(S)-4-isobutyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide | 174466-65-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-4-isobutyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide
• 英文别名: (4S)-4-(2-methylpropyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one
• CAS: 174466-65-0
• 化学式: C₆H₁₂N₂O₃S
• 分子量: 192.239
• InChiKey: JAGLNMZWYYNRJI-YFKPBYRVSA-N

物化性质

• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-4-isobutyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide 在 sodium hydride 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 20.0h， 生成 (S)-4-Isobutyl-5-methyl-1,1-dioxo-2-phenylsulfanylmethyl-1λ6-[1,2,5]thiadiazolidin-3-one
  参考文献：
  名称：

  Potent and Specific Inhibition of Human Leukocyte Elastase, Cathepsin G and Proteinase 3 by Sulfone Derivatives Employing the 1,2,5-Thiadiazolidin-3-one 1,1 Dioxide Scaffold

  摘要：

  This paper describes the results of structure-activity relationship studies in a series of heterocyclic mechanism-based inhibitors based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold I and capable of interacting with the S-n and S-n' subsites of a serine proteinase. Sulfone derivatives of I were found to be highly effective, time-dependent inhibitors of human leukocyte elastase (HLE), cathepsin G (Cat G) and proteinase 3 (PR 3). The judicious selection of an R-1 group (accommodated at the primary specificity site S-1) that is based on the known substrate specificity of a target serine proteinase, was found to yield highly selective inhibitors. The presence of a benzyl group (R-2 = benzyl) at the S-2 subsite was found to lead to a pronounced enhancement in inhibitory potency. Furthermore, the effective use of computer graphics and modeling has led to the design of potent, water-soluble inhibitors. The results of these studies demonstrate that the 1,2,5-thiadiazolidin-3-one 1,1, dioxide platform provides an effective means for appending recognition elements in a well-defined vector relationship, and in fashioning highly-selective and potent inhibitors of serine proteinases. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00006-6
• 作为产物：
  描述：

  <(S)(-)> methyl -leucinate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以80%的产率得到(S)-4-isobutyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide
  参考文献：
  名称：

  含有手性磺胺乙内酰脲作为糖苷配基的假核苷的合成（II）

  摘要：

  从N-氨磺酰基氨基酸甲基酯开始，通过碱环化合成了一系列手性磺基缩乙胆苷。这些伪嘧啶杂环的区域选择性糖基化是在N-磺酰基氨基甲酸酯位置上的苄基保护基进行的。最佳的糖基化结果是通过对磺胺丁丹酮进行初步的甲硅烷基化，以及它们与四酰基核呋喃糖的缩合反应而获得的，从而产生呈β-异头构型的假核苷。

  DOI：

  10.1016/0040-4020(95)00932-9

文献信息

• Utilization of the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold in the design of potent inhibitors of serine proteases: SAR studies using carboxylates
  作者：Rongze Kuang、Jeffrey B. Epp、Sumei Ruan、Lee S. Chong、Radhika Venkataraman、Juan Tu、Shu He、Tien M. Truong、William C. Groutas

  DOI：10.1016/s0968-0896(00)00038-9

  日期：2000.5

  A series of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide and isothiazolidin-3-one 1,1 dioxide scaffolds has been synthesized and the inhibitory profile of these compounds toward human leukocyte elastase (HLE), cathepsin G (Cat G) and proteinase 3 (PR 3) was then determined. Most of the compounds were found to be potent, time-dependent inhibitors of elastase, with some

  合成了一系列基于1,2,5-噻二唑烷酮-3-1,1二氧化和异噻唑烷-3-3-1的二羧酸骨架的羧酸衍生物，这些化合物对人白细胞弹性蛋白酶（HLE）的抑制作用），然后测定组织蛋白酶G（Cat G）和蛋白酶3（PR 3）。发现大多数化合物是弹性蛋白酶的有效时间依赖性抑制剂，其中某些化合物的k（inact）/ K1值高达4,928,300 M（-1）s（-1）。发现基于1,2,5-噻二唑啉-3--1,1二氧化平台的羧酸衍生物的抑制能力受pKa和离去基团固有结构的影响。发现正确选择主要特异性组（R（I））可以导致对HLE的选择性抑制高于Cat G，但是，那些抑制HLE的化合物也抑制PR 3，尽管效率较低。这些化合物的可预测结合方式表明，在紧密相关的丝氨酸蛋白酶中，可以通过利用它们的S'亚位点的细微差别来形成特定丝氨酸蛋白酶的高选择性抑制剂。这项研究还表明，在存在抑制剂17的情况下，弹性蛋白酶对弹性蛋白的降解作用可以消除。
• Effects of structure on inhibitory activity in a series of mechanism-based inhibitors of human neutrophil elastase
  作者：Dengfeng Dou、Guijia He、Rongze Kuang、Qingfong Fu、Radhika Venkataraman、William C. Groutas

  DOI：10.1016/j.bmc.2010.07.071

  日期：2010.9

  A structurally-diverse series of carboxylate derivatives based on the 1,2,5-thiadiazolidin-one 1,1 dioxide scaffold were synthesized and used to probe the S' subsites of human neutrophil elastase (HNE) and neutrophil proteinase 3 (Pr 3). Several compounds are potent inhibitors of HNE but devoid of inhibitory activity toward Pr 3, suggesting that the S' subsites of HNE exhibit significant plasticity and can, unlike Pr 3, tolerate various large hydrophobic groups. The results provide a promising framework for the design of highly selective inhibitors of the two enzymes. (c) 2010 Elsevier Ltd. All rights reserved.
• 1,2,5-THIADIAZOLIDIN-3-ONE 1,1-DIOXIDE DERIVATIVES
  申请人：THE WICHITA STATE UNIVERSITY

  公开号：EP1011668A1

  公开（公告）日：2000-06-28
• EP1011668A4
  申请人：——

  公开号：EP1011668A4

  公开（公告）日：2001-08-16
• US6420401B1
  申请人：——

  公开号：US6420401B1

  公开（公告）日：2002-07-16