(3R,6R)-6-(hydroxymethyl)-4,4-dimethyl-3-[[(1R)-1-phenylethyl]amino]oxan-2-one | 329041-26-1

• 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: (3R,6R)-6-(hydroxymethyl)-4,4-dimethyl-3-[[(1R)-1-phenylethyl]amino]oxan-2-one
• CAS: 329041-26-1
• 化学式: C₁₆H₂₃NO₃
• 分子量: 277.364
• InChiKey: JZWGBKVPRSJZRN-BNOWGMLFSA-N

物化性质

• 沸点：
  439.6±35.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R,6R)-6-(hydroxymethyl)-4,4-dimethyl-3-[[(1R)-1-phenylethyl]amino]oxan-2-one 在 palladium on activated charcoal 吡啶 、 氢气 、 对甲苯磺酰氯 作用下， 以 甲醇 为溶剂， 生成 (1R,4R)-8,8-二甲基-2-氧杂-5-氮杂双环[2.2.2]辛烷-3-酮
  参考文献：
  名称：

  Discovery of 3,3-dimethyl-5-hydroxypipecolic hydroxamate-based inhibitors of aggrecanase and MMP-13

  摘要：

  A series of pipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was discovered based on screening known inhibitors of TNF-alpha converting enzyme (TACE). Potency versus aggrecanase was optimized by modification of the benzyloxyaryl-sulfonamide group. Incorporation of geminal alkyl substitution at the 3-position of the piperidine ring improved metabolic stability, presumably by increasing steric hindrance around the metabolically labile hydroxamic acid. This modification also resulted in dramatic improvement of aggrecanase activity with a slight reduction in selectivity versus MMP-1. Synthesis, structure activity relationships, and strategies to reduce metabolic clearance are described. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.105
• 作为产物：
  描述：

  (2R)-3,3-dimethyl-2-(1-(R)-phenyl-ethylamino)-hex-5-enenitrile 在 盐酸 、 potassium carbonate 、 氢喹啉 9-菲基醚 、 potassium hexacyanoferrate(III) 作用下， 以 水 、 叔丁醇 为溶剂， 生成 (3R,6R)-6-(hydroxymethyl)-4,4-dimethyl-3-[[(1R)-1-phenylethyl]amino]oxan-2-one
  参考文献：
  名称：

  Discovery of 3,3-dimethyl-5-hydroxypipecolic hydroxamate-based inhibitors of aggrecanase and MMP-13

  摘要：

  A series of pipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was discovered based on screening known inhibitors of TNF-alpha converting enzyme (TACE). Potency versus aggrecanase was optimized by modification of the benzyloxyaryl-sulfonamide group. Incorporation of geminal alkyl substitution at the 3-position of the piperidine ring improved metabolic stability, presumably by increasing steric hindrance around the metabolically labile hydroxamic acid. This modification also resulted in dramatic improvement of aggrecanase activity with a slight reduction in selectivity versus MMP-1. Synthesis, structure activity relationships, and strategies to reduce metabolic clearance are described. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.105

文献信息

• Discovery of 3,3-dimethyl-5-hydroxypipecolic hydroxamate-based inhibitors of aggrecanase and MMP-13
  作者：Mark C. Noe、Vijayalakshmi Natarajan、Sheri L. Snow、Peter G. Mitchell、Lori Lopresti-Morrow、Lisa M. Reeves、Sue A. Yocum、Thomas J. Carty、John A. Barberia、Francis J. Sweeney、Jennifer L. Liras、Marcie Vaughn、Joel R. Hardink、Joel M. Hawkins、Christopher Tokar

  DOI：10.1016/j.bmcl.2005.03.105

  日期：2005.6

  A series of pipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was discovered based on screening known inhibitors of TNF-alpha converting enzyme (TACE). Potency versus aggrecanase was optimized by modification of the benzyloxyaryl-sulfonamide group. Incorporation of geminal alkyl substitution at the 3-position of the piperidine ring improved metabolic stability, presumably by increasing steric hindrance around the metabolically labile hydroxamic acid. This modification also resulted in dramatic improvement of aggrecanase activity with a slight reduction in selectivity versus MMP-1. Synthesis, structure activity relationships, and strategies to reduce metabolic clearance are described. (c) 2005 Elsevier Ltd. All rights reserved.