2-methoxy-4-(2-phenylethoxy)benzaldehyde | 149428-72-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-methoxy-4-(2-phenylethoxy)benzaldehyde
• CAS: 149428-72-8
• 化学式: C₁₆H₁₆O₃
• 分子量: 256.301
• InChiKey: QLABYIKJKVBJRA-UHFFFAOYSA-N

物化性质

• 沸点：
  423.0±35.0 °C(Predicted)
• 密度：
  1.132±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methoxy-4-(2-phenylethoxy)benzaldehyde 在 lithium aluminium tetrahydride 、 ammonium acetate 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 生成 2-(2-methoxy-4-(2-phenylethoxy)phenyl)-1-aminoethane
  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-羟基-2-甲氧基苯甲醛 、 乙基溴苯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 2-methoxy-4-(2-phenylethoxy)benzaldehyde
  参考文献：
  名称：

  设计，合成，结构活性关系和作为潜在抗精神病药的新型芳基烷氧基苯基烷基胺西格玛配体的生物学特性。

  摘要：

  sigma受体拮抗剂可能是有效的抗精神病药物，不会引起因摄入氟哌啶醇等经典药物而引起的运动副作用。我们获得的证据表明，1-（2-二丙基氨基乙基）-4-甲氧基-6H-二苯并[b，d]吡喃盐酸盐2a对sigma受体的选择性亲和力高于多巴胺D2受体。设计该化合物可消除阿扑吗啡1的两个键，从而为氮原子产生结构柔性，并通过-CH2O-键桥接两个苯环，以维持平面结构。根据证据，设计了N，N-二丙基-2-（4-甲氧基-3-苄氧基苯基）乙胺盐酸盐10b。由于化合物10b消除了6H-二苯并[b，d]吡喃衍生物2a的联苯键，因此与化合物2a相比，它可能从阿扑吗啡1的刚性结构中释放出来。化合物10b的化学修饰导致人们发现，N，N-二丙基-2- [4-甲氧基-3-（2-苯基乙氧基）苯基]乙胺盐酸盐10g（NE-100）是芳基烷氧基苯基烷基胺衍生物3中最好的化合物，口服该药物对sigma受体具有很高的选择性亲和力，

  DOI：

  10.1021/jm980212v

文献信息

• Design, Synthesis, Structure−Activity Relationships, and Biological Characterization of Novel Arylalkoxyphenylalkylamine σ Ligands as Potential Antipsychotic Drugs
  作者：Atsuro Nakazato、Kohmei Ohta、Yoshinori Sekiguchi、Shigeru Okuyama、Shigeyuki Chaki、Yutaka Kawashima、Katsuo Hatayama

  DOI：10.1021/jm980212v

  日期：1999.3.1

  sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2 receptor. This compound was designed to eliminate two bonds of apomorphine 1 to produce

  sigma受体拮抗剂可能是有效的抗精神病药物，不会引起因摄入氟哌啶醇等经典药物而引起的运动副作用。我们获得的证据表明，1-（2-二丙基氨基乙基）-4-甲氧基-6H-二苯并[b，d]吡喃盐酸盐2a对sigma受体的选择性亲和力高于多巴胺D2受体。设计该化合物可消除阿扑吗啡1的两个键，从而为氮原子产生结构柔性，并通过-CH2O-键桥接两个苯环，以维持平面结构。根据证据，设计了N，N-二丙基-2-（4-甲氧基-3-苄氧基苯基）乙胺盐酸盐10b。由于化合物10b消除了6H-二苯并[b，d]吡喃衍生物2a的联苯键，因此与化合物2a相比，它可能从阿扑吗啡1的刚性结构中释放出来。化合物10b的化学修饰导致人们发现，N，N-二丙基-2- [4-甲氧基-3-（2-苯基乙氧基）苯基]乙胺盐酸盐10g（NE-100）是芳基烷氧基苯基烷基胺衍生物3中最好的化合物，口服该药物对sigma受体具有很高的选择性亲和力，
• Chitosan-silica Sulfate Nano Hybrid: An Efficient Biopolymer Based-heterogeneous Nano Catalyst for Solvent-free Synthesis of 3,4-Dihydropyrimidine-2(1H)-one/thiones
  作者：Somayeh Behrouz、Masoome Nazar Abi、Mohammad Amin Piltan

