N-[2-(3,4-dimethoxyphenyl)-ethyl]-2-hydroxy-2-(4-methoxyphenyl)ethylamine | 62717-74-2

• 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: N-[2-(3,4-dimethoxyphenyl)-ethyl]-2-hydroxy-2-(4-methoxyphenyl)ethylamine
• 英文别名: N-<2-hydroxy-2-(4-methoxyphenyl)ethyl>-2-(3,4-dimethoxyphenyl)ethylamine；N-[2-(3,4-dimethoxyphenyl)ethyl]-2-hydroxy-2-(4-methoxyphenyl)ethylamine；N-<2-(3,4-Dimethoxyphenyl)-ethyl>-2-hydroxy-2-(4-methoxyphenyl)-ethylamin；2-[2-(3,4-dimethoxyphenyl)ethylamino]-1-(4-methoxyphenyl)ethanol
• CAS: 62717-74-2
• 化学式: C₁₉H₂₅NO₄
• 分子量: 331.412
• InChiKey: ARQYVLCQEUBWQV-UHFFFAOYSA-N

物化性质

• 熔点：
  92 °C
• 沸点：
  501.3±50.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  60
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[2-(3,4-dimethoxyphenyl)-ethyl]-2-hydroxy-2-(4-methoxyphenyl)ethylamine 在 硫酸 、 三氟乙酸 作用下， 反应 3.5h， 以60%的产率得到7,8-dimethoxy-5-(4-methoxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine
  参考文献：
  名称：

  多巴胺激动剂1-芳基-2,3,4,5-四氢-1H-3-苯并ze庚因-7,8-二醇的合成及其肾脏血管舒张活性：非诺多old的卤素和甲基类似物。

  摘要：

  发现某些6-卤代-1-苯基-2,3,4,5-四氢-1H-3-苯并ze庚因是有效的D-1多巴胺激动剂。1-（4-羟苯基）类似物不具有中枢神经系统活性，因为它们的高极性抑制了其进入大脑。但是，这些化合物是有效的肾血管扩张药。非氯多巴，6-氯类似物，是该系列中特别重要的成员，其合成，药理和临床特性已得到广泛研究。6-甲基和6-碘同系物是有效的肾血管扩张剂，但通过刺激大鼠尾状腺苷酸环化酶测定，非有效的部分D-1激动剂。可能的合理化建议这些活动具有不同的受体储备。9位取代的苯并庚因多巴胺激动剂不活跃或效力低下，

  DOI：

  10.1021/jm00161a029
• 作为产物：
  描述：

  3,4-二甲氧基苯乙酸 在 sodium hydroxide 、 氯化亚砜 、 dimethylamine borane 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 N-[2-(3,4-dimethoxyphenyl)-ethyl]-2-hydroxy-2-(4-methoxyphenyl)ethylamine
  参考文献：
  名称：

  Dopamine agonists related to 3-allyl-6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-diol, 6-position modifications

  摘要：

  The N-allyl derivative (SK&F 85174) of 6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-diol (SK&F 82526) retains the DA-1 agonist potency of the latter compound but unlike the parent also shows substantial DA-2 agonist activity. In a previous study of N-substituted benzazepines these combined agonist effects were shown to be uniquely associated with the N-allyl group. A continuation of this research has examined dependency of combined DA-2/DA-1 agonist activities on 6-position modification with the specific objective of developing an agonist with maximum effectiveness and potency at the DA-2 receptor subtype. DA-2 agonist activity was measured in a rabbit ear artery assay, and DA-1 agonist activity was determined in an adenylate cyclase assay. Replacing chloro with bromo retains the activity pattern and the potency of the chloro compound; replacement with a hydrogen causes a decrease of both DA-1 and DA-2 receptor activating potency. Introduction of a 6-methyl group causes loss of DA-2 agonist activity and reduction in DA-1 agonist potency. Substitution with a 6-fluoro provides the best balance of DA-2 and DA-1 agonist activities; this compound was moderately potent in both assays.

  DOI：

  10.1021/jm00384a006

文献信息

• 2,3,4,5-Tetrahydro-1H-3-benzazepine-7,8-diones
  申请人：SmithKline Corporation

  公开号：US04108989A1

  公开（公告）日：1978-08-22

  Novel benzazepine derivatives having central and peripheral dopaminergic activity useful in treating Parkinson's and cardiovascular diseases. The compounds have additional use as intermediates for the synthesis of other benzazepines with similar useful properties. The 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-dione derivatives are particularly useful.

