3-[(2S,3R)-1-(tert-Butyl-dimethyl-silanyl)-2-carboxy-4-oxo-azetidin-3-ylmethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester | 479622-21-4

• 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)-1-(tert-Butyl-dimethyl-silanyl)-2-carboxy-4-oxo-azetidin-3-ylmethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester
• CAS: 479622-21-4
• 化学式: C₂₀H₃₆N₂O₅Si
• 分子量: 412.602
• InChiKey: CSRUSSIGJQWCIF-DMJDIKPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.55
• 重原子数：
  28.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  87.15
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-[(2S,3R)-1-(tert-Butyl-dimethyl-silanyl)-2-carboxy-4-oxo-azetidin-3-ylmethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester 在 TEA 、 四丁基氟化铵 、 碳酸氢钠 、 三氟乙酸 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 (2S,3R)-3-(1-{Benzyloxycarbonylamino-[(E)-benzyloxycarbonylimino]-methyl}-pyrrolidin-3-ylmethyl)-4-oxo-azetidine-2-carboxylic acid benzyl 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
• 作为产物：
  描述：

  1-苄基-3-羟甲基吡咯烷 在 palladium on activated charcoal 咪唑 、 氢气 、 碘 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 3-[(2S,3R)-1-(tert-Butyl-dimethyl-silanyl)-2-carboxy-4-oxo-azetidin-3-ylmethyl]-pyrrolidine-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：——

  公开号：US20040147502A1

  公开（公告）日：2004-07-29

  Beta lactam compounds are provided which have the structure 1 wherein B, A, D, R 1 , R 2 , R 3 and X 1 are as defined herein, and which are useful as inhibitors of tryptase, thrombin, trypsin, Factor Xa, Factor VIIa, and urokinase-type plasminogen activator and may be employed in preventing and/or treating asthma and allergic rhinitis.

  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。
• 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.