(1S,3S,5R,9S)-9-(4-Hydroxymethyl-3,3-dimethyl-2-oxo-pyrrolidin-1-yl)-bicyclo[3.3.1]nonane-3-carboxylic acid methyl ester | 910789-96-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (1S,3S,5R,9S)-9-(4-Hydroxymethyl-3,3-dimethyl-2-oxo-pyrrolidin-1-yl)-bicyclo[3.3.1]nonane-3-carboxylic acid methyl ester
• CAS: 910789-96-7
• 化学式: C₁₈H₂₉NO₄
• 分子量: 323.433
• InChiKey: BARXJTBJGLIUEU-SISPYFCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.83
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  66.84
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (1S,3S,5R,9S)-9-(4-Hydroxymethyl-3,3-dimethyl-2-oxo-pyrrolidin-1-yl)-bicyclo[3.3.1]nonane-3-carboxylic acid methyl ester 在 N,N-二甲基丙烯基脲 、 lithium hydroxide 、 sodium hydride 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 10.0h， 生成
  参考文献：
  名称：

  A Highly Efficient Synthesis of Potent and Selective Butyrolactam Inhibitors of 11β-Hsd1

  摘要：

  A convergent synthesis of structurally novel butyrolactam 11 beta-HSD1 inhibitors is described. The approach features an efficient Ireland-Claisen reaction to construct a highly substituted aldehyde building block which is converted to a lactam via a tandem reductive amination/cyclization sequence. The generality of the synthetic sequence is demonstrated during the preparation of two additional potent 11 beta-HSD1 inhibitors.

  DOI：

  10.1021/ol061429j
• 作为产物：
  描述：

  9-oxo-bicyclo[3.3.1]nonane-3-carboxylic acid methyl ester 在 Amberlyst 15 、 4 A molecular sieve 、 四丁基氟化铵 、 氢气 、 sodium methylate 、 三乙酰氧基硼氢化钠 、 镍 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 、 甲苯 为溶剂， 20.0~90.0 ℃ 、101.33 kPa 条件下， 反应 30.0h， 生成 (1S,3S,5R,9S)-9-(4-Hydroxymethyl-3,3-dimethyl-2-oxo-pyrrolidin-1-yl)-bicyclo[3.3.1]nonane-3-carboxylic acid methyl ester
  参考文献：
  名称：

  A Highly Efficient Synthesis of Potent and Selective Butyrolactam Inhibitors of 11β-Hsd1

  摘要：

  A convergent synthesis of structurally novel butyrolactam 11 beta-HSD1 inhibitors is described. The approach features an efficient Ireland-Claisen reaction to construct a highly substituted aldehyde building block which is converted to a lactam via a tandem reductive amination/cyclization sequence. The generality of the synthetic sequence is demonstrated during the preparation of two additional potent 11 beta-HSD1 inhibitors.

  DOI：

  10.1021/ol061429j

文献信息

• Discovery of orally active butyrolactam 11β-HSD1 inhibitors
  作者：Vince S.C. Yeh、Ravi Kurukulasuriya、Steven Fung、Katina Monzon、William Chiou、Jiahong Wang、Deanne Stolarik、Hovis Imade、Robin Shapiro、Victoria Knourek-Segel、Eugene Bush、Denise Wilcox、Phong T. Nguyen、Michael Brune、Peer Jacobson、J.T. Link

  DOI：10.1016/j.bmcl.2006.08.034

  日期：2006.11

  A series of metabolically stable butyrolactam 11 beta-HSD1 inhibitors have been synthesized and biologically evaluated. These compounds exhibit excellent HSD1 potency and HSD2 selectivity, pharmacokinetic, and pharmacodynamic profiles. (c) 2006 Elsevier Ltd. All rights reserved.