N-benzyl-S-chloroisothiocarbamoyl chloride | 55000-02-7

• 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: N-benzyl-S-chloroisothiocarbamoyl chloride
• 英文别名: (N-benzyl-C-chlorocarbonimidoyl) thiohypochlorite
• CAS: 55000-02-7
• 化学式: C₈H₇Cl₂NS
• 分子量: 220.122
• InChiKey: WJLIFAYBQIJBFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  37.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-benzyl-S-chloroisothiocarbamoyl chloride 在 三乙胺 作用下， 以 乙醚 、 正己烷 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  N-Benzylpiperidine derivatives of 1,2,4-thiadiazolidinone as new acetylcholinesterase inhibitors

  摘要：

  A new family of 1,2,4-thiadiazolidinone derivatives containing the N-benzylpiperidine fragment has been synthesised. The acetylcholinesterase (AChE) inhibitory activity of all compounds was measured using Ellman's method and some of them turned out to be as potent as tacrine. Furthermore, compound 13 was as active as tacrine in reversing the blockade induced by tubocurarine at rat neuromuscular junction. Additionally, receptor binding studies provided new lead compounds for further development of alpha (2)-adrenergic and sigma-receptor antagonists. Molecular dynamic simulation using X-ray crystal structure of AChE from Torpedo californica was used to explain the possible binding mode of these new compounds. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)01166-1
• 作为产物：
  描述：

  异硫氰酸苯甲酯 在 氯 作用下， 以 正己烷 为溶剂， 生成 N-benzyl-S-chloroisothiocarbamoyl chloride
  参考文献：
  名称：

  Enzyme inhibitors

  摘要：

  通式（I）的化合物： 其中A、E、G、X、Y和键- - - 取不同含义，在制备药物配方中有用，例如在治疗涉及GSK-3的疾病中，包括阿尔茨海默病或非依赖胰岛素糖尿病，或高增殖性疾病，如癌症、组织发育不良或异型增生、银屑病、动脉硬化或再狭窄症。

  公开号：

  US20030195238A1

文献信息

• 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.
• Identification of small molecules that inhibit GSK-3β through virtual screening
  作者：Nam Sook Kang、Gil Nam Lee、Chi Hyun Kim、Myung Ae Bae、Ikyon Kim、Young Sik Cho

  DOI：10.1016/j.bmcl.2008.10.120

  日期：2009.1

  Glycogen synthase kinase-3 beta (GSK-3 beta) is involved in glycogen metabolism, neuronal cell development, osteoblast differentiation. Small molecule inhibitors of GSK-3 beta have various therapeutic potential for the treatment of diabetes type II, bipolar disorders, stroke and chronic in. ammatory disease.To identify GSK-3 beta inhibitors with novel scaffold from chemical library, we primarily screened out putative inhibitors through computer modeling and subsequently evaluated the inhibitory activity of selected compounds against GSK-3 beta by in vitro Z'-LYTE (TM) assay. A series of compound KRMs strongly inhibited phosphorylation of its substrate with IC50 value of approximately 0.5 mu M. Also, we demonstrated that KRM-189 and KRM-191 competed with ATP for GSK-3 beta, leading to decreased V-max and constant Km with increasing concentrations of ATP as determined from Lineweaver-Berk equation. Moreover, they showed the selectivity for GSK-3 beta over other kinases with IC50 values of 2 to 10 mu M or more Incubation of cells with KRM-191 with highly selective and potent inhibitory activity caused accumulation of beta-catenin, downstream of GSK-3 beta signaling pathway, indicating that small molecule can prevent degradation of beta-catenin via GSK-3 beta inhibition. Our results suggest that modeling in combination with in vitro assays can be used for the identification of selective and potent inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.