4-(6-(3,4-difuorophenyl)-3,4-dihydronaphthalen-1-yl)pyridine hydrochloride | 1051380-41-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-(6-(3,4-difuorophenyl)-3,4-dihydronaphthalen-1-yl)pyridine hydrochloride
• 英文别名: 4-(6-(3,4-difluorophenyl)-3,4-dihydronaphthalen-1-yl)pyridine hydrochloride；4-[6-(3,4-Difluorophenyl)-3,4-dihydronaphthalen-1-yl]pyridine;hydrochloride
• CAS: 1051380-41-6
• 化学式: C₂₁H₁₅F₂N*ClH
• 分子量: 355.815
• InChiKey: MCXOBRFKSNUMRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.83
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  12.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(6-(3,4-difuorophenyl)-3,4-dihydronaphthalen-1-yl)pyridine hydrochloride 在 palladium hydroxide on carbon 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 以98%的产率得到4-(6-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)pyridine hydrochloride
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Molecular Modeling of Abiraterone Analogues: Novel CYP17 Inhibitors for the Treatment of Prostate Cancer

  摘要：

  Abiraterone, a steroidal cytochrome P450 17alpha-hydroxylase-17,20-lyase inhibitor (CYP17), is currently undergoing phase II clinical trials as a potential drug for the treatment of androgen-dependent prostate cancer. Since steroidal compounds often show side effects attributable to their structure, we have tried to replace the sterane scaffold by nonsteroidal core structures. The design and synthesis of 20 new abiraterone mimetics are described. Their activities have been tested with recombinant human CYP17 expressed in E. coli. Promising compounds were further evaluated for selectivity against CYP11B1, CYP11B2, and the hepatic CYP3A4. Compounds 19 and 20 showed comparable activity to abiraterone (IC50 values of 144 and 64 nM vs 72 nM) and similar or even better selectivity against the other CYP enzymes. Selected compounds were also docked into our homology model, and the same binding modes as for abiraterone were found.

  DOI：

  10.1021/jm800355c
• 作为产物：
  描述：

  6-(3,4-difluorophenyl)-1-(pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-ol 在 盐酸 作用下， 以 异丙醇 为溶剂， 反应 2.0h， 以98%的产率得到4-(6-(3,4-difuorophenyl)-3,4-dihydronaphthalen-1-yl)pyridine hydrochloride
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Molecular Modeling of Abiraterone Analogues: Novel CYP17 Inhibitors for the Treatment of Prostate Cancer

  摘要：

  Abiraterone, a steroidal cytochrome P450 17alpha-hydroxylase-17,20-lyase inhibitor (CYP17), is currently undergoing phase II clinical trials as a potential drug for the treatment of androgen-dependent prostate cancer. Since steroidal compounds often show side effects attributable to their structure, we have tried to replace the sterane scaffold by nonsteroidal core structures. The design and synthesis of 20 new abiraterone mimetics are described. Their activities have been tested with recombinant human CYP17 expressed in E. coli. Promising compounds were further evaluated for selectivity against CYP11B1, CYP11B2, and the hepatic CYP3A4. Compounds 19 and 20 showed comparable activity to abiraterone (IC50 values of 144 and 64 nM vs 72 nM) and similar or even better selectivity against the other CYP enzymes. Selected compounds were also docked into our homology model, and the same binding modes as for abiraterone were found.

  DOI：

  10.1021/jm800355c

文献信息

• Synthesis, Biological Evaluation, and Molecular Modeling of Abiraterone Analogues: Novel CYP17 Inhibitors for the Treatment of Prostate Cancer
  作者：Mariano A. E. Pinto-Bazurco Mendieta、Matthias Negri、Carsten Jagusch、Ursula Müller-Vieira、Thomas Lauterbach、Rolf W. Hartmann

  DOI：10.1021/jm800355c

  日期：2008.8.1

  Abiraterone, a steroidal cytochrome P450 17alpha-hydroxylase-17,20-lyase inhibitor (CYP17), is currently undergoing phase II clinical trials as a potential drug for the treatment of androgen-dependent prostate cancer. Since steroidal compounds often show side effects attributable to their structure, we have tried to replace the sterane scaffold by nonsteroidal core structures. The design and synthesis of 20 new abiraterone mimetics are described. Their activities have been tested with recombinant human CYP17 expressed in E. coli. Promising compounds were further evaluated for selectivity against CYP11B1, CYP11B2, and the hepatic CYP3A4. Compounds 19 and 20 showed comparable activity to abiraterone (IC50 values of 144 and 64 nM vs 72 nM) and similar or even better selectivity against the other CYP enzymes. Selected compounds were also docked into our homology model, and the same binding modes as for abiraterone were found.