3-((2S,3R)-2-Benzyloxycarbonyl-4-oxo-azetidin-3-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester | 253177-06-9

• 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: 3-((2S,3R)-2-Benzyloxycarbonyl-4-oxo-azetidin-3-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester
• CAS: 253177-06-9
• 化学式: C₂₂H₃₀N₂O₅
• 分子量: 402.491
• InChiKey: MMWQBEYYWBMEGK-RWZMTBSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.88
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  84.94
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-((2S,3R)-2-Benzyloxycarbonyl-4-oxo-azetidin-3-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester 在 palladium on activated charcoal 盐酸 、 4-二甲氨基吡啶 、 TEA 、 氢气 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S,3R)-3-(1-Carbamimidoyl-piperidin-3-ylmethyl)-4-oxo-1-[4-(4-phenyl-butylcarbamoyl)-piperazine-1-carbonyl]-azetidine-2-carboxylic acid
  参考文献：
  名称：

  Synthesis of potent and highly selective inhibitors of human tryptase

  摘要：

  The serine protease tryptase has been implicated in allergic and inflammatory diseases and associated with asthma. The synthesis and SAR of a series of N1-activated-4-carboxy azetidinones are described, resulting in identification of BMS-363131 (2) as a potent inhibitor of human tryptase (IC50 < 1.7 nM) with high selectivity (>3000-fold) for tryptase versus related serine proteases including trypsin. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00689-3
• 作为产物：
  描述：

  3-哌啶甲酸乙酯 在 咪唑 、 lithium aluminium tetrahydride 、 四丁基氟化铵 、 碘 、 碳酸氢钠 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-((2S,3R)-2-Benzyloxycarbonyl-4-oxo-azetidin-3-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis of potent and highly selective inhibitors of human tryptase

  摘要：

  The serine protease tryptase has been implicated in allergic and inflammatory diseases and associated with asthma. The synthesis and SAR of a series of N1-activated-4-carboxy azetidinones are described, resulting in identification of BMS-363131 (2) as a potent inhibitor of human tryptase (IC50 < 1.7 nM) with high selectivity (>3000-fold) for tryptase versus related serine proteases including trypsin. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00689-3

文献信息

• Beta lactam compounds and their use as inhibitors of tryptase
  申请人：Bristol-Myers Squibb Co.

  公开号：US06335324B1

  公开（公告）日：2002-01-01

  Compounds of the formulas: are disclosed. These compounds inhibit tryptase as well as other enzyme systems or are selective tryptase inhibitors and are useful as antiinflammatory agents particularly in the treatment of chronic asthma.

  这些化合物的结构式已被披露。这些化合物抑制色胺酸蛋白酶以及其他酶系统，或者是选择性色胺酸蛋白酶抑制剂，并且在特别是治疗慢性哮喘方面作为抗炎药物是有用的。
• 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.