4-((spiro[1,3-dioxolane-2,1'-indane]-5'-yl)methylene)-1-methylpiperidine | 940941-03-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 4-((spiro[1,3-dioxolane-2,1'-indane]-5'-yl)methylene)-1-methylpiperidine
• 英文别名: 1-Methyl-4-(spiro[1,3-dioxolane-2,1'-2,3-dihydroindene]-5'-ylmethylidene)piperidine
• CAS: 940941-03-7
• 化学式: C₁₈H₂₃NO₂
• 分子量: 285.386
• InChiKey: GIPRGLNANNLQSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-((spiro[1,3-dioxolane-2,1'-indane]-5'-yl)methylene)-1-methylpiperidine 在 palladium on activated charcoal 氢气 、 对甲苯磺酸 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 20.0 ℃ 、413.7 kPa 条件下， 反应 3.0h， 生成 5-((1-methylpiperidin-4-yl)methyl)indan-1-one
  参考文献：
  名称：

  1,4-Dihydroindeno[1,2-c]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel

  摘要：

  The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 mu M in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.

  DOI：

  10.1021/jm061223o
• 作为产物：
  描述：

  2,3-dihydrospiro[indene-1,2'-[1,3]dioxolane]-5-carbaldehyde 在 sodium tetrahydroborate 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 1.75h， 生成 4-((spiro[1,3-dioxolane-2,1'-indane]-5'-yl)methylene)-1-methylpiperidine
  参考文献：
  名称：

  1,4-Dihydroindeno[1,2-c]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel

  摘要：

  The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 mu M in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.

  DOI：

  10.1021/jm061223o