(2S,3R)-3-[[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]methyl]-4-oxoazetidine-2-carboxylic acid | 705962-15-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (2S,3R)-3-[[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]methyl]-4-oxoazetidine-2-carboxylic acid
• CAS: 705962-15-8
• 化学式: C₁₅H₂₄N₂O₅
• 分子量: 312.366
• InChiKey: GLYQNFBJRZKPHV-MNOVXSKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3R)-3-[[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]methyl]-4-oxoazetidine-2-carboxylic acid 在 N-甲基咪唑 、 苯甲基-2-磺酰三硝基三氮唑 、 Wang resin 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 40.08h， 生成 2-cyclopropyl-4-hydroxy-6-methoxy-4-phenyl-3-(1,3-thiazol-2-)-3,4-dihydroisoquinolin-1(2H)-one
  参考文献：
  名称：

  Beta lactam compounds and their use as inhibitors of tryptase

  摘要：

  提供了具有以下结构的β-内酰胺化合物 1 其中B、A、D、R 1 、R 2 、R 3 和X 1 如本文所定义，并且这些化合物可用作组胺酶、凝血酶、胰蛋白酶、Xa因子、VIIa因子和尿激酶型纤溶酶原激活剂的抑制剂，并可用于预防和/或治疗哮喘和过敏性鼻炎。

  公开号：

  US20040147502A1
• 作为产物：
  描述：

  N-Boc-4-哌啶甲醇 在 咪唑 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2S,3R)-3-[[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]methyl]-4-oxoazetidine-2-carboxylic acid
  参考文献：
  名称：

  Solid-phase synthesis and SAR of 4-carboxy-2-azetidinone mechanism-based tryptase inhibitors

  摘要：

  A series of nonguanidine N1-activated C4-carboxy azetidinone tryptase inhibitors was prepared by solid-phase methodology to quickly assess the SAR associated with distal functionality on the N1-activating group. From these studies, potent inhibitors with improved specificity were discovered.

  DOI：

  10.1016/j.bmcl.2004.02.012

文献信息

• Synthesis of potent and highly selective nonguanidine azetidinone inhibitors of human tryptase
  作者：Gregory S Bisacchi、William A Slusarchyk、Scott A Bolton、Karen S Hartl、Glenn Jacobs、Arvind Mathur、Wei Meng、Martin L Ogletree、Zulan Pi、James C Sutton、Uwe Treuner、Robert Zahler、Guohua Zhao、Steven M Seiler

  DOI：10.1016/j.bmcl.2004.02.011

  日期：2004.5

  Azetidinones such as BMS-363131 (2) and BMS-363130 (3), which contain a guanidine group in the C-3 side chain were previously shown to be very potent inhibitors of human tryptase with high selectivity versus other serine proteases, including trypsin. In this letter, we describe the discovery of a number of potent azetidinone tryptase inhibitors in which the guanidine moiety at the ring C-3 position is replaced with primary or secondary amine or aminopyridine functionality. In particular, BMS-354326 (4) is a highly potent tryptase inhibitor (IC50 1.8 nM), which has excellent selectivity against trypsin and most other related serine proteases. (C) 2004 Elsevier Ltd. All rights reserved.