methyl 3-fluoro-5-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6-carboxylate | 1027332-94-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 3-fluoro-5-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6-carboxylate
• 英文别名: Methyl 3-fluoro-5-oxo-6,7,8,9-tetrahydrobenzo[7]annulene-6-carboxylate
• CAS: 1027332-94-0
• 化学式: C₁₃H₁₃FO₃
• 分子量: 236.243
• InChiKey: XQARQYZJVVAOSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-fluoro-5-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6-carboxylate 、 硝酸胍 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以2.3 g的产率得到10-fluoro-2-amino-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-ol
  参考文献：
  名称：

  Rotationally Constrained 2,4-Diamino-5,6-disubstituted Pyrimidines: A New Class of Histamine H₄ Receptor Antagonists with Improved Druglikeness and in Vivo Efficacy in Pain and Inflammation Models

  摘要：

  A new structural class of histamine H-4 receptor antagonists (6-14) was designed based on rotationally restricted 2,4-diaminopyrimidines. Series compounds showed potent and selective in vitro H-4 antagonism across multiple species, good CNS penetration, improved PK properties compared to reference H-4 antagonists, functional H-4 antagonism in cellular and in vivo pharmacological assays, and in vivo anti-inflammatory and antinociceptive efficacy. One compound, 10 (A-943931), combined the best features of the series in a single molecule and is an excellent tool compound to probe H-4 pharmacology. It is a potent H-4 antagonist in functional assays across species (FLIPR Ca2+ flux, K-b < 5.7 nM), has high (> 190x) selectivity for H-4, and combines good PK in rats and mice (t(1/2) of 2.6 and 1.6 h, oral bioavailability of 37% and 90%) with anti-inflammatory activity (ED50 = 37 mu mol/kg, mouse) and efficacy in pain models (thermal hyperalgesia, ED50 = 72 mu mol/kg, rat).

  DOI：

  10.1021/jm800670r
• 作为产物：
  描述：

  8-氟-1-苯并环庚酮 、 碳酸二甲酯 在 sodium hydride 作用下， 以 mineral oil 为溶剂， 反应 3.0h， 以6.2 g的产率得到methyl 3-fluoro-5-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6-carboxylate
  参考文献：
  名称：

  Rotationally Constrained 2,4-Diamino-5,6-disubstituted Pyrimidines: A New Class of Histamine H₄ Receptor Antagonists with Improved Druglikeness and in Vivo Efficacy in Pain and Inflammation Models

  摘要：

  A new structural class of histamine H-4 receptor antagonists (6-14) was designed based on rotationally restricted 2,4-diaminopyrimidines. Series compounds showed potent and selective in vitro H-4 antagonism across multiple species, good CNS penetration, improved PK properties compared to reference H-4 antagonists, functional H-4 antagonism in cellular and in vivo pharmacological assays, and in vivo anti-inflammatory and antinociceptive efficacy. One compound, 10 (A-943931), combined the best features of the series in a single molecule and is an excellent tool compound to probe H-4 pharmacology. It is a potent H-4 antagonist in functional assays across species (FLIPR Ca2+ flux, K-b < 5.7 nM), has high (> 190x) selectivity for H-4, and combines good PK in rats and mice (t(1/2) of 2.6 and 1.6 h, oral bioavailability of 37% and 90%) with anti-inflammatory activity (ED50 = 37 mu mol/kg, mouse) and efficacy in pain models (thermal hyperalgesia, ED50 = 72 mu mol/kg, rat).

  DOI：

  10.1021/jm800670r

文献信息

• Macrocyclic Benzofused Pyrimidine Derivatives
  申请人：Altenbach Robert J.

  公开号：US20080188452A1

  公开（公告）日：2008-08-07

  Macrocyclic benzofused pyrimidine compounds, compositions comprising such compounds, methods for making the compounds, and methods of treating and preventing the progression of diseases, conditions and disorders using such compounds and compositions are described herein.

  本文描述了大环苯并嘧啶化合物、包含这种化合物的组合物、制备这种化合物的方法，以及使用这种化合物和组合物治疗和预防疾病、病症和障碍的方法。
• US8735411B2
  申请人：——

  公开号：US8735411B2

  公开（公告）日：2014-05-27