2-(4-hydroxybenzyl)-1,1-dioxo-λ⁶-isothiazolidine-3-carboxylic acid methyl ester | 409107-68-2

• 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: 2-(4-hydroxybenzyl)-1,1-dioxo-λ⁶-isothiazolidine-3-carboxylic acid methyl ester
• 英文别名: Methyl 2-[(4-hydroxyphenyl)methyl]-1,1-dioxo-1,2-thiazolidine-3-carboxylate
• CAS: 409107-68-2
• 化学式: C₁₂H₁₅NO₅S
• 分子量: 285.321
• InChiKey: LCDCGWBTJJPNNM-UHFFFAOYSA-N

物化性质

• 沸点：
  472.4±55.0 °C(Predicted)
• 密度：
  1.421±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  92.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-hydroxybenzyl)-1,1-dioxo-λ⁶-isothiazolidine-3-carboxylic acid methyl ester 在 palladium diacetate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 6.0h， 生成 2-(4'-methoxy-biphenyl-4-ylmethyl)-1,1-dioxo-λ⁶-isothiazolidine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Sultam Hydroxamates as Novel Matrix Metalloproteinase Inhibitors

  摘要：

  In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (NIMP-2 IC50 = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structure of 26 in MMP-13 confirms the key hydrogen bonds and prime side binding in the active site.

  DOI：

  10.1021/jm049833g
• 作为产物：
  描述：

  1,1-dioxoisothiazolidine-3-carboxylic acid methyl ester 在 palladium on activated charcoal 氢气 、 四丁基碘化铵 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(4-hydroxybenzyl)-1,1-dioxo-λ⁶-isothiazolidine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Conversion of potent MMP inhibitors into selective TACE inhibitors

  摘要：

  Novel sultam hydroxamates with potent MMP activity were transformed into potent TACE inhibitors, lacking MMP activity. To accomplish this we relied on structural differences between the MMP and TACE Sl' pockets and the known advantageous tit of a 2-methyl-4-quinolinylmethoxyphenyl group into this region. From this approach, compound 7d was identified as a potent TACE inhibitor (IC50 = 3.7 nM) that lacked MMP-1, -2, -9, and -13 activity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.078

文献信息

• Conversion of potent MMP inhibitors into selective TACE inhibitors
  作者：Robert J. Cherney、Bryan W. King、John L. Gilmore、Rui-Qin Liu、Maryanne B. Covington、James J.-W. Duan、Carl P. Decicco

  DOI：10.1016/j.bmcl.2005.10.078

  日期：2006.2

  Novel sultam hydroxamates with potent MMP activity were transformed into potent TACE inhibitors, lacking MMP activity. To accomplish this we relied on structural differences between the MMP and TACE Sl' pockets and the known advantageous tit of a 2-methyl-4-quinolinylmethoxyphenyl group into this region. From this approach, compound 7d was identified as a potent TACE inhibitor (IC50 = 3.7 nM) that lacked MMP-1, -2, -9, and -13 activity. (c) 2005 Elsevier Ltd. All rights reserved.
• Sultam Hydroxamates as Novel Matrix Metalloproteinase Inhibitors
  作者：Robert J. Cherney、Ruowei Mo、Dayton T. Meyer、Karl D. Hardman、Rui-Qin Liu、Maryanne B. Covington、Mingxin Qian、Zelda R. Wasserman、David D. Christ、James M. Trzaskos、Robert C. Newton、Carl P. Decicco

  DOI：10.1021/jm049833g

  日期：2004.6.1

  In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (NIMP-2 IC50 = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structure of 26 in MMP-13 confirms the key hydrogen bonds and prime side binding in the active site.