8-(5-bromopyrimidm-4-yl)-1,4-dioxaspiro[4,5]decan-8-ol | 1289637-95-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 8-(5-bromopyrimidm-4-yl)-1,4-dioxaspiro[4,5]decan-8-ol
• 英文别名: 8-(5-Bromopyrimidin-4-yl)-1,4-dioxaspiro[4.5]decan-8-ol
• CAS: 1289637-95-1
• 化学式: C₁₂H₁₅BrN₂O₃
• 分子量: 315.167
• InChiKey: LYMIGWBRJDWTOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  64.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(5-bromopyrimidm-4-yl)-1,4-dioxaspiro[4,5]decan-8-ol 在 盐酸 、 palladium 10% on activated carbon 、 水 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 生成 4-hydroxy-4-(pyrimidin-4-yl)cyclohexanone
  参考文献：
  名称：

  Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist

  摘要：

  We report the identification of 13 (INCB3284) as a potent human CCR2 (hCCR2) antagonist. INCB3284 exhibited an IC50 of 3.7 nM in antagonism of monocyte chemoattractant protein-1 binding to hCCR2, an IC50 of 4.7 nM in antagonism of chemotaxis activity, an IC50 of 84 mu M in inhibition of the hERG potassium current, a free fraction of 58% in protein binding, high selectivity over other chemokine receptors and G-protein-coupled receptors, and acceptable oral bioavailability in rodents and primates. In human clinical trials, INCB3284 exhibited a pharmacokinetic profile suitable for once-a-day dosing (T-1/2 = 15 h).

  DOI：

  10.1021/ml200030q
• 作为产物：
  描述：

  5-溴嘧啶 、 1,4-环己二酮单乙二醇缩酮 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以20%的产率得到8-(5-bromopyrimidm-4-yl)-1,4-dioxaspiro[4,5]decan-8-ol
  参考文献：
  名称：

  Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist

  摘要：

  We report the identification of 13 (INCB3284) as a potent human CCR2 (hCCR2) antagonist. INCB3284 exhibited an IC50 of 3.7 nM in antagonism of monocyte chemoattractant protein-1 binding to hCCR2, an IC50 of 4.7 nM in antagonism of chemotaxis activity, an IC50 of 84 mu M in inhibition of the hERG potassium current, a free fraction of 58% in protein binding, high selectivity over other chemokine receptors and G-protein-coupled receptors, and acceptable oral bioavailability in rodents and primates. In human clinical trials, INCB3284 exhibited a pharmacokinetic profile suitable for once-a-day dosing (T-1/2 = 15 h).

  DOI：

  10.1021/ml200030q

文献信息

• Cycloalkyl Piperidine Tachykinin Receptor Antagonists
  申请人：DeVita Robert J.

  公开号：US20080153851A1

  公开（公告）日：2008-06-26

  The present invention is directed to certain piperidine compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

  本发明涉及某些哌啶类化合物，其可用作神经激肽-1（NK-1）受体拮抗剂，以及缓激肽和特别是物质P的抑制剂。本发明还涉及包含这些化合物作为活性成分的药物配方，以及这些化合物及其配方在治疗某些疾病，包括呕吐、尿失禁、抑郁症和焦虑症方面的使用。
• WO2006/57977
  申请人：——

  公开号：——

  公开（公告）日：——