N-(2-(3,4-dimethoxyphenyl)ethyl)-2-(4-hydroxyphenyl)acetamide | 10214-84-3

• 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-(4-hydroxyphenyl)acetamide
• 英文别名: N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-hydroxyphenyl)acetamide；N-(3,4-dimethoxyphenethyl)-2-(4-hydroxyphenyl)acetamide；N-β-(3,4-Dimethoxyphenaethyl)-4-hydroxyphenylacetamid；N-(3.4-Dimethoxyphenethyl)-2-(p-hydroxyphenyl)-acetamid；N-[2-(3,4-Dimethoxyphenyl)ethyl]-2-(4-hydroxyphenyl)ethanimidic acid
• CAS: 10214-84-3
• 化学式: C₁₈H₂₁NO₄
• 分子量: 315.369
• InChiKey: AFXJJRRNCJTPND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-(3,4-dimethoxyphenyl)ethyl)-2-(4-hydroxyphenyl)acetamide 在 碘苯二乙酸 、 磷酸 、 三氟化硼乙醚 、 双(三甲基硅烷基)氨基钾 、 三乙胺 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 5.83h， 生成 11,12-dimethoxy-8,9-dihydro-1H-indolo[7a,1-a]isoquinoline-2,6-dione
  参考文献：
  名称：

  赤藓生物碱异烟酰胺的合成

  摘要：

  从廉价的苯酚和胺衍生物开始，即可实现简明合成的异黄ram烷（类紫杉碱家族的一种生物碱）。该合成基于由高价碘试剂介导的氧化苯酚脱芳香化作用，并且包括通往关键吲哚满酮部分的新途径。

  DOI：

  10.1021/jo501583c
• 作为产物：
  描述：

  对羟基苯乙酸 、 3,4-二甲氧基苯乙胺 在 硼酸 作用下， 以 甲苯 为溶剂， 生成 N-(2-(3,4-dimethoxyphenyl)ethyl)-2-(4-hydroxyphenyl)acetamide
  参考文献：
  名称：

  粉防己碱的简化衍生物作为有效且特异性的 P-gp 抑制剂，可逆转癌症化疗中的多药耐药性

  摘要：

  靶向抑制药物外排转运蛋白 P-糖蛋白 (P-gp) 是逆转癌症化疗中多药耐药性的重要策略。本研究基于分子动力学模拟和片段生长对天然粉防己碱进行了合理的结构简化，得到了一种易于制备、新颖且简化的化合物OY-101，具有高逆转活性和低细胞毒性。通过逆转活性测定、流式细胞术、平板克隆形成测定和药物协同分析证实其与长春新碱（VCR）对耐药细胞Eca109/VCR具有优异的协同抗癌作用（IC 50 = 9.9 nM，RF = 690） 。进一步的机制研究证实OY-101是一种特异性、高效的P-gp抑制剂。重要的是，OY-101增加了体内VCR 致敏性，但没有明显的毒性。总体而言，我们的研究结果可能为设计新型特异性 P-gp 抑制剂作为抗肿瘤化疗增敏剂提供替代策略。

  DOI：

  10.1021/acs.jmedchem.2c02061

文献信息

• Synthesis and Biological Evaluation of Novel Gigantol Derivatives as Potential Agents in Prevention of Diabetic Cataract
  作者：Jie Wu、Chuanjun Lu、Xue Li、Hua Fang、Wencheng Wan、Qiaohong Yang、Xiaosheng Sun、Meiling Wang、Xiaohong Hu、C.-Y. Oliver Chen、Xiaoyong Wei

  DOI：10.1371/journal.pone.0141092

  日期：——

  As a continuation of our efforts directed towards the development of natural anti-diabetic cataract agents, gigantol was isolated from Herba dendrobii and was found to inhibit both aldose reductase (AR) and inducible nitric oxide synthase (iNOS) activity, which play a significant role in the development and progression of diabetic cataracts. To improve its bioefficacy and facilitate use as a therapeutic agent, gigantol (compound 14f) and a series of novel analogs were designed and synthesized. Analogs were formulated to have different substituents on the phenyl ring (compounds 4, 5, 8, 14a-e), substitute the phenyl ring with a larger steric hindrance ring (compounds 10, 17c) or modify the carbon chain (compounds 17a, 17b, 21, 23, 25). All of the analogs were tested for their effect on AR and iNOS activities and on D-galactose-induced apoptosis in cultured human lens epithelial cells. Compounds 5, 10, 14a, 14b, 14d, 14e, 14f, 17b, 17c, 23, and 25 inhibited AR activity, with IC50 values ranging from 5.02 to 288.8 μM. Compounds 5, 10, 14b, and 14f inhibited iNOS activity with IC50 ranging from 432.6 to 1188.7 μM. Compounds 5, 8, 10, 14b, 14f, and 17c protected the cells from D-galactose induced apoptosis with viability ranging from 55.2 to 76.26%. Of gigantol and its analogs, compound 10 showed the greatest bioefficacy and is warranted to be developed as a therapeutic agent for diabetic cataracts.

