3-[2,3-dihydro-1,4-benzodioxin-6-ylmethylamino]-4-fluorobenzonitrile | 1262338-85-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 3-[2,3-dihydro-1,4-benzodioxin-6-ylmethylamino]-4-fluorobenzonitrile
• 英文别名: 3-[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]-4-fluorobenzonitrile；3-[(2,3-Dihydro-1,4-benzodioxin-6-ylmethyl)amino]-4-fluorobenzonitrile；3-(2,3-dihydro-1,4-benzodioxin-6-ylmethylamino)-4-fluorobenzonitrile
• CAS: 1262338-85-1
• 化学式: C₁₆H₁₃FN₂O₂
• 分子量: 284.29
• InChiKey: PKOCJLVNPGNDEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  54.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[2,3-dihydro-1,4-benzodioxin-6-ylmethylamino]-4-fluorobenzonitrile 在 二正丁基氧化锡 N-甲基吗啉 、 叠氮基三甲基硅烷 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 10.0h， 生成 N-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-N-[2-fluoro-5-(1H-tetrazol-5-yl)phenyl]-3-methylbutanamide
  参考文献：
  名称：

  [EN] TETRAZOLE DERIVATIVES
  [FR] DÉRIVÉS DE TÉTRAZOLE

  摘要：

  公开号：

  WO2011006935A3
• 作为产物：
  描述：

  1,4-苯并二恶烷-6-甲醛 在 sodium tetrahydroborate 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 24.0h， 生成 3-[2,3-dihydro-1,4-benzodioxin-6-ylmethylamino]-4-fluorobenzonitrile
  参考文献：
  名称：

  Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of Carboxylic Acids

  摘要：

  Antagonism of the CRTH2 receptor represents a very attractive target for a variety of allergic diseases. Most CRTH2 antagonists known to date possess a carboxylic acid moiety, which is essential for binding. However, potential acid metabolites O-acyl glucuronides might be linked to idiosynchratic toxicity in humans. In this communication, we describe a new series of compounds that lack the carboxylic acid moiety. Compounds with high affinity (K(i) < 10 nM) for the receptor have been identified. Subsequent optimization succeeded in reducing the high metabolic clearance of the first compounds in human and rat liver microsomes. At the same time, inhibition of the CYP isoforms was optimized, giving rise to stable compounds with an acceptable CYP inhibition profile (IC(50) CYP2C9 and 2C19 > 1 mu M). Taken together, these data show that compounds devoid of carboxylic acid groups could represent an interesting alternative to current CRTH2 antagonists in development.

  DOI：

  10.1021/ml200223s

文献信息

• TETRAZOLE DERIVATIVES
  申请人：Crosignani Stefano

  公开号：US20120115869A1

  公开（公告）日：2012-05-10

  The present invention relates to compounds of formula (I) for use as pharmaceutical active compounds, as well as pharmaceutical formulations containing the same, for the treatment of allergic diseases.

  本发明涉及式（I）的化合物，用作药物活性化合物，以及包含相同化合物的制药配方，用于治疗过敏性疾病。
• Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of Carboxylic Acids
  作者：Stefano Crosignani、Catherine Jorand-Lebrun、Gordon Campbell、Adeline Prêtre、Tania Grippi-Vallotton、Anna Quattropani、Gwenaelle Bouscary-Desforges、Agnes Bombrun、Marc Missotten、Yves Humbert、Christèle Frémaux、Mikaël Pâquet、Kamel El Harkani、Charles G. Bradshaw、Christophe Cleva、Nada Abla、Hamina Daff、Olivier Schott、Pierre-André Pittet、Jean-François Arrighi、Marilène Gaudet、Zoë Johnson

  DOI：10.1021/ml200223s

  日期：2011.12.8

  Antagonism of the CRTH2 receptor represents a very attractive target for a variety of allergic diseases. Most CRTH2 antagonists known to date possess a carboxylic acid moiety, which is essential for binding. However, potential acid metabolites O-acyl glucuronides might be linked to idiosynchratic toxicity in humans. In this communication, we describe a new series of compounds that lack the carboxylic acid moiety. Compounds with high affinity (K(i) < 10 nM) for the receptor have been identified. Subsequent optimization succeeded in reducing the high metabolic clearance of the first compounds in human and rat liver microsomes. At the same time, inhibition of the CYP isoforms was optimized, giving rise to stable compounds with an acceptable CYP inhibition profile (IC(50) CYP2C9 and 2C19 > 1 mu M). Taken together, these data show that compounds devoid of carboxylic acid groups could represent an interesting alternative to current CRTH2 antagonists in development.
• [EN] TETRAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS DE TÉTRAZOLE
  申请人：MERCK SERONO SA

  公开号：WO2011006935A3

  公开（公告）日：2013-03-28