Ethyl 4-phenylpyridine-3-carboxylate | 40541-76-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: Ethyl 4-phenylpyridine-3-carboxylate
• 英文别名: 4-phenylnicotinic acid ethyl ether；ethyl 4-phenylnicotinate；4-phenyl-nicotinic acid ethyl ester；3-Pyridinecarboxylic acid, 4-phenyl-, ethyl ester
• CAS: 40541-76-2
• 化学式: C₁₄H₁₃NO₂
• 分子量: 227.263
• InChiKey: SFGNKGXOZFYBEE-UHFFFAOYSA-N

物化性质

• 沸点：
  356.5±30.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Ethyl 4-phenylpyridine-3-carboxylate 在 2,2,6,6-四甲基哌啶氧化物 、 碘苯二乙酸 、 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 1.5h， 生成 N-(3,5-bis(trifluoromethyl)benzyl)-N-((4-phenylpyridin-3-yl)methyl)cyclohexanecarboxamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of a novel class of potent TGR5 agonists based on a 4-phenyl pyridine scaffold

  摘要：

  TGR5, a GPCR, is involved in energy and glucose homeostasis, and as such, is a target for the treatment of diabetes, obesity and other metabolic syndromes. A new class of TGR5 agonists based on a 4-phenyl pyridine scaffold was designed, synthesized and evaluated in vitro and in vivo. Extensive structure activity relationship studies are reported herein. The most potent compounds 15a, 18b and 18c showed comparable activity with the lead compound 2. 15a had the best potency in vitro but displayed an pharmacokinetic profile and was found to be ineffective during an oral glucose tolerance test in imprinting control region mice at a dose of 50 mg/kg. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.07.050
• 作为产物：
  描述：

  烟酸乙酯 在 copper(l) iodide 作用下， 以 四氢呋喃 为溶剂， 反应 672000.67h， 生成 Ethyl 4-phenylpyridine-3-carboxylate
  参考文献：
  名称：

  First Rotameric Anti Dimers and 3,9-Diazatetraasteranes from Unsymmetrically Substituted N-Acyl and N-Acyloxy-4-aryl-1,4-dihydropyridines

  摘要：

  A series of unsymmetrically substituted N-acyl- and N-acyloxy-1,4-dihydropyridines (1) have been photochemically investigated. On irradiating the crystals of one derivative (la) containing centrosymmetrical pairs of molecules with a distance of 3.894(3) Angstrom between the potentially reacting double bonds favorable for a photodimerisation reaction, the formation of an anti-dimer (2a) was observed. Two other solid derivatives (1b, c) merely decomposed on irradiation to give substituted pyridine compound (3). Solution irradiation of 1,4-dihydropyridines (1) led to the centrosymmetric cage compounds 3,9-diazatetraasteranes (4) and to anti dimers (2) as main products, both existing as rotamers. Symmetric as well as rotameric properties of selected compounds (4) have been demonstrated by X-Ray crystal structure analysis and H-1 NMR spectroscopy.

  DOI：

  10.3987/com-01-9423

文献信息

• Design, Synthesis, and Structure-Activity Relationships of 3,4,5-Trisubstituted 4,5-Dihydro-1,2,4-oxadiazoles as TGR5 Agonists
  作者：Junjie Zhu、Yangliang Ye、Mengmeng Ning、Attila Mándi、Ying Feng、Qingan Zou、Tibor Kurtán、Ying Leng、Jianhua Shen

  DOI：10.1002/cmdc.201300144

  日期：2013.7

  By thorough analysis of diverse structures of published TGR5 agonists, a hypothetical ligand‐based pharmacophore model was built, and a new class of potent TGR5 agonists, based on the novel 3,4,5‐trisubstituted 4,5‐dihydro‐1,2,4‐oxadiazole core, was discovered by rational design. Three distinct synthetic methods for constructing 4,5‐dihydro‐1,2,4‐oxadiazoles and extensive structure–activity relationship

  鉴于其在能量和葡萄糖稳态中的介导作用，G蛋白偶联胆汁酸受体1（TGR5）被认为是治疗2型糖尿病和其他代谢性疾病的潜在靶标。通过对已发表的TGR5激动剂的各种结构进行全面分析，建立了一个假设的基于配体的药效团模型，并基于新型3,4,5-三取代的4,5-二氢-1，2来开发了一类新型的强效TGR5激动剂。 ，4-恶二唑核是通过合理设计发现的。本文报道了三种不同的合成方法来构建4,5-二氢-1,2,4-恶二唑和广泛的结构-活性关系研究。化合物（R）-54 n，其结构是通过单晶X-射线衍射和量子化学固态TDDFT-ECD计算确定，显示出最好的效力，用EC 50为1.4的n值中号朝向hTGR5。它在体外的有利特性值得进一步研究。
• Observations on the DDQ Oxidation of 1-Acyldihydropyridines - A Synthetic Application
  作者：Debra J. Wallace、Andrew D. Gibb、Ian F. Cottrell、Derek J. Kennedy、Karel M. J. Brands、Ulf H. Dolling

  DOI：10.1055/s-2001-17509

  日期：——

  A synthetic application of the rate difference in oxidation of regioisomerically substituted N-acyldihydropyridines is reported. This has allowed for isolation of pure 4-substituted pyridine isomers without the need for chromatography. Diels-Alder adducts between a dihydropyridine and DDQ were isolated and formation of novel hydroquinone ethers was also observed during some reactions.

