(R)-1,4-dimethyl-6-(3-methylpiperazin-1-yl)phthalazine | 1095543-52-4

• 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: (R)-1,4-dimethyl-6-(3-methylpiperazin-1-yl)phthalazine
• 英文别名: 1,4-dimethyl-6-[(3R)-3-methylpiperazin-1-yl]phthalazine
• CAS: 1095543-52-4
• 化学式: C₁₅H₂₀N₄
• 分子量: 256.351
• InChiKey: PIHNOMGIZXZISQ-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  41
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  反式-1,2-环己二羧酸酐 、 (R)-1,4-dimethyl-6-(3-methylpiperazin-1-yl)phthalazine 、 1-氨基-1-环丙基腈盐酸盐 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 为溶剂， 以54%的产率得到(1R,2R)-N-(1-cyanocyclopropyl)-2-((R)-4-(1,4-dimethylphthalazin-6-yl)-2-methylpiperazine-1-carbonyl)cyclohexanecarboxamide
  参考文献：
  名称：

  Pharmacokinetic Benefits of 3,4-Dimethoxy Substitution of a Phenyl Ring and Design of Isosteres Yielding Orally Available Cathepsin K Inhibitors

  摘要：

  Rational structure-based design has yielded highly potent inhibitors of cathepsin K (Cat K) with excellent physical properties, selectivity profiles, and pharmacokinetics. Compounds with a 3,4-(CH3O)(2)Ph motif, such as 31, were found to have excellent metabolic stability and absorption profiles. Through metabolite identification studies, a reactive metabolite risk was identified with this motif: Subsequent structure-based design of isoteres culminated in the discovery of an optimized and balanced inhibitor (indazole, 38).

  DOI：

  10.1021/jm301119s
• 作为产物：
  描述：

  6-chloro-1,4-dimethylphthalazine 在 potassium tert-butylate 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 90.0h， 生成 (R)-1,4-dimethyl-6-(3-methylpiperazin-1-yl)phthalazine
  参考文献：
  名称：

  Pharmacokinetic Benefits of 3,4-Dimethoxy Substitution of a Phenyl Ring and Design of Isosteres Yielding Orally Available Cathepsin K Inhibitors

  摘要：

  Rational structure-based design has yielded highly potent inhibitors of cathepsin K (Cat K) with excellent physical properties, selectivity profiles, and pharmacokinetics. Compounds with a 3,4-(CH3O)(2)Ph motif, such as 31, were found to have excellent metabolic stability and absorption profiles. Through metabolite identification studies, a reactive metabolite risk was identified with this motif: Subsequent structure-based design of isoteres culminated in the discovery of an optimized and balanced inhibitor (indazole, 38).

  DOI：

  10.1021/jm301119s