1-{6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-2-naphthyl}-1-ethanone | 247173-59-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-{6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-2-naphthyl}-1-ethanone
• 英文别名: 1-{6-[1-Hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]naphthalen-2-yl}-1-ethanone；1-[6-[1-hydroxy-1-(1H-imidazol-5-yl)-2-methylpropyl]naphthalen-2-yl]ethanone
• CAS: 247173-59-7
• 化学式: C₁₉H₂₀N₂O₂
• 分子量: 308.38
• InChiKey: HVVULDASPWETLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,6-二溴萘 在 正丁基锂 、 吡啶盐酸盐 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， 反应 5.0h， 生成 1-{6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-2-naphthyl}-1-ethanone
  参考文献：
  名称：

  17,20-Lyase inhibitors. Part 4: Design, synthesis and structure–activity relationships of naphthylmethylimidazole derivatives as novel 17,20-lyase inhibitors

  摘要：

  A novel series of naphthylmethylimidazole derivatives and related compounds have been investigated as selective 17,20-lyase inhibitors. Optimization of the substituent at the 6-position on the naphthalene ring was performed to yield a methylcarbamoyl derivative, which exhibited potent inhibitory activity against human 17,20-lyase and promising selectivity (> 200-fold) for 17,20-lyase over CYP3A4. Further modifications of the methylcarbamoyl derivative led to the discovery of the corresponding tricyclic compound, which showed highly potent activity against human 17,20-lyase (IC50 19 nM) and good selectivity (> 1000-fold) for inhibition of 17,20-lyase over CYP3A4. Additional biological evaluation revealed that the tricyclic compound had potent in vivo efficacy in monkeys and favorable pharmacokinetic profiles when administered in rats. Asymmetric synthesis of the selective tricyclic inhibitor was also achieved using a chiral alpha-hydroxy ketone. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.017

文献信息

• Naphthalene derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06573289B1

  公开（公告）日：2003-06-03

  A composition containing a compound of the formula: wherein A is a nitrogen-containing heterocyclic group which may be substituted, R1 is a hydrogen atom, hydrocarbon group which may be substituted, or monocyclic aromatic heterocyclic group which may be substituted, R2 is a hydrogen atom or a lower alkyl group which may be substituted, R3, R4, R5, R6, R7, R8 and R9 are independently a hydrogen atom, a hydrocarbon group which may be substituted, a hydroxy group which may be substituted, a thiol group which may be substituted, an amino group which may be substituted, an acyl group or a halogen atom, a salt thereof or a prodrug thereof has steroid C17,20-lyase inhibitory activity, and is useful for preventing and treating for example, primary cancer of malignant tumor, its metastasis and recurrence thereof.

  包含以下公式化合物的组合物： 其中A是可被取代的含氮杂环基团，R1是氢原子、可被取代的烃基团或可被取代的单环芳族杂环基团，R2是氢原子或可被取代的低级烷基团，R3、R4、R5、R6、R7、R8和R9独立地是氢原子、可被取代的烃基团、可被取代的羟基、可被取代的硫醇基、可被取代的氨基、酰基或卤素原子，其盐或前药对类固醇C17,20-裂解酶具有抑制作用，并且对于例如预防治疗原发恶性肿瘤、其转移和复发等是有用的。
• NAPHTHALENE DERIVATIVES, THEIR PRODUCTION AND USE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1073640B1

  公开（公告）日：2005-04-13
• US6573289B1
  申请人：——

  公开号：US6573289B1

  公开（公告）日：2003-06-03
• US7084149B2
  申请人：——

  公开号：US7084149B2

  公开（公告）日：2006-08-01
• [EN] NAPHTHALENE DERIVATIVES, THEIR PRODUCTION AND USE<br/>[FR] DERIVES DE NAPHTALENE, LEUR PRODUCTION ET UTILISATION
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：WO1999054309A1

  公开（公告）日：1999-10-28

  (EN) A composition containing a compound of formula (I) wherein A is a nitrogen-containing heterocyclic group which may be substituted, R1 is a hydrogen atom, hydrocarbon group which may be substituted, or monocyclic aromatic heterocyclic group which may be substituted, R2 is a hydrogen atom or a lower alkyl group which may be substituted, R3, R4, R5, R6, R7, R8 and R9 are independently a hydrogen atom, a hydrocarbon group which may be substituted, a hydroxy group which may be substituted, a thiol group which may be substituted, an amino group which may be substituted, an acyl group or a halogen atom, a salt thereof or a prodrug thereof, has steroid C17,20-lyase inhibitory activity, and are useful for preventing and treating a mammal suffering from, for example, primary cancer of malignant tumor, its metastasis and recurrence thereof.(FR) L'invention concerne une composition contenant un composé de la formule (I) dans laquelle A représente un groupe hétérocyclique contenant de l'azote lequel peut être substitué, R1 représente un atome d'hydrogène, un groupe hydrocarbure pouvant être substitué, ou un groupe hétérocyclique aromatique monocyclique pouvant être substitué, R2 représente un atome d'hydrogène ou un groupe alkyle inférieur pouvant être substitué, R3, R4, R5, R6, R7, R8 et R9 représentent indépendamment un atome d'hydrogène, un groupe hydrocarbure pouvant être substitué, un groupe hydroxy pouvant être substitué, un groupe thiol pouvant être substitué, un groupe amino pouvant être substitué, un groupe acyle ou un atome d'halogène, un sel de ceux-ci ou un promédicament de ceux-ci, laquelle composition présente une activité inhibitrice de la lyase -C17,20 stéroïde, et sont utiles dans la prévention et le traitement d'un mammifère souffrant, par exemple, d'un cancer primitif à tumeur maligne, sa métastase et sa récurrence.