adamantane-1-carboxylic acid 2-acetyl-4-(methoxycarbonyl)phenyl ester | 750572-54-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: adamantane-1-carboxylic acid 2-acetyl-4-(methoxycarbonyl)phenyl ester
• 英文别名: (2-Acetyl-4-methoxycarbonylphenyl) adamantane-1-carboxylate
• CAS: 750572-54-4
• 化学式: C₂₁H₂₄O₅
• 分子量: 356.419
• InChiKey: HSKGJYUCVAHJEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  adamantane-1-carboxylic acid 2-acetyl-4-(methoxycarbonyl)phenyl ester 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲酸 、 异丙醇 为溶剂， 反应 5.75h， 生成 2-(1-adamantyl)-4-chromenone-6-carboxylic acid
  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：

  3-乙酰基-4-羟基苯甲酸甲酯 、 金刚烷酰氯 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 18.0h， 以99%的产率得到adamantane-1-carboxylic acid 2-acetyl-4-(methoxycarbonyl)phenyl ester
  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

文献信息

• 2-(1-Adamantyl)-4-(thio)chromenone-6-carboxylic Acids:  Potent Reversible Inhibitors of Human Steroid Sulfatase
  作者：Amarylla Horvath、Peter Nussbaumer、Barbara Wolff、Andreas Billich

  DOI：10.1021/jm0407916

  日期：2004.8.1

  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.