(S)-4-Isobutyl-5-methyl-1,1-dioxo-2-phenylsulfanylmethyl-1λ6-[1,2,5]thiadiazolidin-3-one | 170919-10-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (S)-4-Isobutyl-5-methyl-1,1-dioxo-2-phenylsulfanylmethyl-1λ6-[1,2,5]thiadiazolidin-3-one
• CAS: 170919-10-5
• 化学式: C₁₄H₂₀N₂O₃S₂
• 分子量: 328.456
• InChiKey: HZTCJUUORAXPHC-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.17
• 重原子数：
  21.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  57.69
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-4-Isobutyl-5-methyl-1,1-dioxo-2-phenylsulfanylmethyl-1λ6-[1,2,5]thiadiazolidin-3-one 在 磺酰氯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 生成 (S)-4-Isobutyl-5-methyl-1,1-dioxo-2-(3-trifluoromethyl-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)-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

文献信息

• 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.