1-cyclohexyl-1,1-bis(4-hydroxyphenyl)methanol | 721458-01-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-cyclohexyl-1,1-bis(4-hydroxyphenyl)methanol
• 英文别名: 4-[Cyclohexyl-hydroxy-(4-hydroxyphenyl)methyl]phenol；4-[cyclohexyl-hydroxy-(4-hydroxyphenyl)methyl]phenol
• CAS: 721458-01-1
• 化学式: C₁₉H₂₂O₃
• 分子量: 298.382
• InChiKey: PZNGLNFEVAFPOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-cyclohexyl-1,1-bis(4-hydroxyphenyl)methanol 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 、 甲苯 为溶剂， 反应 2.0h， 以52%的产率得到[4-[Cyclohexyl-hydroxy-(4-sulfamoyloxyphenyl)methyl]phenyl] sulfamate
  参考文献：
  名称：

  Synthesis, in vitro and in vivo activity of benzophenone-based inhibitors of steroid sulfatase

  摘要：

  Steroid sulfatase (STS) is all important new therapeutic target in oncology. Attempts to design nonsteroidal STS inhibitors, because of the oestrogenicity of the original lead oestrone 3-O-sulfamate in rodents, have led to the discovery of benzophenone-4,4'-O,O-bis-sulfamate (BENZOMATE, 3). The nonfused bicyclic BENZOMATE is a highly potent STS inhibitor in vitro, inhibiting STS activity in intact MCF-7 breast cancer cells by >70% at 0.1 muM and in placental microsomes by >98% at 10 mum. When MCF-7 cells were pre-treated with 3 at 1 muM and then washed to remove unbound inhibitor, the initial 94% inhibition was reduced to 89% suggesting that 3, like other sulfamate-based STS inhibitors, inhibits the enzyme irreversibly. This agent also inhibits rat liver STS activity by 84% and 93% respectively 24 h after a single dose of 1 or 10 mg/kg, demonstrating that BENZOMATE possesses similar in Vivo potency to the established potent nonsteroidal inhibitor 667COUMATE. Several modifications were made to BENZOMATE structurally and effects on in vitro activity were examined. These structure-activity relationship studies show that its carbonyl and bis-sulfamate groups are pivotal for activity, although conformational flexibility is not required. Two rigid anthraquinone-based sulfamate derivatives however showed inhibitory activity significantly better than BENZOMATE in the MCF-7 cell assay. BENZOMATE and related analogues therefore represent all important class of non-steroidal STS inhibitor and lead compounds for future drug design. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.040
• 作为产物：
  描述：

  4,4'-二羟基二苯甲酮 在 咪唑 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1-cyclohexyl-1,1-bis(4-hydroxyphenyl)methanol
  参考文献：
  名称：

  Synthesis, in vitro and in vivo activity of benzophenone-based inhibitors of steroid sulfatase

  摘要：

  Steroid sulfatase (STS) is all important new therapeutic target in oncology. Attempts to design nonsteroidal STS inhibitors, because of the oestrogenicity of the original lead oestrone 3-O-sulfamate in rodents, have led to the discovery of benzophenone-4,4'-O,O-bis-sulfamate (BENZOMATE, 3). The nonfused bicyclic BENZOMATE is a highly potent STS inhibitor in vitro, inhibiting STS activity in intact MCF-7 breast cancer cells by >70% at 0.1 muM and in placental microsomes by >98% at 10 mum. When MCF-7 cells were pre-treated with 3 at 1 muM and then washed to remove unbound inhibitor, the initial 94% inhibition was reduced to 89% suggesting that 3, like other sulfamate-based STS inhibitors, inhibits the enzyme irreversibly. This agent also inhibits rat liver STS activity by 84% and 93% respectively 24 h after a single dose of 1 or 10 mg/kg, demonstrating that BENZOMATE possesses similar in Vivo potency to the established potent nonsteroidal inhibitor 667COUMATE. Several modifications were made to BENZOMATE structurally and effects on in vitro activity were examined. These structure-activity relationship studies show that its carbonyl and bis-sulfamate groups are pivotal for activity, although conformational flexibility is not required. Two rigid anthraquinone-based sulfamate derivatives however showed inhibitory activity significantly better than BENZOMATE in the MCF-7 cell assay. BENZOMATE and related analogues therefore represent all important class of non-steroidal STS inhibitor and lead compounds for future drug design. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.040

文献信息

• Oestrogen-17-sulphamates as inhibitors of steroid sulphatase
  申请人：Lloyd Potter Victor Barry

  公开号：US20060281719A1

  公开（公告）日：2006-12-14

  There is provided a compound of Formula I wherein X is a ring system; R 1 is any one of a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group; R 2 is any one of a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group; wherein when X is a steroidal structure and both of R 1 and R 2 are sulphamate groups, the steroidal ring system (X) represents an oestrogen; and wherein said compound is capable of inhibiting steroid sulphatase (STS) activity and/or is capable of acting as a modulator of cell cycling and/or as a modulator of apoptosis and/or as a modulator of cell growth. There is also provided a compound of Formula VIII wherein R 2 is any one of a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group; and wherein said compound is capable of inhibiting steroid sulphatase (STS) activity and/or is capable of acting as a modulator of cell cycling and/or as a modulator of apoptosis and/or as a modulator of cell growth.

  提供了一种化合物，其化学式为I，其中X是一个环系统；R1是磺酰胺基团、膦酸酯基团、硫代膦酸酯基团、磺酸基团或磺酰胺基团之一；R2是磺酰胺基团、膦酸酯基团、硫代膦酸酯基团、磺酸基团或磺酰胺基团之一；其中当X是类固醇结构且R1和R2均为磺酰胺基团时，类固醇环系统（X）表示雌激素；该化合物能够抑制类固醇硫酸酯酶（STS）活性并/或能够作为细胞周期调节剂、凋亡调节剂和/或细胞生长调节剂。还提供了一种化合物，其化学式为VIII，其中R2是磺酰胺基团、膦酸酯基团、硫代膦酸酯基团、磺酸基团或磺酰胺基团之一；该化合物能够抑制类固醇硫酸酯酶（STS）活性并/或能够作为细胞周期调节剂、凋亡调节剂和/或细胞生长调节剂。
• US7119081B2
  申请人：——

  公开号：US7119081B2

  公开（公告）日：2006-10-10
• US8030296B2
  申请人：——

  公开号：US8030296B2

  公开（公告）日：2011-10-04