Arylsulfonylpiperazine, 15 | 1043476-09-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: Arylsulfonylpiperazine, 15
• 英文别名: 1-(4-nitrophenyl)sulfonyl-4-[3-(trifluoromethyl)pyridin-2-yl]piperazine
• CAS: 1043476-09-0
• 化学式: C₁₆H₁₅F₃N₄O₄S
• 分子量: 416.381
• InChiKey: CKTTYXLQVRUIJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Arylsulfonylpiperazine, 15 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Discovery and Structure–Activity Relationship of Potent and Selective Covalent Inhibitors of Transglutaminase 2 for Huntington’s Disease

  摘要：

  Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit 7d, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay.

  DOI：

  10.1021/jm201310y
• 作为产物：
  描述：

  1-[3-(三氟甲基)吡啶-2-基]哌嗪 、 对硝基苯磺酰氯 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 Arylsulfonylpiperazine, 15
  参考文献：
  名称：

  Discovery and Structure–Activity Relationship of Potent and Selective Covalent Inhibitors of Transglutaminase 2 for Huntington’s Disease

  摘要：

  Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit 7d, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay.

  DOI：

  10.1021/jm201310y

文献信息

• Discovery and Initial SAR of Arylsulfonylpiperazine Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)
  作者：Daqing Sun、Zhulun Wang、Yongmei Di、Juan C. Jaen、Marc Labelle、Ji Ma、Shichang Miao、Athena Sudom、Liang Tang、Craig S. Tomooka、Hua Tu、Stefania Ursu、Nigel Walker、Xuelei Yan、Qiuping Ye、Jay P. Powers

  DOI：10.1016/j.bmcl.2008.05.025

  日期：2008.6

  High-throughput screening of a small-molecule compound library resulted in the identification of a series of arylsulfonylpiperazines that are potent and selective inhibitors of human 11beta-Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD1). Optimization of the initial lead resulted in the discovery of compound (R)-45 (11beta-HSD1 IC(50)=3nM).
• Discovery and Structure–Activity Relationship of Potent and Selective Covalent Inhibitors of Transglutaminase 2 for Huntington’s Disease
  作者：Michael E. Prime、Ole A. Andersen、John J. Barker、Mark A. Brooks、Robert K. Y. Cheng、Ian Toogood-Johnson、Stephen M. Courtney、Frederick A. Brookfield、Christopher J. Yarnold、Richard W. Marston、Peter D. Johnson、Siw F. Johnsen、Jordan J. Palfrey、Darshan Vaidya、Sayeh Erfan、Osamu Ichihara、Brunella Felicetti、Shilpa Palan、Anna Pedret-Dunn、Sabine Schaertl、Ina Sternberger、Andreas Ebneth、Andreas Scheel、Dirk Winkler、Leticia Toledo-Sherman、Maria Beconi、Douglas Macdonald、Ignacio Muñoz-Sanjuan、Celia Dominguez、John Wityak

  DOI：10.1021/jm201310y

  日期：2012.2.9

  Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit 7d, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay.