N-(2-amino-5-(1-methyl-1H-imidazol-4-yl)phenyl)-6-(2-oxo-1-oxa-3,8-diazaspiro[4.5]decan-8-yl)nicotinamide | 1538608-37-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-amino-5-(1-methyl-1H-imidazol-4-yl)phenyl)-6-(2-oxo-1-oxa-3,8-diazaspiro[4.5]decan-8-yl)nicotinamide
• 英文别名: N-[2-amino-5-(1-methylimidazol-4-yl)phenyl]-6-(2-oxo-1-oxa-3,8-diazaspiro[4.5]decan-8-yl)pyridine-3-carboxamide
• CAS: 1538608-37-5
• 化学式: C₂₃H₂₅N₇O₃
• 分子量: 447.497
• InChiKey: DSWYPLARVKNCBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(氨基甲基)-1-苄基哌啶-4-醇 在 盐酸 、 10 wt% Pd(OH)2 on carbon 、 氢气 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 丙醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 27.0h， 生成 N-(2-amino-5-(1-methyl-1H-imidazol-4-yl)phenyl)-6-(2-oxo-1-oxa-3,8-diazaspiro[4.5]decan-8-yl)nicotinamide
  参考文献：
  名称：

  Delayed and Prolonged Histone Hyperacetylation with a Selective HDAC1/HDAC2 Inhibitor

  摘要：

  The identification and in vitro and in vivo characterization of a potent SHI-1:2 are described. Kinetic analysis indicated that biaryl inhibitors exhibit slow binding kinetics in isolated HDAC1 and HDAC2 preparations. Delayed histone hyperacetylation and gene expression changes were also observed in cell culture, and histone acetylation was observed in vivo beyond disappearance of drug from plasma. In vivo studies further demonstrated that continuous target inhibition was well tolerated and efficacious in tumor-bearing mice, leading to tumor growth inhibition with either once-daily or intermittent administration.

  DOI：

  10.1021/ml4004233

文献信息

• Delayed and Prolonged Histone Hyperacetylation with a Selective HDAC1/HDAC2 Inhibitor
  作者：Joey L. Methot、Dawn Mampreian Hoffman、David J. Witter、Matthew G. Stanton、Paul Harrington、Christopher Hamblett、Phieng Siliphaivanh、Kevin Wilson、Jed Hubbs、Richard Heidebrecht、Astrid M. Kral、Nicole Ozerova、Judith C. Fleming、Hongmei Wang、Alexander A. Szewczak、Richard E. Middleton、Bethany Hughes、Jonathan C. Cruz、Brian B. Haines、Melissa Chenard、Candia M. Kenific、Andreas Harsch、J. Paul Secrist、Thomas A. Miller

  DOI：10.1021/ml4004233

  日期：2014.4.10

  The identification and in vitro and in vivo characterization of a potent SHI-1:2 are described. Kinetic analysis indicated that biaryl inhibitors exhibit slow binding kinetics in isolated HDAC1 and HDAC2 preparations. Delayed histone hyperacetylation and gene expression changes were also observed in cell culture, and histone acetylation was observed in vivo beyond disappearance of drug from plasma. In vivo studies further demonstrated that continuous target inhibition was well tolerated and efficacious in tumor-bearing mice, leading to tumor growth inhibition with either once-daily or intermittent administration.