3-(4-methoxybenzyl)naphthalen-2-ol | 1054315-09-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-(4-methoxybenzyl)naphthalen-2-ol
• 英文别名: 3-[(4-Methoxyphenyl)methyl]naphthalen-2-ol
• CAS: 1054315-09-1
• 化学式: C₁₈H₁₆O₂
• 分子量: 264.324
• InChiKey: WXYJZGWXKIQMJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-苯基双(三氟甲烷磺酰)亚胺 、 3-(4-methoxybenzyl)naphthalen-2-ol 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 以97%的产率得到3-(4-甲氧基苄基)萘-2-基三氟甲磺酸酯
  参考文献：
  名称：

  Novel Aldosterone Synthase Inhibitors with Extended Carbocyclic Skeleton by a Combined Ligand-Based and Structure-Based Drug Design Approach

  摘要：

  Pharmacophore modeling of a series of aldosterone synthase (CYP11B2) inhibitors triggered the design of compounds 11 and 12 by extending a previously established naphthalene molecular scaffold (e.g., present in molecules 1 and 2) via introduction of a phenyl or benzyl residue in 3-position. These additional aromatic moieties have been hypothesized to fit into the newly identified hydrophobic pharmacophore feature HY3. Subsequent docking studies in our refined CYP11B2 protein model have been performed prior to synthesis to estimate the inhibitory properties of the proposed molecules. While phenyl-substituted compound 11 (IC50 > 500 nM) did not dock under the given pharmacophore constraint (i.e., the Fe(heme)-N(ligand) interaction), benzyl-substituted compound 12 (IC50 = 154 nM) was found to exploit a previously unexplored subpocket of the inhibitor binding site. By structural optimization based on the pharmacophore hypothesis, 25 novel compounds were synthesized, among them highly potent CYP11B2 inhibitors (e.g., 17, IC50 = 2.7 nM) with pronounced selectivity toward the most important steroidogenic and hepatic CYP enzymes.

  DOI：

  10.1021/jm800683c
• 作为产物：
  描述：

  2-benzyloxy-3-(4-methoxybenzyl)naphthalene 在 palladium 10% on activated carbon 、 甲酸铵 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以86%的产率得到3-(4-methoxybenzyl)naphthalen-2-ol
  参考文献：
  名称：

  Novel Aldosterone Synthase Inhibitors with Extended Carbocyclic Skeleton by a Combined Ligand-Based and Structure-Based Drug Design Approach

  摘要：

  Pharmacophore modeling of a series of aldosterone synthase (CYP11B2) inhibitors triggered the design of compounds 11 and 12 by extending a previously established naphthalene molecular scaffold (e.g., present in molecules 1 and 2) via introduction of a phenyl or benzyl residue in 3-position. These additional aromatic moieties have been hypothesized to fit into the newly identified hydrophobic pharmacophore feature HY3. Subsequent docking studies in our refined CYP11B2 protein model have been performed prior to synthesis to estimate the inhibitory properties of the proposed molecules. While phenyl-substituted compound 11 (IC50 > 500 nM) did not dock under the given pharmacophore constraint (i.e., the Fe(heme)-N(ligand) interaction), benzyl-substituted compound 12 (IC50 = 154 nM) was found to exploit a previously unexplored subpocket of the inhibitor binding site. By structural optimization based on the pharmacophore hypothesis, 25 novel compounds were synthesized, among them highly potent CYP11B2 inhibitors (e.g., 17, IC50 = 2.7 nM) with pronounced selectivity toward the most important steroidogenic and hepatic CYP enzymes.

  DOI：

  10.1021/jm800683c

文献信息

• Transition-Metal-Free Alkylative Aromatization of Tetralone Using Alcohol/Amino Alcohol towards the Synthesis of Bioactive Naphthol and Benzo[<i>e</i>/<i>g</i>]indole Derivatives
  作者：Akash S. Ubale、Gokul S. Londhe、Moseen A. Shaikh、Boopathy Gnanaprakasam

  DOI：10.1021/acs.joc.2c00779

  日期：2022.6.17

  Herein, we report alkylative aromatization of tetralone for the synthesis of bioactive naphthols and benzo[e/g]indole derivatives using alcohols in the presence of NaOH via an aerobic oxidative cross-coupling protocol. This is a general and transition-metal-free method, which uses an inexpensive base, avoids inert conditions, and furnishes water and hydrogen peroxide as the byproducts. Moreover, this

  在此，我们报告了四氢萘酮的烷基芳构化，用于在NaOH 存在下通过需氧氧化交叉偶联方案使用醇合成生物活性萘酚和苯并[ e / g ]吲哚衍生物。这是一种通用且不含过渡金属的方法，它使用廉价的碱，避免惰性条件，并提供水和过氧化氢作为副产品。此外，该方法具有广泛的底物范围，并获得了独有的区域选择性。