  作为我们致力于开发天然抗糖尿病性白内障药物的延续，从石斛中分离出巨花素，并发现它能抑制醛糖还原酶（AR）和诱导型一氧化氮合酶（iNOS）的活性，这两种酶在糖尿病性白内障的发展和进展中起着重要作用。为了提高其生物效力和便于作为治疗剂使用，设计并合成了巨花素（化合物14f）及一系列新衍生物。这些衍生物在苯环上有不同的取代基（化合物4、5、8、14a-e），用具有更大立体障碍的环替代苯环（化合物10、17c），或修改碳链（化合物17a、17b、21、23、25）。所有衍生物在体外对AR和iNOS的活性以及在D-半乳糖诱导的人晶状体上皮细胞凋亡中的作用进行了测试。化合物5、10、14a、14b、14d、14e、14f、17b、17c、23和25抑制了AR的活性，IC50值范围为5.02至288.8 μM。化合物5、10、14b和14f抑制了iNOS的活性，IC50范围为432.6至1188.7 μM。化合物5、8、10、14b、14f和17c保护细胞免受D-半乳糖诱导的凋亡，存活率范围为55.2至76.26%。在巨花素及其衍生物中，化合物10显示出最大的生物效力，值得开发为糖尿病性白内障的治疗剂。
• Method and health food for preventing and/or alleviating psychiatric disorder, and/or for effectuating sedation
  申请人：Tanahashi Takao

  公开号：US20060030586A1

  公开（公告）日：2006-02-09

  A method for preventing and/or alleviating a psychiatric disorder, and/or effectuating sedation, comprising administering a benzylisoquinoline derivative represented by General Formula (I): wherein R 1 , R 2 , R 3 and X each represent a particular group; a method for preventing and/or alleviating a particular symptom, comprising administering a bisbenzylisoquinoline derivative represented by General Formula (II): wherein R 7 , R 8 , R 9 , R 10 and R 11 each represent a particular group, and a health food containing said derivative represented by General Formula (I) or (II).

  一种预防和/或缓解精神障碍，和/或实现镇静的方法，包括给予由通用式(I)表示的苯基异喹啉衍生物，其中R1、R2、R3和X分别代表特定基团；一种预防和/或缓解特定症状的方法，包括给予由通用式(II)表示的双苯基异喹啉衍生物，其中R7、R8、R9、R10和R11各自代表特定基团，以及含有所述通用式(I)或(II)所代表的衍生物的保健食品。
• Total Synthesis of (<i>S</i>,<i>S</i>)-Tetramethylmagnolamine via Aerobic Desymmetrization
  作者：Zheng Huang、Xiang Ji、Jean-Philip Lumb

  DOI：10.1021/acs.orglett.9b03559

  日期：2019.11.15

  We describe a concise synthesis of the pseudodimeric tetrahydroisoqunoline alkaloid (S,S)-tetramethylmagnolamine by a catalytic aerobic desymmetrization of phenols. Desymmetrization reactions increase molecular complexity with high levels of efficiency, but those that do so by aerobic oxidation are uncommon. Our conditions employ molecular oxygen as an oxygen atom transfer agent and a formal acceptor

  我们描述了通过苯酚的催化好氧脱对称化的伪二聚体四氢异喹啉生物碱（S，S）-四甲基木酚胺的简洁合成。脱对称反应以高水平的效率增加了分子的复杂性，但是通过有氧氧化进行脱对称反应的情况并不常见。我们的条件使用分子氧作为氧原子转移剂和氢的形式受体，从而实现了两个机械上截然不同的芳族CH氧化反应，并具有很高的选择性。
• Total Synthesis of New 8-(Arylmethyl)berbines
  作者：Maria Valpuesta、Manuela Ariza、Amelia Diaz、Gregorio Torres、Rafael Suau

  DOI：10.1002/ejoc.200901081

  日期：2010.2

  The total synthesis of the natural compound (8S * ,14S * )-8-(4'-hydroxybenzyl)-2,3-dimethoxyberbin-10-ol and its C-8 epimer has been conveniently developed by making use of the diastereoselective Stevens rearrangement of the corresponding N-(arylmethyl)berbinium salts as the key step.

  天然化合物(8S * ,14S * )-8-(4'-羟基苄基)-2,3-二甲氧基berbin-10-ol及其C-8差向异构体的全合成已利用非对映选择性Stevens方便地开发相应的 N-（芳甲基）铽盐的重排是关键步骤。
• Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor
  作者：David A. Perrey、Nadezhda A. German、Ann M. Decker、David Thorn、Jun-Xu Li、Brian P. Gilmour、Brian F. Thomas、Danni L. Harris、Scott P. Runyon、Yanan Zhang

  DOI：10.1021/cn500330v

  日期：2015.4.15

  Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (K-e) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats.