4-bromo-2,5-dimethoxybenzaldehyde | 370884-62-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-bromo-2,5-dimethoxybenzaldehyde
• 英文别名: 4-bromo-5-hydroxy-2-methoxybenzaldehyde
• CAS: 370884-62-1
• 化学式: C₈H₇BrO₃
• 分子量: 231.046
• InChiKey: NIXBOCFPRJNONN-UHFFFAOYSA-N

物化性质

• 沸点：
  320.3±42.0 °C(Predicted)
• 密度：
  1.653±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-bromo-2,5-dimethoxybenzaldehyde 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 三氯化铝 、 Adogen-464 、 ammonium acetate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 2-[4-Bromo-2-methoxy-5-(2-phenylethoxy)phenyl]ethanamine
  参考文献：
  名称：

  1-[2-Methoxy-5-(3-phenylpropyl)]-2-aminopropane Unexpectedly Shows 5-HT_2A Serotonin Receptor Affinity and Antagonist Character

  摘要：

  Certain phenylethylamines, such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; 1a), are high-affinity 5-HT2 agonists. Previous structure-affinity studies have concluded that both the 2,5-dimethoxy substitution pattern and the nature of substituents at the 4-position are important determinants of high affinity. We recently demonstrated that replacement of the bromo group of DOB with a 3-(phenyl)propyl substituent results in retention of affinity and that, counter to established structure-affinity relationships, the 2,5-dimethoxy substitution pattern is no longer a requirement for the binding. The present investigation extends these findings by examining a series of analogues, 3, lacking a 5-methoxy group. It was additionally found that shifting the phenylalkyl substituent from the 4- to the 5-position (e.g., 4i) also results in retention of affinity. For example, 1-(2-methoxy-5-(3-phenylpropyl)-2-aminopropane (6; the alpha -methyl derivative of 4i) binds at 5-HT2A receptors with high affinity (K-i = 13 nM) and possesses 5-HT2A antagonist character. Thus, not only is the 2,5-dimethoxy substitution pattern not a requirement for the binding of certain phenylethylamines at 5-HT2A receptors, the presence of a 4-position substituent (previously thought to serve as a modulator of affinity of DOB-like agents) is also not required. Striking differences in the 5-HT2A binding requirements of the present compounds as compared to DOB-like agents suggest multiple substituent-dependent modes of binding.

  DOI：

  10.1021/jm0100739
• 作为产物：
  描述：

  4-溴-2,5-二甲氧基苯甲醛 在 硫酸 作用下， 反应 48.0h， 以55%的产率得到4-bromo-2,5-dimethoxybenzaldehyde
  参考文献：
  名称：

  1-[2-Methoxy-5-(3-phenylpropyl)]-2-aminopropane Unexpectedly Shows 5-HT_2A Serotonin Receptor Affinity and Antagonist Character

  摘要：

  Certain phenylethylamines, such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; 1a), are high-affinity 5-HT2 agonists. Previous structure-affinity studies have concluded that both the 2,5-dimethoxy substitution pattern and the nature of substituents at the 4-position are important determinants of high affinity. We recently demonstrated that replacement of the bromo group of DOB with a 3-(phenyl)propyl substituent results in retention of affinity and that, counter to established structure-affinity relationships, the 2,5-dimethoxy substitution pattern is no longer a requirement for the binding. The present investigation extends these findings by examining a series of analogues, 3, lacking a 5-methoxy group. It was additionally found that shifting the phenylalkyl substituent from the 4- to the 5-position (e.g., 4i) also results in retention of affinity. For example, 1-(2-methoxy-5-(3-phenylpropyl)-2-aminopropane (6; the alpha -methyl derivative of 4i) binds at 5-HT2A receptors with high affinity (K-i = 13 nM) and possesses 5-HT2A antagonist character. Thus, not only is the 2,5-dimethoxy substitution pattern not a requirement for the binding of certain phenylethylamines at 5-HT2A receptors, the presence of a 4-position substituent (previously thought to serve as a modulator of affinity of DOB-like agents) is also not required. Striking differences in the 5-HT2A binding requirements of the present compounds as compared to DOB-like agents suggest multiple substituent-dependent modes of binding.

  DOI：

  10.1021/jm0100739

文献信息

• [EN] SUBSTITUTED CHROMEN-4-ONE FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION<br/>[FR] CHROMÈNE-4-ONE SUBSTITUÉE POUR LE TRAITEMENT ET LA PROPHYLAXIE D'UNE INFECTION PAR LE VIRUS DE L'HÉPATITE B
  申请人：HOFFMANN LA ROCHE

  公开号：WO2020148354A1

  公开（公告）日：2020-07-23

  The present invention provides novel compounds having the general formula: (I) wherein R1 to R10, Gi, G2 and m are as described herein, compositions including the impounds and methods of using the compounds for the treatment of hepatitis B.

