N-(4-((4-(2-(3,5-dimethylisoxazol-4-yl)ethyl)piperidin-1-ylsulfonyl)methyl)tetrahydro-2H-pyran-4-yl)-N-hydroxyformamide | 1313221-53-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-(4-((4-(2-(3,5-dimethylisoxazol-4-yl)ethyl)piperidin-1-ylsulfonyl)methyl)tetrahydro-2H-pyran-4-yl)-N-hydroxyformamide
• 英文别名: N-[4-[[4-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]piperidin-1-yl]sulfonylmethyl]oxan-4-yl]-N-hydroxyformamide
• CAS: 1313221-53-2
• 化学式: C₁₉H₃₁N₃O₆S
• 分子量: 429.538
• InChiKey: ISHINUUQDKDNHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 三甲基氯硅烷 、 palladium on carbon 、 氢气 、 羟胺 、 乙酸酐 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 丙醇 为溶剂， 生成 N-(4-((4-(2-(3,5-dimethylisoxazol-4-yl)ethyl)piperidin-1-ylsulfonyl)methyl)tetrahydro-2H-pyran-4-yl)-N-hydroxyformamide
  参考文献：
  名称：

  Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis

  摘要：

  A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure-activity and structure-property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This led to the identification of a pre-clinical candidate with excellent bioavailability across three species and predicting once daily dosing kinetics. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.028

文献信息

• Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis
  作者：Chris De Savi、Andrew Pape、Yvonne Sawyer、David Milne、Chris Davies、John G. Cumming、Attilla Ting、Scott Lamont、Peter D. Smith、Jonathon Tart、Ken Page、Peter Moore

  DOI：10.1016/j.bmcl.2011.04.028

  日期：2011.6

  A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure-activity and structure-property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This led to the identification of a pre-clinical candidate with excellent bioavailability across three species and predicting once daily dosing kinetics. (C) 2011 Elsevier Ltd. All rights reserved.