(3'-methoxy-[1,1'-biphenyl]-4-yl)(pyridin-4-yl)methanone | 1233693-06-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3'-methoxy-[1,1'-biphenyl]-4-yl)(pyridin-4-yl)methanone
• 英文别名: (3'-methoxybiphenyl-4-yl)(pyridin-4-yl)methanone；[4-(3-methoxyphenyl)phenyl]-pyridin-4-ylmethanone
• CAS: 1233693-06-5
• 化学式: C₁₉H₁₅NO₂
• 分子量: 289.334
• InChiKey: CRYLFDKSRAEOMJ-UHFFFAOYSA-N

物化性质

• 沸点：
  465.1±30.0 °C(Predicted)
• 密度：
  1.157±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 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：
  3

反应信息

• 作为反应物：
  描述：

  (3'-methoxy-[1,1'-biphenyl]-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84%的产率得到4-[(3'-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-氯甲基吡啶 在 aluminum (III) chloride 、 四丁基溴化铵 、 palladium diacetate 、 sodium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 26.08h， 生成 (3'-methoxy-[1,1'-biphenyl]-4-yl)(pyridin-4-yl)methanone
  参考文献：
  名称：

  NOVEL CYTOCHROME P450 INHIBITORS AND THEIR METHOD OF USE

  摘要：

  本发明实施例涉及一种新型细胞色素P450抑制剂及其药物组合物，具有改变疾病作用，用于治疗与皮质醇过度产生相关的疾病，包括代谢综合征和任何涉及皮质醇过度产生的疾病。

  公开号：

  US20150210641A1

文献信息

• 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.
• [EN] NOVEL CYTOCHROME P450 INHIBITORS AND THEIR METHOD OF USE<br/>[FR] NOUVEAUX INHIBITEURS DU CYTOCHROME P450 ET LEUR MÉTHODE D'UTILISATION
  申请人：CORTENDO AB PUBL

  公开号：WO2015112369A1

  公开（公告）日：2015-07-30

  Embodiments of the present invention relate to novel cytochrome P450 inhibitors and pharmaceutical compositions thereof having a disease-modifying action in the treatment of diseases associated with the overproduction of Cortisol that include metabolic syndrome, and any involving the overproduction of Cortisol.
• 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.
• NOVEL CYTOCHROME P450 INHIBITORS AND THEIR METHOD OF USE
  申请人：CORTENDO AB (PUBL)

  公开号：US20150210641A1

  公开（公告）日：2015-07-30

  Embodiments of the present invention relate to novel cytochrome P450 inhibitors and pharmaceutical compositions thereof having a disease-modifying action in the treatment of diseases associated with the overproduction of cortisol that include metabolic syndrome, and any involving the overproduction of cortisol.

  本发明实施例涉及一种新型细胞色素P450抑制剂及其药物组合物，具有改变疾病作用，用于治疗与皮质醇过度产生相关的疾病，包括代谢综合征和任何涉及皮质醇过度产生的疾病。