(3'-fluoro-4'-methoxybiphenyl-4-yl)(pyridin-4-yl)methanone | 1233693-07-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3'-fluoro-4'-methoxybiphenyl-4-yl)(pyridin-4-yl)methanone
• 英文别名: [4-(3-Fluoro-4-methoxyphenyl)phenyl]-pyridin-4-ylmethanone
• CAS: 1233693-07-6
• 化学式: C₁₉H₁₄FNO₂
• 分子量: 307.324
• InChiKey: NAAHSRWXSZNOHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3'-fluoro-4'-methoxybiphenyl-4-yl)(pyridin-4-yl)methanone 在 氢氧化钾 、 一水合肼 作用下， 以 乙二醇 为溶剂， 以91%的产率得到4-[(3'-fluoro-4'-methoxybiphenyl-4-yl)methyl]pyridine
  参考文献：
  名称：

  Replacement of Imidazolyl by Pyridyl in Biphenylmethylenes Results in Selective CYP17 and Dual CYP17/CYP11B1 Inhibitors for the Treatment of Prostate Cancer

  摘要：

  Androgens are well-known to stimulate prostate cancer (PC) growth. Thus, blockade of androgen production in testes and adrenals by CYP17 inhibition is a promising strategy for the treatment of PC. Moreover, many PC patients suffer from glucocorticoid overproduction, and importantly mutated androgen receptors can be stimulated by glucocorticoids. In this study, the first dual inhibitor of CYP17 and CYP11B1 (the enzyme responsible for the last step in glucocorticoid biosynthesis) is described. A series of biphenylmethylene pyridines has been designed, synthesized, and tested as CYP17 and CYP11B1 inhibitors. The most active compounds were also tested for selectivity against CYP11B2 (aldosterone synthase), CYP19 (aromatase), and hepatic CYP3A4. In detail, compound 6 was identified as a dual inhibitor of CYP17/CYP11B1 (IC50 values of 226 and 287 nM) showing little inhibition of the other enzymes as well as compound 9 as a selective, highly potent CYP17 inhibitor (IC50 = 52 nM) exceeding abiraterone in terms of activity and selectivity.

  DOI：

  10.1021/jm100317b
• 作为产物：
  描述：

  (4-溴苯基)-吡啶-4-基甲酮 、 3-氟-4-甲氧基苯硼酸 在 四丁基溴化铵 、 palladium diacetate 、 sodium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 4.0h， 以82%的产率得到(3'-fluoro-4'-methoxybiphenyl-4-yl)(pyridin-4-yl)methanone
  参考文献：
  名称：

  Isopropylidene Substitution Increases Activity and Selectivity of Biphenylmethylene 4-Pyridine Type CYP17 Inhibitors

  摘要：

  GYP 17 inhibition is a promising therapy for prostate cancer (PC) because proliferation of 80% of PC depends on androgen stimulation. Introduction of isopropylidene substituents onto the linker of biphenylmethylene 4-pyridines resulted in several strong GYP 17 inhibitors, which were more potent and selective, regarding GYP 11B1, 11B2, 19 and 3A4, than the drug candidate abiraterone.

  DOI：

  10.1021/jm100400a

文献信息

• Replacement of Imidazolyl by Pyridyl in Biphenylmethylenes Results in Selective CYP17 and Dual CYP17/CYP11B1 Inhibitors for the Treatment of Prostate Cancer
  作者：Qingzhong Hu、Carsten Jagusch、Ulrike E. Hille、Jörg Haupenthal、Rolf W. Hartmann

  DOI：10.1021/jm100317b

  日期：2010.8.12

  Androgens are well-known to stimulate prostate cancer (PC) growth. Thus, blockade of androgen production in testes and adrenals by CYP17 inhibition is a promising strategy for the treatment of PC. Moreover, many PC patients suffer from glucocorticoid overproduction, and importantly mutated androgen receptors can be stimulated by glucocorticoids. In this study, the first dual inhibitor of CYP17 and CYP11B1 (the enzyme responsible for the last step in glucocorticoid biosynthesis) is described. A series of biphenylmethylene pyridines has been designed, synthesized, and tested as CYP17 and CYP11B1 inhibitors. The most active compounds were also tested for selectivity against CYP11B2 (aldosterone synthase), CYP19 (aromatase), and hepatic CYP3A4. In detail, compound 6 was identified as a dual inhibitor of CYP17/CYP11B1 (IC50 values of 226 and 287 nM) showing little inhibition of the other enzymes as well as compound 9 as a selective, highly potent CYP17 inhibitor (IC50 = 52 nM) exceeding abiraterone in terms of activity and selectivity.
• Isopropylidene Substitution Increases Activity and Selectivity of Biphenylmethylene 4-Pyridine Type CYP17 Inhibitors
  作者：Qingzhong Hu、Lina Yin、Carsten Jagusch、Ulrike E. Hille、Rolf W. Hartmann

  DOI：10.1021/jm100400a

  日期：2010.7.8

  GYP 17 inhibition is a promising therapy for prostate cancer (PC) because proliferation of 80% of PC depends on androgen stimulation. Introduction of isopropylidene substituents onto the linker of biphenylmethylene 4-pyridines resulted in several strong GYP 17 inhibitors, which were more potent and selective, regarding GYP 11B1, 11B2, 19 and 3A4, than the drug candidate abiraterone.