6-acetyl-2-adamantan-1-ylchromen-4-one | 750572-63-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-acetyl-2-adamantan-1-ylchromen-4-one
• 英文别名: 6-Acetyl-2-(1-adamantyl)chromen-4-one
• CAS: 750572-63-5
• 化学式: C₂₁H₂₂O₃
• 分子量: 322.404
• InChiKey: OUNAEXHTZWUHST-UHFFFAOYSA-N

物化性质

• 熔点：
  183-185 °C
• 沸点：
  491.2±45.0 °C(Predicted)
• 密度：
  1.266±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-acetyl-2-adamantan-1-ylchromen-4-one 在 溴 、 溶剂黄146 作用下， 反应 3.0h， 以68%的产率得到2-adamantan-1-yl-6-(2-bromoacetyl)chromen-4-one
  参考文献：
  名称：

  2-(1-Adamantyl)-4-(thio)chromenone-6-carboxylic Acids:  Potent Reversible Inhibitors of Human Steroid Sulfatase

  摘要：

  Steroid sulfatase (STS) is an attractive target for the potential therapy of a number of estrogen- and androgen-dependent disorders. Most potent STS inhibitors known so far act as irreversible enzyme blockers and feature an aryl sulfamate moiety; even minor modifications at the sulfamate group result in drastically decreased activity. On the basis of a recently reported subclass of highly potent STS inhibitors, i.e., chromenone sulfamates, we now extended the investigation of structure-activity relationships to hitherto unstudied sulfamate replacements. Thereby, we discovered 2-(1-adamantyl)-4-(thio)chromenone-6-carboxylic acids (5d and 5j) as potent, reversible inhibitors of STS. In a cell-free system using purified human STS, both new inhibitors show similar K-i values (0.50 muM and 0.53 muM, respectively). However, the thio analogue 5j is superior to 5d (IC50 = 0.18 muM versus 9.4 muM) in a cellular assay system using CHO cells overexpressing STS. Compound 5j is an example of a reversible STS inhibitor with potent activity toward the target enzyme in a cellular test system. Moreover, 5d,j are stable and have no estrogenic potential.

  DOI：

  10.1021/jm0407916
• 作为产物：
  描述：

  2-羟基-5-甲基苯乙酮 在 吡啶 、 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 草酰氯 、 偶氮二异丁腈 、 potassium acetate 、 potassium carbonate 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 甲酸 、 乙醚 、 二氯甲烷 、 异丙醇 、 苯 为溶剂， 反应 35.25h， 生成 6-acetyl-2-adamantan-1-ylchromen-4-one
  参考文献：
  名称：

  2-(1-Adamantyl)-4-(thio)chromenone-6-carboxylic Acids:  Potent Reversible Inhibitors of Human Steroid Sulfatase

  摘要：

  Steroid sulfatase (STS) is an attractive target for the potential therapy of a number of estrogen- and androgen-dependent disorders. Most potent STS inhibitors known so far act as irreversible enzyme blockers and feature an aryl sulfamate moiety; even minor modifications at the sulfamate group result in drastically decreased activity. On the basis of a recently reported subclass of highly potent STS inhibitors, i.e., chromenone sulfamates, we now extended the investigation of structure-activity relationships to hitherto unstudied sulfamate replacements. Thereby, we discovered 2-(1-adamantyl)-4-(thio)chromenone-6-carboxylic acids (5d and 5j) as potent, reversible inhibitors of STS. In a cell-free system using purified human STS, both new inhibitors show similar K-i values (0.50 muM and 0.53 muM, respectively). However, the thio analogue 5j is superior to 5d (IC50 = 0.18 muM versus 9.4 muM) in a cellular assay system using CHO cells overexpressing STS. Compound 5j is an example of a reversible STS inhibitor with potent activity toward the target enzyme in a cellular test system. Moreover, 5d,j are stable and have no estrogenic potential.

  DOI：

  10.1021/jm0407916