  本发明提供具有一般式(I)的新化合物，其中R1至R10、Gi、G2和m如本文所述，包括这些化合物的组合物以及使用这些化合物用于治疗乙型肝炎的方法。
• N-Heterocyclic Carbene-Catalyzed Highly Enantioselective Macrolactonization to Access Planar-Chiral Macrocycles
  作者：Jiaming Wang、Meng Wang、Yilu Wen、Peng Teng、Chenyang Li、Changgui Zhao

  DOI：10.1021/acs.orglett.3c04200

  日期：2024.2.9

  An N-heterocyclic carbene (NHC)-catalyzed atroposelective macrolactonization has been disclosed. This approach affords planar-chiral macrocycles in high yields with excellent enantioselectivities over a broad substrate scope. Controlled experiments suggest that the enantioselectivity might arise from the cation–n interaction between the acyl azolium and the electron-rich moiety in the substrate. This

  已经公开了N-杂环卡宾(NHC)催化的阻转选择性大内酯化。这种方法能够以高产率提供平面手性大环化合物，并在广泛的底物范围内具有优异的对映选择性。对照实验表明，对映选择性可能源于酰基唑鎓与底物中富电子部分之间的阳离子-n相互作用。该机制得到了密度泛函理论计算的支持，这也表明了稳定过渡态中重要的 π-π 相互作用。
• 5-HT_2A/5-HT_2C Receptor Pharmacology and Intrinsic Clearance of <i>N</i>-Benzylphenethylamines Modified at the Primary Site of Metabolism
  作者：Sebastian Leth-Petersen、Ida N. Petersen、Anders A. Jensen、Christoffer Bundgaard、Mathias Bæk、Jan Kehler、Jesper L. Kristensen

  DOI：10.1021/acschemneuro.6b00265

  日期：2016.11.16

  The toxic hallucinogen 25B-NBOMe is very rapidly degraded by human liver microsomes and has low oral bioavailability. Herein we report on the synthesis, microsomal stability, and S-HT2A/5-HT2C receptor profile of novel analogues of 25B-NBOMe modified at the primary site of metabolism. Although microsomal stability could be increased while maintaining potent 5-HT2 receptor agonist properties, all analogues had an intrinsic clearance above 1.3 L/kg/h predictive of high first-pass metabolism.
• SUBSTITUTED CHROMEN-4-ONE FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3911413A1

  公开（公告）日：2021-11-24
• 1-[2-Methoxy-5-(3-phenylpropyl)]-2-aminopropane Unexpectedly Shows 5-HT_2A Serotonin Receptor Affinity and Antagonist Character
  作者：Jagadeesh B. Rangisetty、Małgorzata Dukat、Cynthia S. Dowd、Katharine Herrick-Davis、Ann DuPre、Sami Gadepalli、Milt Teitler、Curtis R. Kelley、Najam A. Sharif、Richard A. Glennon

  DOI：10.1021/jm0100739

  日期：2001.9.1

  Certain phenylethylamines, such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; 1a), are high-affinity 5-HT2 agonists. Previous structure-affinity studies have concluded that both the 2,5-dimethoxy substitution pattern and the nature of substituents at the 4-position are important determinants of high affinity. We recently demonstrated that replacement of the bromo group of DOB with a 3-(phenyl)propyl substituent results in retention of affinity and that, counter to established structure-affinity relationships, the 2,5-dimethoxy substitution pattern is no longer a requirement for the binding. The present investigation extends these findings by examining a series of analogues, 3, lacking a 5-methoxy group. It was additionally found that shifting the phenylalkyl substituent from the 4- to the 5-position (e.g., 4i) also results in retention of affinity. For example, 1-(2-methoxy-5-(3-phenylpropyl)-2-aminopropane (6; the alpha -methyl derivative of 4i) binds at 5-HT2A receptors with high affinity (K-i = 13 nM) and possesses 5-HT2A antagonist character. Thus, not only is the 2,5-dimethoxy substitution pattern not a requirement for the binding of certain phenylethylamines at 5-HT2A receptors, the presence of a 4-position substituent (previously thought to serve as a modulator of affinity of DOB-like agents) is also not required. Striking differences in the 5-HT2A binding requirements of the present compounds as compared to DOB-like agents suggest multiple substituent-dependent modes of binding.