A-940894 | 1027330-82-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: A-940894
• 英文别名: 4-piperazin-1-yl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine；(4-(Piperazin-1-yl)-6,7-dihydro-5H-benzo(6,7)cyclohepta(1,2-d)pyrimidin-2-yl)amine；6-piperazin-1-yl-3,5-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2(7),3,5,11,13-hexaen-4-amine
• CAS: 1027330-82-0
• 化学式: C₁₇H₂₁N₅
• 分子量: 295.387
• InChiKey: KUZRWWLVBUPCRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  67.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  哌嗪 、 toluene-4-sulfonic acid 2-amino-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl ester 以 乙腈 为溶剂， 反应 16.0h， 以60%的产率得到A-940894
  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

• Method for Pain Treatment
  申请人：Cowart Marlon D.

  公开号：US20080194538A1

  公开（公告）日：2008-08-14

  This invention discloses a method of treating pain by administering histamine H 4 receptor ligands and compositions comprising the same.

  这项发明揭示了一种通过给予组织胺H4受体配体和包含相同的组合物来治疗疼痛的方法。
• 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。
• Selective Histamine H4 Receptor Antagonists for the Treatment of Vestibular Disorders
  申请人：Desmadryl Gilles

  公开号：US20120039913A1

  公开（公告）日：2012-02-16

  The invention relates to Histamine H4 receptor antagonists or inhibitors of Histamine H4 receptor gene expression for the treatment and/or the prevention of vestibular disorders.

  该发明涉及组胺H4受体拮抗剂或组胺H4受体基因表达抑制剂，用于治疗和/或预防前庭障碍。
• SELECTIVE HISTAMINE H4 RECEPTOR ANTAGONISTS FOR THE TREATMENT OF VESTIBULAR DISORDERS
  申请人：INSERM (Institut National de la Santé et de la Recherche Médicale)

  公开号：EP3130376A1

  公开（公告）日：2017-02-15

  The invention relates to Histamine H4 receptor antagonists or inhibitors of Histamine H4 receptor gene expression for the treatment and/or the prevention of vestibular disorders.

  本发明涉及组胺 H4 受体拮抗剂或组胺 H4 受体基因表达抑制剂，用于治疗和/或预防前庭失调。
• Selective histamine H4 receptor antagonists for the treatment of vestibular disorders
  申请人：INSERM (Institut National de la Sante de la Recherche Medicale)

  公开号：US10195195B2

  公开（公告）日：2019-02-05

  The invention relates to Histamine H4 receptor antagonists or inhibitors of Histamine H4 receptor gene expression for the treatment and/or the prevention of vestibular disorders.

  本发明涉及组胺 H4 受体拮抗剂或组胺 H4 受体基因表达抑制剂，用于治疗和/或预防前庭失调。