BMS-262084 | 253174-92-4

• 物质功能分类: 医药中间体 - 原料药中间体
• 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: BMS-262084
• 英文别名: 2-Azetidinecarboxylic acid, 3-(3-((aminoiminomethyl)amino)propyl)-1-((4-(((1,1-dimethylethyl)amino)carbonyl)-1-piperazinyl)carbonyl)-4-oxo-, (2S,3R)-；(2S,3R)-1-[4-(tert-butylcarbamoyl)piperazine-1-carbonyl]-3-[3-(diaminomethylideneamino)propyl]-4-oxoazetidine-2-carboxylic acid
• CAS: 253174-92-4
• 化学式: C₁₈H₃₁N₇O₅
• 分子量: 425.488
• InChiKey: MFTQITSPGQORDA-NEPJUHHUSA-N

物化性质

• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  175
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (2S,3R)-3-[3-[bis(phenylmethoxycarbonylamino)methylideneamino]propyl]-4-oxoazetidine-2-carboxylic acid 在 palladium on activated charcoal 盐酸 、 4-二甲氨基吡啶 、 氢气 、 四丁基碘化铵 、 碳酸氢钠 、 三乙胺 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 BMS-262084
  参考文献：
  名称：

  Synthesis and SAR of 4-carboxy-2-azetidinone mechanism-based tryptase inhibitors

  摘要：

  A series of N1-activated C4-carboxy azetidinones was prepared and tested as inhibitors of human tryptase. The key stereochemical and functional features required for potency, serine protease specificity and aqueous stability were determined. From these studies compound 2, BMS-262084, was identified as a potent and selective tryptase inhibitor which, when dosed intratracheally in ovalbumin-sensitized guinea pigs, reduced allergen-induced bronchoconstriction and inflammatory cell infiltration into the lung. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00688-1

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。
• [EN] AMIDINO AND GUANIDINO AZETIDINONE TRYPTASE INHIBITORS<br/>[FR] INHIBITEURS D'AMIDINO ET GUANIDINO AZETIDONONE TRYPTASE
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：WO1999067215A1

  公开（公告）日：1999-12-29

  (EN) Compounds of formulae (I), (II), (III).(FR) L'invention concerne des composés correspondant aux formules (I), (II) et (III).

  这是中文翻译： (EN) Compounds of formulae (I), (II), (III). 对应于公式(I)，(II)，(III)的化合物。 (FR) L'invention concerne des composés correspondant aux formules (I), (II) et (III). 该发明涉及对应于公式(I)，(II)，(III)的化合物。
• A Stereoselective Synthesis of BMS-262084, an Azetidinone-Based Tryptase Inhibitor
  作者：Xinhua Qian、Bin Zheng、Brian Burke、Manohar T. Saindane、David R. Kronenthal

  DOI：10.1021/jo010757o

  日期：2002.5.1

  A highly stereoselective synthesis of the novel tryptase inhibitor BMS-262084 was developed. Key to this synthesis was the discovery and development of a highly diastereoselective demethoxycarbonylation of diester 12 to form the trans-azetidinone 13. BMS-262084 was prepared in 10 steps from D-ornithine in 30% overall yield.
• Synthesis and SAR of 4-carboxy-2-azetidinone mechanism-based tryptase inhibitors
  作者：James C Sutton、Scott A Bolton、Karen S Hartl、Ming-Hsing Huang、Glenn Jacobs、Wei Meng、Martin L Ogletree、Zulan Pi、William A Schumacher、Steven M Seiler、William A Slusarchyk、Uwe Treuner、Robert Zahler、Guohua Zhao、Gregory S Bisacchi

  DOI：10.1016/s0960-894x(02)00688-1

  日期：2002.11

  A series of N1-activated C4-carboxy azetidinones was prepared and tested as inhibitors of human tryptase. The key stereochemical and functional features required for potency, serine protease specificity and aqueous stability were determined. From these studies compound 2, BMS-262084, was identified as a potent and selective tryptase inhibitor which, when dosed intratracheally in ovalbumin-sensitized guinea pigs, reduced allergen-induced bronchoconstriction and inflammatory cell infiltration into the lung. (C) 2002 Elsevier Science Ltd. All rights reserved.