(2S)-3-methyl-2-[[8-[5-(2-methylpropyl)-1,2,4-oxadiazol-3-yl]dibenzofuran-3-yl]sulfonylamino]butanoic acid | 1354827-64-7

• 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: (2S)-3-methyl-2-[[8-[5-(2-methylpropyl)-1,2,4-oxadiazol-3-yl]dibenzofuran-3-yl]sulfonylamino]butanoic acid
• CAS: 1354827-64-7
• 化学式: C₂₃H₂₅N₃O₆S
• 分子量: 471.534
• InChiKey: SXULEDPOWFISCW-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-氨基二苯并呋喃 在 盐酸 、 四(三苯基膦)钯 、 二氧化硫 、 水 、 羟胺 、 溴 、 氯 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 N,N-二异丙基乙胺 、 copper dichloride 、 lithium hydroxide 、 sodium nitrite 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 反应 86.0h， 生成 (2S)-3-methyl-2-[[8-[5-(2-methylpropyl)-1,2,4-oxadiazol-3-yl]dibenzofuran-3-yl]sulfonylamino]butanoic acid
  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

• 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.