1,2,3,4-tetrahydro-6-methoxy-1-phenyl-isoquinoline | 25263-48-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 1,2,3,4-tetrahydro-6-methoxy-1-phenyl-isoquinoline
• 英文别名: 6-methoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline；6-methoxy-1-phenyl-1,2,3,4-tetrahydro-isoquinoline；1,2,3,4-Tetrahydro-6-methoxy-1-phenylisochinolin
• CAS: 25263-48-3
• 化学式: C₁₆H₁₇NO
• mdl: MFCD09886924
• 分子量: 239.317
• InChiKey: XGLBDOMSNOULHH-UHFFFAOYSA-N

物化性质

• 沸点：
  382.3±42.0 °C(Predicted)
• 密度：
  1.085±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,2,3,4-tetrahydro-6-methoxy-1-phenyl-isoquinoline 在 甲酸 、 氢溴酸 作用下， 反应 16.0h， 生成 N-methyl-6-hydroxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Synthesis and Molecular Modeling of 1-Phenyl-1,2,3,4-tetrahydroisoquinolines and Related 5,6,8,9-Tetrahydro-13bH-dibenzo[a,h]quinolizines as D1 Dopamine Antagonists

  摘要：

  New 1-phenyl-1,2,3,4-tetrahydroisoquinolines and related 5,6,8,9-tetrahydro-13bH-dibenzo[a,h]-quinolizines were prepared as ring-contracted analogs of the prototypical 1-phenyl-2,3,4,5-tetrahydrobenzazepines (e.g., SCH23390) as a continuation of our studies to characterize the antagonist binding pharmacophore of the D-1 dopamine receptor. Receptor affinity was assessed by competition for [H-3]SCH23390 binding sites in rat striatal membranes. The 6-bromo-1-phenyltetrahydroisoquinoline analog 2 of SCH23390 1 had D-1 binding affinity similar to that for the previously reported 6-chloro analog 6, whereas the 6,7-dihydroxy analog 5 had significantly lower D-1 affinity. Conversely, neither 6-monohydroxy- (3) nor 7-monohydroxy-1-phenyltetrahydroisoquinolines (4) had significant affinity for the D-1 receptor. These results demonstrate that 6-halo and 7-hydroxy substituents influence D-1 binding affinity of the 1-phenyltetrahydroisoquinolines in a fashion similar to their effects on 1-phenyltetrahydrobenzazepines. azepines. The conformationally constrained 3-chloro-2-hydroxytetrahydrodibenzoquinolizine 9 had much lower affinity relative to the corresponding, and more flexible, 6-chloro-7-hydroxy-1-phenyltetrahydroisoquinoline 6. Similarly, 2,3-dihydroxytetrahydrodibenzoquinolizine 10 had much lower D-1 affinity compared to dihydrexidine 14, a structurally similar hexahydrobenzo[a]phenanthridine that is a high-affinity full D-1 agonist. Together, these data not only confirm the effects of the halo and hydroxy substitutents on the parent nucleus but demonstrate the pharmacophoric importance of both the nitrogen position and the orientation of the accessory phenyl ring in modulating D-1 receptor affinity and function. Molecular modeling studies and conformational analyses were conducted using the data from these new analogs in combination with the data from compounds previously synthesized. The resulting geometries were used to refine a working model of the D-1 antagonist pharmacophore using conventional quantitative structure-activity relationships and three-dimensional QSAR (CoMFA).

  DOI：

  10.1021/jm00051a008
• 作为产物：
  描述：

  N-(3-甲氧基苯乙基)甲酰胺 在 三氟乙酸 、 三氯氧磷 作用下， 生成 1,2,3,4-tetrahydro-6-methoxy-1-phenyl-isoquinoline
  参考文献：
  名称：

  Euerby, Melvin R.; Waigh, Roger D., Journal of Chemical Research, Miniprint, 1987, # 2, p. 501 - 526

  摘要：

  DOI：

文献信息

• [EN] COMPOUNDS AND METHODS<br/>[FR] COMPOSÉS ET MÉTHODES
  申请人：TEMPERO PHARMACEUTICALS INC

  公开号：WO2013019682A1

  公开（公告）日：2013-02-07

  The present invention relates to novel retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORy.

  本发明涉及新型视黄醛酸相关孤儿受体γ（RORγ）调节剂及其在治疗由RORγ介导的疾病中的应用。
• 3D Pharmacophore Models for 1,2,3,4-Tetrahydroisoquinoline Derivatives Acting as Anticonvulsant Agents
  作者：Laura De Luca、Rosaria Gitto、Maria Letizia Barreca、Roberta Caruso、Silvana Quartarone、Rita Citraro、Giovambattista De Sarro、Alba Chimirri

  DOI：10.1002/ardp.200600022

  日期：2006.7

  A 3D pharmacophore model predicting anticonvulsant activity was obtained for a series of 6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline derivatives recently disclosed as a new class of noncompetitive AMPA receptor antagonists. The training set included 17 compounds with varying potency against audiogenic seizures in DBA/2 mice. The best statistical hypothesis, generated with the HypoGen module of Catalyst