  报道了区域异构取代的N-酰基二氢吡啶氧化速率差异的综合应用。这一方法使得无需色谱分离即可获得纯的4-取代吡啶异构体。在某些反应中，二氢吡啶与DDQ的Diels-Alder加合物被分离出来，并且观察到了新型的氢醌醚的形成。
• Regioselective addition of organomagnesium reagents to N-silyl activated nicotinic acid esters—a convenient method for the synthesis of 4,4-disubstituted 1,4-dihydronicotinates
  作者：Christian A. Sperger、Klaus T. Wanner

  DOI：10.1016/j.tet.2009.05.008

  日期：2009.7

  The addition of RMgX or R2Mg to nicotinic acid esters, activated with triisopropylsilyl triflate, was investigated. The regioselectivity of this reaction, where 4-unsubstituted and 4-substituted pyridine derivatives were employed as starting materials, was examined. Depending on the structure of the organomagnesium reagent varying ratios of 1,2-, 1,4-, and 1,6-regioisomers were obtained but in any

  研究了将RMgX或R 2 Mg添加到被三氟甲磺酸三异丙基甲硅烷基酯活化的烟酸酯中。检查了该反应的区域选择性，其中使用4-未取代的和4-取代的吡啶衍生物作为起始原料。取决于有机镁试剂的结构，获得了1,2-，1,4-和1,6-区域异构体的不同比率，但是在任何情况下1,4-加成产物显然都是主要的。异构体纯加成产物与LiOH的甲硅烷基化可提供稳定的4,4-二取代的二氢吡啶，这些化合物很容易用卤代烷以高收率进行N-烷基化。此外，显示出所获得的二氢吡啶的甲硅烷基保护基可以容易地被酰基取代。
• Aza-Wittig reaction of N-vinylic phosphazenes with carbonyl compounds. Azadiene-mediated synthesis of dihydropyridines and pyridines
  作者：Francisco Palacios、Gloria Rubiales

  DOI：10.1016/0040-4039(96)01352-4

  日期：1996.8

  diphenylmethylphosphine 4 with carbonyl compounds leads to the formation of 2-azadienes derived from β-aminoacids 5. Dimerization of 2-azadienes 5c,d and reaction of compounds 5 with phosphazene 4 or enemine 6 affords substituted dihydropyridines 7 and 8. Aza-Wittig reaction of phosphazenes 4 with α,β-unsaturated aldehydes gives 3-azatrienes 12, which are easily converted into pyridines 13.

  衍生自二苯基甲基膦4的N-乙烯基磷腈与羰基化合物的Aza-Wittig反应导致衍生自β-氨基酸5的2-氮杂二烯形成。2-氮杂二烯5c，d的二聚和化合物5与磷腈4或亚胺6的反应，得到取代的二氢吡啶7和8。磷腈4与α，β-不饱和醛的Aza-Wittig反应产生3-氮杂三酮12，该氮杂三氮烯12易于转化为吡啶13。
• Identification and Characterization of m1 Selective Muscarinic Receptor Antagonists
  作者：Corinne E. Augelli-Szafran、C. John Blankley、Juan C. Jaen、David W. Moreland、Carrie B. Nelson、Jan R. Penvose-Yi、Roy D. Schwarz、Anthony J. Thomas

  DOI：10.1021/jm980067l

  日期：1999.2.1

  A series of esters of 1,4-disubstituted tetrahydropyridine carboxylic acids (I) has been synthesized and characterized as potential mi selective muscarinic receptor antagonists. The affinity of these compounds for the five human muscarinic receptor subtypes (Hm1-Hm5) was determined by the displacement of [H-3]-NMS binding using membranes from transfected Chinese hamster ovarian cells. One of the most potent and selective compounds of this series is an analogue of I [11, R-1 = (CH2)(5)CH3], which has an IC50 value of 27.3 nM at the m1 receptor and possesses 100-fold (m2), 48-fold (m3), 74-fold (m4), and 19-fold (m5) selectivities at the other receptors. Thus, this analogue appears to be more selective on the basis of binding than the prototypical mi antagonist, pirenzepine. Functional data, such as the inhibition of carbachol-stimulated phosphatidylinositol hydrolysis, on selected analogues confirmed the muscarinic antagonistic properties of this chemical series.