(S)-3-methyl-2-[8-(2-oxo-oxazolidin-3-yl)-dibenzofuran-3-sulfonylamino]-butyric acid tert-butyl ester | 1025719-35-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (S)-3-methyl-2-[8-(2-oxo-oxazolidin-3-yl)-dibenzofuran-3-sulfonylamino]-butyric acid tert-butyl ester
• 英文别名: (S)-tert-butyl 3-methyl-2-(8-(2-oxooxazolidin-3-yl)dibenzo[b,d]furan-3-sulfonamido)butanoate；tert-butyl (2S)-3-methyl-2-[[8-(2-oxo-1,3-oxazolidin-3-yl)dibenzofuran-3-yl]sulfonylamino]butanoate
• CAS: 1025719-35-0
• 化学式: C₂₄H₂₈N₂O₇S
• 分子量: 488.562
• InChiKey: CGUMNGHIHVFBCS-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-3-methyl-2-[8-(2-oxo-oxazolidin-3-yl)-dibenzofuran-3-sulfonylamino]-butyric acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以79%的产率得到MMP145
  参考文献：
  名称：

  Identification of an Orally Efficacious Matrix Metalloprotease 12 Inhibitor for Potential Treatment of Asthma

  摘要：

  MMP-12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been observed in the lungs of asthmatic patients. Compound 27 was identified as a potent and selective MMP-12 inhibitor possessing good physicochemical properties. In pharmacological studies, the compound was orally efficacious in an MMP-12 induced ear-swelling inflammation model in the mouse with a good dose response. This compound also exhibited oral efficacy in a naturally Ascaris-sensitized sheep asthma model showing significant inhibition of the late phase response to allergen challenge. This compound has been considered for further development as a treatment therapy for asthma.

  DOI：

  10.1021/jm900809r
• 作为产物：
  描述：

  3-氨基二苯并呋喃 在 盐酸 、 二氧化硫 、 溴 、 氯 、 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium butanolate 、 三(邻甲基苯基)磷 、 copper dichloride 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 sodium nitrite 作用下， 以 二氯甲烷 、 水 、 溶剂黄146 、 甲苯 为溶剂， 反应 70.0h， 生成 (S)-3-methyl-2-[8-(2-oxo-oxazolidin-3-yl)-dibenzofuran-3-sulfonylamino]-butyric acid tert-butyl ester
  参考文献：
  名称：

  Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD)

  摘要：

  Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodeling of damaged alveoli in COPD and asthma. The goal of this project is to develop and identify an orally potent and selective small molecule inhibitor of MMP-12 for treatment of COPD and asthma. Syntheses and structure-activity relationship (SAR) studies of a series of dibenzofuran (DBF) sulfonamides as MMP-12 inhibitors are described. Potent inhibitors of MMP-12 with excellent selectivity against other MMPs were identified. Compound 26 (MMP118), which exhibits excellent oral efficacy in the MMP-12 induced ear-swelling inflammation and lung inflammation mouse models, had been successfully advanced into Development Track status. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.046

文献信息

• WO2008/57254
  申请人：——

  公开号：——

  公开（公告）日：——
• Identification of an Orally Efficacious Matrix Metalloprotease 12 Inhibitor for Potential Treatment of Asthma
  作者：Wei Li、Jianchang Li、Yuchuan Wu、Fabio Rancati、Stefania Vallese、Luca Raveglia、Junjun Wu、Rajeev Hotchandani、Nathan Fuller、Kristina Cunningham、Paul Morgan、Susan Fish、Rustem Krykbaev、Xin Xu、Steve Tam、Samuel J. Goldman、William Abraham、Cara Williams、Joseph Sypek、Tarek S. Mansour

  DOI：10.1021/jm900809r

  日期：2009.9.10

  MMP-12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been observed in the lungs of asthmatic patients. Compound 27 was identified as a potent and selective MMP-12 inhibitor possessing good physicochemical properties. In pharmacological studies, the compound was orally efficacious in an MMP-12 induced ear-swelling inflammation model in the mouse with a good dose response. This compound also exhibited oral efficacy in a naturally Ascaris-sensitized sheep asthma model showing significant inhibition of the late phase response to allergen challenge. This compound has been considered for further development as a treatment therapy for asthma.
• Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD)
  作者：Yuchuan Wu、Jianchang Li、Junjun Wu、Paul Morgan、Xin Xu、Fabio Rancati、Stefania Vallese、Luca Raveglia、Rajeev Hotchandani、Nathan Fuller、Joel Bard、Kristina Cunningham、Susan Fish、Rustem Krykbaev、Steve Tam、Samuel J. Goldman、Cara Williams、Tarek S. Mansour、Eddine Saiah、Joseph Sypek、Wei Li

  DOI：10.1016/j.bmcl.2011.11.046

  日期：2012.1

  Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodeling of damaged alveoli in COPD and asthma. The goal of this project is to develop and identify an orally potent and selective small molecule inhibitor of MMP-12 for treatment of COPD and asthma. Syntheses and structure-activity relationship (SAR) studies of a series of dibenzofuran (DBF) sulfonamides as MMP-12 inhibitors are described. Potent inhibitors of MMP-12 with excellent selectivity against other MMPs were identified. Compound 26 (MMP118), which exhibits excellent oral efficacy in the MMP-12 induced ear-swelling inflammation and lung inflammation mouse models, had been successfully advanced into Development Track status. (C) 2011 Elsevier Ltd. All rights reserved.