  最近披露的一系列 6,7-二甲氧基-1,2,3,4-四氢异喹啉衍生物作为一类新的非竞争性 AMPA 受体拮抗剂，获得了预测抗惊厥活性的 3D 药效团模型。训练集包括 17 种化合物，它们对 DBA/2 小鼠的听觉癫痫发作具有不同的效力。使用 Catalyst 4.9 的 HypoGen 模块生成的最佳统计假设由五个特征组成：两个氢键受体、两个疏水特征和一个疏水芳族区域，提供了一个相关系数为 0.919 的模型。所获得的模型是设计一些含有四氢异喹啉支架的新型抗惊厥药的有效工具。此外，为了解释新设计的 N-取代衍生物的不同程度的功效，
• In Vivo Evaluation of Selective Carbonic Anhydrase Inhibitors as Potential Anticonvulsant Agents
  作者：Elvira Bruno、Maria R. Buemi、Laura De Luca、Stefania Ferro、Anna-Maria Monforte、Claudiu T. Supuran、Daniela Vullo、Giovambattista De Sarro、Emilio Russo、Rosaria Gitto

  DOI：10.1002/cmdc.201500596

  日期：2016.8.19

  excitation, we hypothesized that they could represent the biological target for the development of new anticonvulsant agents. Therefore, for selected isoquinoline sulfonamides, we preliminarily tested their ability to prevent audiogenic seizures in DBA/2 mice. All compounds were evaluated after intraperitoneal administration, and some of them proved to protect the mice against convulsions. Among this series

  癫痫病是一种常见的神经系统疾病，由抑制性和兴奋性神经传递之间的不平衡引起。众所周知，神经元兴奋性与γ-氨基丁酸（GABA）能量去极化有关。HCO 3 -可以通过膜渗透性碳酸酐酶抑制剂抑制依赖的去极化。我们以前鉴定了一些异喹啉磺酰胺作为人类碳酸酐酶II和VII（hCA II和hCA VII）同工型的有效和选择性抑制剂。鉴于hCA II和hCA VII是参与GABA介导的神经元兴奋的特定同工型，我们假设它们可以代表开发新的抗惊厥药的生物学靶标。因此，对于选定的异喹啉磺酰胺，我们初步测试了它们在DBA / 2小鼠中预防音源性癫痫发作的能力。腹膜内给药后对所有化合物进行评估，其中一些化合物被证明可以保护小鼠免于惊厥。在这一系列化合物中，几种衍生物显示出对目标碳酸酐酶（即hCA II和hCA VII）具有联合体内功效和抑制作用。具体而言，最有趣的分子是1-（4-氨基苯基）-6,7-二甲氧基-3,4-
• A Novel Method for Synthesis of Tetrahydro-2H-oxazolo[2,3-a]isoquinolines
  作者：H.E. Dinesha、N.C. Sandhya、K. Mantelingu

  DOI：10.14233/ajchem.2019.21673

  日期：——

  An efficient and direct method for the synthesis of tetrahydro-2H-oxazolo[2,3-a]isoquinolines is reported. This novel method involves ®T3P mediated in situ oxidation of benzyl alcohols to aldehyde followed by acetic acid mediated [3+2] cycloaddition reaction to afford tetrahydro-2H-oxazolo[2,3- a]isoquinolines in one-pot operation with good to excellent yields. Heterocyclic alcohols also underwent the reaction with tetrahydroquinolines at room temperature

  报道了一种高效直接合成四氢-2H-噁二唑[2,3-a]异喹啉的方法。该新方法涉及在原位氧化苄醇为醛的®T3P介导反应，随后进行乙酸介导的[3+2]环加成反应，从而在一锅反应中以良好至优异的产率合成四氢-2H-噁二唑[2,3-a]异喹啉。杂环醇在室温下也能与四氢喹啉发生反应。
• Diastereoselective synthesis of fused oxazolidines and highly substituted 1H-pyrrolo [2,1-c][1,4] oxazines via C–H functionalization
  作者：Chottanahalli. S. Pavan Kumar、Kachigere. B. Harsha、Kempegowda Mantelingu、Kanchugarakoppal. S. Rangappa

  DOI：10.1039/c5ra10030e

  日期：——

  The first one pot protocol for the diastereoselective synthesis of oxazolo[2,3-c]isoquinoline was achieved by a metal-free, benzoic acid catalyzed reaction of 1,2,3,4-tetrahydroisoquinoline or trypoline with aldehydes under mild conditions via C–H, C–O bond functionalization. A new approach for the synthesis of highly substituted 1H-pyrrolo[2,1-c][1,4]oxazine was carried out.

  在温和的条件下，通过C的无金属苯甲酸催化的1,2,3,4-四氢异喹啉或Trypoline与醛的非金属选择性合成恶唑并[2,3- c ]异喹啉的非对映选择性的第一个反应方案-H，C-O键功能化。开展了一种新的合成高度取代的1 H-吡咯并[2,1- c ] [1,4]恶嗪的方法。