2-(adamantan-2-ylidene)-N-(2,4-dihydroxyphenyl)acetamide | 340706-03-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-(adamantan-2-ylidene)-N-(2,4-dihydroxyphenyl)acetamide
• CAS: 340706-03-8
• 化学式: C₁₈H₂₁NO₃
• 分子量: 299.37
• InChiKey: QGKPELNDXFFOQI-DHDCSXOGSA-N

物化性质

• 沸点：
  564.6±33.0 °C(predicted)
• 密度：
  1.395±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.42
• 重原子数：
  22.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  69.56
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-(adamantan-2-ylidene)-N-(2,4-dihydroxyphenyl)acetamide 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 以67%的产率得到6-hydroxy-2-adamantan-2-ylidenemethylbenzoxazole
  参考文献：
  名称：

  6-(2-Adamantan-2-ylidene-hydroxybenzoxazole)- O -sulfamate: A potent non-steroidal irreversible inhibitor of human steroid sulfatase

  摘要：

  We report the synthesis and results from the in vitro evaluation of 6-(adamantan-2-ylidene-hydroxybenzoxazole)-O-sulfamate 1 as an irreversible inhibitor of human steroid sulfatase (STS). Highly straightforward, condensation of 2-methyl-6-hydroxybenzoxazole with 2-adamantanone, subsequent elimination of water and sulfamoylation provide the title compound in 45% overall yield from the inexpensive 2,4-dihydroxyacetophenone. 1 was found to be a potent irreversible inhibitor of purified human steroid sulfatase (STS) and specific for this enzyme relative to human arylsulfatases A and B. In cellular assays with human keratinocytes, sebocytes and fibroblasts, 1 blocked STS activity with IC50 values in the range of 0.15-0.8 nM, and in MCF-7 breast cancer cells with IC50 = 2.3 nM, while it did not bind to estrogen receptors alpha and beta. Thus, 1 is a candidate for further investigation of its potential as a drug to be used in androgen- and estrogen-dependent diseases. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.050
• 作为产物：
  描述：

  2-(2-adamantylidene)acetic acid 在 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 生成 2-(adamantan-2-ylidene)-N-(2,4-dihydroxyphenyl)acetamide
  参考文献：
  名称：

  6-(2-Adamantan-2-ylidene-hydroxybenzoxazole)- O -sulfamate: A potent non-steroidal irreversible inhibitor of human steroid sulfatase

  摘要：

  We report the synthesis and results from the in vitro evaluation of 6-(adamantan-2-ylidene-hydroxybenzoxazole)-O-sulfamate 1 as an irreversible inhibitor of human steroid sulfatase (STS). Highly straightforward, condensation of 2-methyl-6-hydroxybenzoxazole with 2-adamantanone, subsequent elimination of water and sulfamoylation provide the title compound in 45% overall yield from the inexpensive 2,4-dihydroxyacetophenone. 1 was found to be a potent irreversible inhibitor of purified human steroid sulfatase (STS) and specific for this enzyme relative to human arylsulfatases A and B. In cellular assays with human keratinocytes, sebocytes and fibroblasts, 1 blocked STS activity with IC50 values in the range of 0.15-0.8 nM, and in MCF-7 breast cancer cells with IC50 = 2.3 nM, while it did not bind to estrogen receptors alpha and beta. Thus, 1 is a candidate for further investigation of its potential as a drug to be used in androgen- and estrogen-dependent diseases. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.050

文献信息

• Benzoxa- and benzthiazoles
  申请人：Novartis AG

  公开号：US06716865B1

  公开（公告）日：2004-04-06

  Benzoxa- and benzthiazoles substituted at the 2 position and carrying a sulfamic acid ester group bound via oxygen to the phenyl part of the ring structure, such as the compounds of formula (I) wherein the symbols have various significances, possess interesting pharmacological activity. They can be prepared by sulfamoylation of a corresponding compound carrying a hydroxy group on the phenyl part of the ring structure, or by N-substitution. They are indicated for use as steroid sulfatase inhibitors in the prevention and treatment of illnesses responsive to steroid sulfatase inhibition, such as acne.

  苯并噁唑和苯并噻唑在2位取代，并携带通过氧与环结构的苯基部分结合的磺酰胺酯基团，例如式(I)中的化合物，其中符号具有不同的意义，具有有趣的药理活性。它们可以通过对具有苯基环结构上羟基的相应化合物进行磺酰化或N-取代来制备。它们适用于作为类固醇磺酸酯酶抑制剂，用于预防和治疗对类固醇磺酸酯酶抑制敏感的疾病，如痤疮。
• BENZOXA-AND BENZOTHIAZOLYL SULFAMATES AND THEIR USE AS STEROID SULFATASE INHIBITORS
  申请人：Novartis AG

  公开号：EP1230227B1

  公开（公告）日：2004-06-23
• US6716865B1
  申请人：——

  公开号：US6716865B1

  公开（公告）日：2004-04-06
• [EN] BENZOXA- AND BENZTHIAZOLES<br/>[FR] BENZOXATHIAZOLES ET BENZTHIAZOLES
  申请人：NOVARTIS AG

  公开号：WO2001036398A1

  公开（公告）日：2001-05-25

  Benzoxa- and benzthiazoles substituted at the 2 position and carrying a sulfamic acid ester group bound via oxygen to the phenyl part of the ring structure, such as the compounds of formula (I) wherein the symbols have various significances, possess interesting pharmacological activity. They can be prepared by sulfamoylation of a corresponding compound carrying a hydroxy group on the phenyl part of the ring structure, or by N-substitution. They are indicated for use as steroid sulfatase inhibitors in the prevention and treatment of illnesses responsive to steroid sulfatase inhibition, such as acne.