(2-adamantan-1-yl-4-oxo-4H-chromen-6-yl)oxoacetic acid methyl ester | 750572-67-9

• 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: (2-adamantan-1-yl-4-oxo-4H-chromen-6-yl)oxoacetic acid methyl ester
• 英文别名: Methyl 2-[2-(1-adamantyl)-4-oxochromen-6-yl]-2-oxoacetate
• CAS: 750572-67-9
• 化学式: C₂₂H₂₂O₅
• 分子量: 366.414
• InChiKey: VCMKSHQZLNWRNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  (2-adamantan-1-yl-4-oxo-4H-chromen-6-yl)oxoacetic acid methyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 以90%的产率得到(2-Adamantan-1-yl-4-oxo-4H-chromen-6-yl)-oxo-acetic 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-acetyl-4-hydroxyphenyl)acetic acid methyl ester 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 、 Amberlite IRA 900 carbonate form 、 potassium carbonate 、 二甲基亚砜 、 三乙胺 作用下， 以 甲酸 、 乙醇 、 二氯甲烷 、 异丙醇 、 甲苯 、 苯 为溶剂， 反应 67.75h， 生成 (2-adamantan-1-yl-4-oxo-4H-chromen-6-yl)oxoacetic acid methyl 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.