6-苯氧基烟酸甲酯 | 595576-44-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 6-苯氧基烟酸甲酯
• 英文名称: 6-phenoxynicotinic acid methyl ester
• 英文别名: Methyl 6-phenoxynicotinate；methyl 6-phenoxypyridine-3-carboxylate
• CAS: 595576-44-6
• 化学式: C₁₃H₁₁NO₃
• 分子量: 229.235
• InChiKey: FDJSCKXMBLOCMJ-UHFFFAOYSA-N

物化性质

• 沸点：
  341.6±27.0 °C(Predicted)
• 密度：
  1.199±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-苯氧基烟酸甲酯 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 反应 12.0h， 生成 N-{(1S)-1-[[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]-methyl]-2-methylpropyl}-5-phenoxypyridine-2-carboxamide
  参考文献：
  名称：

  Discovery of N-{4-[(3-Hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide Analogues as Selective Kappa Opioid Receptor Antagonists

  摘要：

  There is continuing interest in the discovery and development of new kappa opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [S-35]GTP gamma S binding assay showed that neither compound showed the high potency and kappa opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [S-35]GTP gamma S binding stimulated by the selective kappa opioid agonist U69,593. These studies led to N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyll-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good kappa opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [S-35]GTP gamma S binding assay showed that several of the analogues were potent and selective kappa opioid receptor antagonists.

  DOI：

  10.1021/jm400275h
• 作为产物：
  描述：

  6-氯烟酸 在 potassium carbonate 、 caesium carbonate 作用下， 以 甲醇 、 乙醚 、 甲苯 、 乙腈 为溶剂， 反应 0.5h， 生成 6-苯氧基烟酸甲酯
  参考文献：
  名称：

  1-substituted 4-arylpiperazine as kappa opioid receptor antagonists

  摘要：

  提供的化合物由以下公式表示：其中R、Y3、R1、R2、R3、R4、R6、G、R7、E1、E2、A、B、W、X、Y和Z的定义如下。

  公开号：

  US09512105B2

文献信息

• Cycloauration of substituted 2-phenoxypyridine derivatives and X-ray crystal structure of gold, dichloro[2-[[5-[(cyclopentylamino)carbonyl]-2-pyridinyl-κN]oxy]phenyl-κC]-, (SP-4-3)-
  作者：Yongbao Zhu、Beth R. Cameron、Renato T. Skerlj

  DOI：10.1016/s0022-328x(03)00347-4

  日期：2003.7

  2-phenoxypyridines with different substituents at the 5-position of the pyridine ring was carried out in an CH3CN/H2O medium, leading to isolation of cycloaurated compounds AuCl2(L) (HL=substituted 2-phenoxypyridine ligand) with alkyl, substituted alkyl, phenyl, halo, ester and amido groups. The preparation of cycloaurated compounds involves the formation of an intermediate AuCl3(HL) via coordination reaction between

  在CH 3 CN / H 2 O介质中对吡啶环5位上具有不同取代基的2-苯氧基吡啶进行直接环化，从而分离出环化化合物AuCl 2（L）（HL =取代的2-苯氧基吡啶配体）具有烷基，取代的烷基，苯基，卤素，酯基和酰胺基。化合物的制备包括在室温下通过吡啶配体与NaAuCl 4的配位反应形成中间体AuCl 3（HL），然后在高温下在CH 3 CN / H 2中形成Au-C键。哦，中等。庞大的亲脂性基团的存在降低了环化化合物的收率，并有利于反应物种分解成Au（0）。对于在吡啶环中具有强吸电子取代基（硝基或腈）的配体，未观察到配位反应。具有供电子二甲基氨基的配体在室温下被NaAuCl 4氧化。噻吩基或乙酰基的存在允许分离中间体AuCl 3（HL），但对随后的循环auauration有不利影响。甲基取代的2-苯氧基吡啶配体的直接环金原子化的结果表明，在吡啶环中最靠近Au-N（py）键的6位甲基的存在导
• Substituent Effects of 2-Pyridones on Selective O-Arylation with Diaryliodonium Salts: Synthesis of 2-Aryloxypyridines under Transition­-Metal-Free Conditions
  作者：Dong-Liang Mo、Xiao-Hua Li、Ai-Hui Ye、Cui Liang

  DOI：10.1055/s-0036-1591884

  日期：2018.4

  An efficient transition-metal-free strategy to synthesize 2-aryloxypyridine derivatives has been developed by a selective O-arylation of 2-pyridones with diaryliodonium salts. The reaction was compatible with a series of functional groups for 2-pyridones and diaryliodonium salts such as halides, nitro, cyano, and ester groups. The substituents at the C6-position of 2-pyridones favored O-arylation products because of steric hindrance. The reaction was easily performed on a gram-scale and 6-chloro-2-pyridone was a good precursor to access various unsubstituted 2-aryloxypyridines by dehalogenation. A P2Y1 lead compound analogue could be prepared in good yield over two steps.