  新型苯并哌啶衍生物具有中枢和外周多巴胺活性，可用于治疗帕金森病和心血管疾病。这些化合物还可用作合成具有类似有用性质的其他苯并哌啶的中间体。其中1-苯基-2,3,4,5-四氢-1H-3-苯并哌啶-7,8-二酮衍生物特别有用。
• Primary Alkylboronic Acids as Highly Active Catalysts for the Dehydrative Amide Condensation of α-Hydroxycarboxylic Acids
  作者：Risa Yamashita、Akira Sakakura、Kazuaki Ishihara

  DOI：10.1021/ol401537f

  日期：2013.7.19

  Primary alkylboronic acids such as methylboronic acid and butylboronic acid are highly active catalysts for the dehydrative amide condensation of α-hydroxycarboxylic acids. The catalytic activities of these primary alkylboronic acids are much higher than those of the previously reported arylboronic acids. The present method was easily applied to a large-scale synthesis, and 14 g of an amide was obtained

  伯烷基硼酸，例如甲基硼酸和丁基硼酸，是用于α-羟基羧酸脱水酰胺缩合的高活性催化剂。这些伯烷基硼酸的催化活性比以前报道的芳基硼酸的催化活性高得多。本方法容易用于大规模合成，并且在单个反应中获得14g酰胺。
• Non-enzymatic oxidation of the new cardiotonic agent denopamine and its derivatives: Comparison with enzymatic oxidation.
  作者：TOSHIKAZU SUZUKI、YOSHIMASA HASHIMURA、SHIGEYUKI TAKEYAMA

  DOI：10.1248/cpb.33.3859

  日期：——

  Chemical oxidation of the positive inotropic agent denopamine, (-)-(R)-1-(p-hydroxyphenyl)-2-[(3, 4-dimethoxyphenethyl) amino] ethanol, and its derivatives by Udenfriend's model system for enzymatic oxidation was studied. The oxidation products were separated and identified by gas chromatography-mass spectrometry and high-performance liquid chromatography. All the metabolites of denopamine produced by enzymatic oxidation were also formed in Udenfriend's system. However, compared to enzymatic oxidation, the chemical oxidation was less selective as to the position of demethylation : i.e., although enzymatic 4'-O-demethylation took place overwhelmingly in preference to 3'-O-demethylation, comparable amounts of the two demethylated isomers were produced in Udenfriend's system. It was also found that the chemical oxidation was more powerful than the enzymatic oxidation because hydroxylation at the ortho or para position to the methoxy group took place in all the substrates tested, while such metabolites have not been detected in biological systems. As in the enzymatic system, tetrahydroisoquinoline-type compounds were formed from substrates in which the hydroxy group was attached at the meta position of the benzene ring. This is presumably a result of Pictet-Spengler-type condensation with formaldehyde generated in the reaction mixture.

  研究了正性肌力药地诺帕明、(-)-(R)-1-(对羟基苯基)-2-[(3, 4-二甲氧基苯乙基)氨基]乙醇及其衍生物在 Udenfriend 酶促氧化模型系统中的化学氧化作用。氧化产物通过气相色谱-质谱法和高效液相色谱法进行分离和鉴定。酶法氧化产生的所有地诺帕明代谢物在 Udenfriend 系统中也有形成。不过，与酶促氧化法相比，化学氧化法对去甲基化位置的选择性较低：也就是说，虽然酶促 4'-O- 去甲基化比 3'-O- 去甲基化更占优势，但在 Udenfriend 体系中产生的两种去甲基化异构体的数量相当。研究还发现，化学氧化作用比酶法氧化作用更强，因为在所有测试的底物中，甲氧基的正位或对位都发生了羟基化反应，而在生物系统中还没有检测到这种代谢物。在酶系统中，羟基连接在苯环元位置的底物会形成四氢异喹啉类化合物。这可能是与反应混合物中产生的甲醛进行 Pictet-Spengler 型缩合的结果。
• Pharmaceutical compositions and methods involving benzazepine derivatives
  申请人：SmithKline Corporation

  公开号：US04011319A1

  公开（公告）日：1977-03-08

  Pharmaceutical compositions and a method of stimulating peripheral dopamine receptors by administering internally a nontoxic effective quantity of a benzazepine derivative to an animal. Renal vasodilator and diuretic methods are also disclosed.

  一种药物组合物和一种方法，通过向动物内部给予一种苯并噻吩衍生物的无毒有效剂量来刺激外周多巴胺受体。还揭示了肾脏扩血管和利尿的方法。
• Separation of potent central and renal dopamine agonist activity in substituted 6-chloro-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepines
  作者：Joseph Weinstock、James W. Wilson、David L. Ladd、Charles K. Brush、Francis R. Pfeiffer、George Y. Kuo、Kenneth G. Holden、Nelson C. F. Yim、Richard A. Hahn

  DOI：10.1021/jm00183a001

  日期：1980.9