  DOI：10.17344/acsi.2020.6343

  日期：——

  A green and highly efficient approach for the synthesis of 3,4-dihydropyrimidine-2(1H)-one/thione derivatives is described. In this approach, the three-component Biginelli reaction between (thio)urea, methyl acetoacetate and aldehydes under solvent-free condition in the presence of chitosan-silica sulfate nano hybrid (CSSNH) as a green and heterogeneous nano catalyst affords the corresponding products in good to excellent yields and in short reaction times. CSSNH is a cheap, eco-friendly, and non-toxic nano catalyst that could be easily prepared, handled, and reused for many reaction runs without significant loss of its activity.

  描述了一种绿色高效的方法，用于合成3,4-二氢嘧啶-2(1H)-酮/硫代嘧啶衍生物。在这种方法中，在无溶剂条件下，在壳聚糖-硅酸盐纳米杂化物(CSSNH)存在下，(硫)脲、乙酰乙酸甲酯和醛之间进行三组分Biginelli反应，产生相应的产物，收率良好至优良，并在短时间内完成反应。CSSNH是一种便宜、环保、无毒的纳米催化剂，可以轻松制备、处理和重复使用多次而不显著降低其活性。
• ALKOXYPHENYLALKYLAMINE DERIVATIVE
  申请人：TAISHO PHARMACEUTICAL CO. LTD

  公开号：EP0641766A1

  公开（公告）日：1995-03-08

  An alkoxyphenylalkylamine derivative represented by general formula (I) and a salt thereof, wherein X¹ and X² may be the same or different from each other and each represents hydrogen, halogen, hydroxyl, or C₁ to C₅ alkoxy which may be substituted by phenyl; R¹ and R² may be the same or different from each other and each represents hydrogen or C₁ to C₇ alkyl which may be terminated with hydroxyl, carboxyl or alkoxycarbonyl, or alternatively R¹ and R² are combined with the adjacent nitrogen atoms to represent optionally substituted pyrrolidine, piperidino, piperazino, etc.; A represents phenyl which may be substituted by one to three arbitrary substituents selected among halogen, hydroxyl and C₁ to C₅ alkoxy, or similarly substituted thienyl; m represents an integer of 2 to 5; and n represents an integer of 1 to 7. The above compounds are useful in treating schizophrenia without causing extrapyramidal disorder and in treating problematic behaviours accompanying cerebrovascular disorder or senile dementia.

  通式(I)代表的烷氧基苯烷基胺衍生物及其盐，其中 X¹ 和 X² 可以相同或不同，各自代表氢、卤素、羟基或可被苯基取代的 C₁ 至 C₅ 烷氧基；R¹ 和 R² 可以相同或互不相同，各自代表氢或 C₁ 至 C₇ 烷基，可以用羟基、羧基或烷氧基羰基封端，或者 R¹ 和 R² 与相邻的氮原子结合代表任选取代的吡咯烷、哌啶基、哌嗪基等。A 代表苯基，可被选自卤素、羟基和 C₁ 至 C₅ 烷氧基或类似取代的噻吩基中的一至三个任意取代基取代；m 代表 2 至 5 的整数；n 代表 1 至 7 的整数。上述化合物可用于治疗精神分裂症，但不会引起锥体外系障碍，也可用于治疗伴随脑血管障碍或老年痴呆症的问题行为。
• US5495046A
  申请人：——

  公开号：US5495046A

  公开（公告）日：1996-02-27
• 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.