  开发了一种高效的过渡金属自由策略，通过选择性的氧芳基化2-吡啶酮与二芳基碘盐合成2-芳氧基吡啶衍生物。该反应与一系列功能团对2-吡啶酮和二芳基碘盐兼容，如卤素、硝基、氰基和酯基等。2-吡啶酮的C6位取代基有利于氧芳基化产物的生成，因为存在立体位阻。该反应易于在克级规模上进行，并且6-氯-2-吡啶酮是通过去卤代法获得各种未取代的2-芳氧基吡啶的良好前体。通过两步反应可以以较高产率制备P2Y1前体类似物。
• Design, Synthesis, and Structure–Activity Relationship of New Pyrimidinamine Derivatives Containing an Aryloxy Pyridine Moiety
  作者：Aiying Guan、Changling Liu、Wei Chen、Fan Yang、Yong Xie、Jinbo Zhang、Zhinian Li、Mingan Wang

  DOI：10.1021/acs.jafc.6b05580

  日期：2017.2.15

  agrochemical lead compounds due to its unique mode of action, novel chemical structure, and lack of reported resistance. To develop a new pyrimidinamine fungicide effective against cucumber downy mildew (CDM), a series of new pyrimidinamine derivatives containing an aryloxy pyridine moiety were designed and synthesized by employing the recently reported intermediate derivatization method (IDM). The structures

  由于嘧啶胺的独特作用方式，新颖的化学结构和缺乏报道的抗药性，因此是发现农用化学先导化合物的理想模板。为了开发对黄瓜霜霉病（CDM）有效的新型嘧啶胺杀菌剂，通过使用最近报道的中间体衍生化方法（IDM）设计并合成了一系列含有芳氧基吡啶部分的新型嘧啶胺衍生物。所有化合物的结构均通过1 H NMR，元素分析，HRMS和X射线衍射鉴定。生物测定表明，某些标题化合物对CDM表现出优异的杀真菌活性。化合物9的活性最高（EC 50= 0.19 mg / L），明显优于市售杀菌剂diflumetorim，flumorph和cyazofamid。探索了合成的嘧啶胺的结构与杀菌活性之间的关系。研究表明，化合物9是有希望的杀真菌剂，可用于进一步开发。
• THIOPHENE DERIVATIVES AS PPAR AGONISTS I
  申请人：Ayscough Andrew

  公开号：US20100063065A1

  公开（公告）日：2010-03-11

  The invention discloses compounds of formula (I); wherein: R is a carboxylic acid or a derivative thereof; R 1 is alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, alkylthio, halo or trihalomethyl; R 2 is aryl, heteroaryl, arylalkyl or heteroarylalkyl; R 3 is H or F; and L is a linking group comprising a chain of from 2 to 8 atoms linking R and the carbonyl group (A); and pharmaceutically acceptable derivatives thereof, useful for treating disorders mediated by peroxisome-proliferator-activated receptor (PPAR) subtype δ (PPARδ). The compounds of the invention are therefore useful in the treatment of metabolic syndrome, obesity, type-II diabetes, dyslipidemia, wound healing, inflammation, neurodegenerative disorders and multiple sclerosis.

  本发明揭示了式(I)的化合物;其中：R是羧酸或其衍生物; R1是烷基，烯基，炔基，环烷基，烷氧基，烷硫基，卤素或三卤甲基; R2是芳基，杂环芳基，芳基烷基或杂环芳基烷基; R3是H或F; L是一个链接基团，包括从2到8个原子的链连接R和羰基(A);以及其药学上可接受的衍生物，用于治疗通过过氧化物酶体增殖物激活受体(PPAR)亚型δ (PPARδ)介导的疾病。因此，本发明的化合物在代谢综合征、肥胖症、2型糖尿病、脂质代谢异常、伤口愈合、炎症、神经退行性疾病和多发性硬化症的治疗中有用。
• 1-SUBSTITUTED 4-ARYLPIPERAZINE AS KAPPA OPIOID RECEPTOR ANTAGONISTS
  申请人：RESEARCH TRIANGLE INSTITUTE

  公开号：US20150005315A1

  公开（公告）日：2015-01-01

  Provided are compounds represented by the formula: where R, Y 3 , R 1 , R 2 , R 3 , R 4 , R 6 , G, R 7 , E 1 , E 2 , A, B, W, X, Y and Z are as defined herein.

  提供的化合物由以下公式表示：其中R，Y3，R1，R2，R3，R4，R6，G，R7，E1，E2，A，B，W，X，Y和Z的定义如下。