaceutical compositions. These compounds are selective GSK-3 inhibitors and have improved bioavailability. They are useful for the treatment of GSK-3 mediated diseases, among others Alzheimer's disease, type II diabetes, depression and brain injury.

  提供的是式（I）的噻二唑烷化合物，其中R1是有机基团，至少有8个原子，选择自C或O，不通过-C（O）-直接连接N，并包括至少一个芳香环，以及它们的药物组成物。这些化合物是选择性的GSK-3抑制剂，并具有改善的生物利用度。它们对于治疗GSK-3介导的疾病非常有用，包括阿尔茨海默病、2型糖尿病、抑郁症和脑损伤等。
• GSK-3 inhibitors
  申请人：Padilla Medina Miguel

  公开号：US20050222220A1

  公开（公告）日：2005-10-06

  Provided are thiadiazolidine compounds of formula I wherein R 1 is an organic group having at least 8 atoms selected from C or O, which is not linked directly to the N through a —C(O)— and comprising at least an aromatic ring, and their pharmaceutical compositions. These compounds are selective GSK-3 inhibitors and have improved bioavailability. They are useful for the treatment of GSK-3 mediated diseases, among others Alzheimer's disease, type II diabetes, depression and brain injury.

  提供的是公式I的噻二唑烷化合物，其中R1是有机基团，至少由C或O中选择的8个原子组成，该基团没有直接通过—C(O)—与N相连，并且至少包含一个芳香环，以及它们的药物组成。这些化合物是选择性GSK-3抑制剂，具有改善的生物利用度。它们可用于治疗GSK-3介导的疾病，包括阿尔茨海默病、2型糖尿病、抑郁症和脑损伤等。
• GSK-3 Inhibitors
  申请人：Medina Padilla Miguel

  公开号：US20090233971A1

  公开（公告）日：2009-09-17

  Provided are thiadiazolidine compounds of formula I wherein R 1 is an organic group having at least 8 atoms selected from C or O, which is not linked directly to the N through a —C(O)— and comprising at least an aromatic ring, and their pharmaceutical compositions. These compounds are selective GSK-3 inhibitors and have improved bioavailability. They are useful for the treatment of GSK-3 mediated diseases, among others Alzheimer's disease, type II diabetes, depression and brain injury.

  提供了公式I的噻二唑烷化合物，其中R1是有机基团，至少有8个原子，选择自C或O，不通过-C（O）- 直接与N链接，并且包含至少一个芳香环，以及它们的制药组合物。这些化合物是选择性GSK-3抑制剂，并具有改善的生物利用度。它们对于治疗GSK-3介导的疾病特别是老年痴呆症、2型糖尿病、抑郁症和脑损伤等方面是有用的。
• First Non-ATP Competitive Glycogen Synthase Kinase 3 β (GSK-3β) Inhibitors:  Thiadiazolidinones (TDZD) as Potential Drugs for the Treatment of Alzheimer's Disease
  作者：Ana Martinez、Mercedes Alonso、Ana Castro、Concepción Pérez、Francisco J. Moreno

  DOI：10.1021/jm011020u

  日期：2002.3.1

  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.