6-hydroxy-2-adamantan-2-ylidenemethylbenzoxazole | 340705-44-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 6-hydroxy-2-adamantan-2-ylidenemethylbenzoxazole
• 英文别名: 2-(adamantan-2-ylidenemethyl)benzoxazol-6-ol
• CAS: 340705-44-4
• 化学式: C₁₈H₁₉NO₂
• 分子量: 281.354
• InChiKey: CEAARYLECHJRSD-DHDCSXOGSA-N

物化性质

• 沸点：
  475.0±37.0 °C(predicted)
• 密度：
  1.303±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.37
• 重原子数：
  21.0
• 可旋转键数：
  1.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.26
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  6-hydroxy-2-adamantan-2-ylidenemethylbenzoxazole 在 2,6-二叔丁基-4-甲基吡啶 、 氨基磺酰氯 作用下， 以 二氯甲烷 为溶剂， 以88%的产率得到sulfamic acid 2-(adamantan-2-ylidenemethyl)benzoxazol-6-yl ester
  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：

  6-羟基-2-甲基苯并恶唑 在 sodium hexamethyldisilazane 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 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

文献信息

• Estrone formate: a novel type of irreversible inhibitor of human steroid sulfatase
  作者：Erwin P. Schreiner、Andreas Billich

  DOI：10.1016/j.bmcl.2004.07.013

  日期：2004.10

  inhibition of human steroid sulfatase (STS). Among the carbamate (6), thiocarbamate (8), cyanate (7), formate (9), and acetate (10) analogs of estrone, only 9 was found to inhibit STS in a time- and concentration-dependent manner. With an IC(50) of 0.42 microM 9 is the first potent inactivator of STS which does not feature the sulfamate group. Furthermore a formate-type inhibitor featuring a benzoxazole

  已经制备了一系列类型为雌酮-3-OC（O，S）-X的雌酮缀合物，并评估了其对人类固醇硫酸酯酶（STS）的抑制作用。在雌酮的氨基甲酸酯（6），硫代氨基甲酸酯（8），氰酸酯（7），甲酸酯（9）和乙酸酯（10）类似物中，仅9种以时间和浓度依赖性方式抑制STS。IC（50）为0.42 microM 9是STS的第一种有效的灭活剂，它不具有氨基磺酸盐基团。此外，制备了以苯并恶唑部分代替类固醇骨架为特征的甲酸酯型抑制剂（14），表明甲酸酯基团具有灭活的一般原理。作为作用方式，我们建议甲酰基部分立即转移至STS活性位点的亲核残基。
• 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.