4-苯基吡啶-3-羧醛 | 46268-56-8

• 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
• 中文名称: 4-苯基吡啶-3-羧醛
• 英文名称: 4-phenyl-3-pyridinecarbaldehyde
• 英文别名: 4-phenyl-3-pyridinecarboxaldehyde；4-phenylpyridine-3-carboxaldehyde；4-phenylpyridine-3-carbaldehyde；4-phenyl-3-pyridinecarboxylate；4-phenyl-3-nicotinaldehyde；4-phenylnicotinaldehyde
• CAS: 46268-56-8
• 化学式: C₁₂H₉NO
• mdl: MFCD03001458
• 分子量: 183.21
• InChiKey: WMONEBTVHBSEMH-UHFFFAOYSA-N

物化性质

• 沸点：
  342.8±30.0 °C(Predicted)
• 密度：
  1.147±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  4-苯基吡啶-3-羧醛 在 三乙酰氧基硼氢化钠 、 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 、 乙腈 为溶剂， 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：

  4-氯吡啶-3-羧酸乙酯盐酸盐 在 四(三苯基膦)钯 、 2,2,6,6-四甲基哌啶氧化物 、 碘苯二乙酸 、 二异丁基氢化铝 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 13.5h， 生成 4-苯基吡啶-3-羧醛
  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

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。
• 五元唑类杂环化合物及其制备方法、药物组合 物和用途
  申请人：中国科学院上海药物研究所

  公开号：CN103864754B

  公开（公告）日：2016-12-21

  本发明涉及一类如下通式（I）所示的五元唑类杂环化合物、其制备方法、药物组合物及其在制备预防或治疗由TGR5介导的疾病的药物中的用途。
• Vilsmeier–Haack reaction of tertiary alcohols: formation of functionalised pyridines and naphthyridines
  作者：Ajith Dain Thomas、Chitoorthekkathil V. Asokan

  DOI：10.1039/b105634b

  日期：2001.10.11

  which on ammonium acetate-induced cyclisation afford 4-arylnicotinaldehydes in good yields. Tertiary alcohols derived from aliphatic or alicyclic ketones by the addition of methyl Grignard are converted into substituted pyridines and naphthyridines by the action of Vilsmeier's reagent in N,N-dimethylformamide followed by nucleophile-assisted cyclisation in the presence of ammonium acetate.

  2-芳基丙烷-2-醇的Vilsmeier-Haack反应通过多次亚氨基烷基化反应进行，导致形成共轭亚胺盐，该盐在乙酸铵诱导的环化反应中以良好的收率得到4-芳基烟碱醛。在N，N-二甲基甲酰胺中，通过Vilsmeier试剂的作用，由脂肪族或脂环族酮通过添加甲基格利雅（Grignard）衍生而来的叔醇转化为取代的吡啶和萘啶，然后在乙酸铵存在下进行亲核试剂辅助的环化反应。
• NOVEL SMALL MOLECULE POTENTIATORS OF METABOTROPIC GLUTAMATE RECEPTORS I
  申请人：Braje Wilfried

  公开号：US20110245232A1

  公开（公告）日：2011-10-06

  The present invention relates to small molecule potentiators of metabotropic receptors, in particular of the mGlu2 receptor. The present invention also relates to the use of these compounds for the prevention or treatment of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The present invention thus provides compounds of formula I wherein X 2 is N or C—R 2 , X 3 is N or C—R 3 , X 4 is N or C—R 4 provided that none or one of X 2 , X 3 or X 4 is N; Y 1 is N, C or C—R 5 , Y 2 is N, C or C—R 6 , Y 3 is N, C or C—R 7 , Y 4 is N, C or C—R 8 provided that only the moiety Y 1 , Y 2 , Y 3 or Y 4 to which Z is bound is C and further provided at most one of Y 1 , Y 2 , Y 3 or Y 4 is N; Z is O, S, S(O), S(O) 2 or NR Z ; Q is CH 2 or CH 2 CH 2 , where one or two of the hydrogen atoms in CH 2 or CH 2 CH 2 may be replaced by halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl; R 1 is inter alia hydrogen, halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 4 -haloalkoxy, C 3 -C 8 -cycloalkyl, a radical NR 1a R 1b , C-bound 3- to 7-membered, saturated heterocyclyl having 1 or 2 nitrogen atoms and 0 or 1 heteroatoms, selected from O and S, as ring members, aryl, aryl-CH 2 , aryloxy, hetaryl, hetaryloxy or hetaryl-CH 2 , wherein the heterocyclyl, aryl and hetaryl rings ring in the last six radicals themselves are unsubstituted or carry 1, 2, 3, 4 or 5 identical or different radicals R 1c ; R 2 , R 3 and R 4 are, inter alia, selected from hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, phenyl, C 1 -C 4 -haloalkoxy, a radical (CH 2 ) n NR′R″; R 5 , R 6 , R 7 , R 8 are, independently of each other, selected from hydrogen, halogen, etc.; R a is C 3 -C 6 -cycloalkyl, C 1 -C 6 -haloalkyl or C 1 -C 6 -alkyl, which is unsubstituted or carries one radical selected from C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy and a radical NR a1 R a2 , R b is hydrogen, halogen or C 1 -C 4 -alkyl; and the N-oxides and the pharmaceutically acceptable salts thereof.

  本发明涉及代谢型受体的小分子增强剂，特别是mGlu2受体的增强剂。本发明还涉及这些化合物的使用，用于预防或治疗与谷氨酸功能障碍有关的神经和精神障碍以及代谢型谷氨酸受体参与的疾病。因此，本发明提供了式I的化合物，其中X2为N或C—R2，X3为N或C—R3，X4为N或C—R4，但X2、X3或X4中没有或只有一个为N；Y1为N、C或C—R5，Y2为N、C或C—R6，Y3为N、C或C—R7，Y4为N、C或C—R8，但只有Y1、Y2、Y3或Y4中的一个Y与Z相连的基团为C且最多只有一个Y为N；Z为O、S、S(O)、S(O)2或NRZ；Q为CH2或CH2CH2，其中CH2或CH2CH2中的一个或两个氢原子可以被卤素、C1-C4烷基或C1-C4卤代烷基取代；R1为氢、卤素、C1-C6烷基、C1-C6卤代烷基、C1-C6烷氧基、C1-C4卤代烷氧基、C3-C8环烷基、基团NR1aR1b、C-连接的3-至7-成员饱和杂环基，其中有1或2个氮原子和0或1个杂原子，选自O和S作为环成员，芳基、芳基-CH2、芳氧基、杂芳基、杂芳氧基或杂芳基-CH2，其中在最后六个基团中的杂环基、芳基和杂芳基环本身未取代或携带1、2、3、4或5个相同或不同的基团R1c；R2、R3和R4等，选自氢、卤素、C1-C4烷基、C1-C4卤代烷基、C3-C6环烷基、C1-C4烷氧基、C1-C4烷氧基-C1-C4-烷基、苯基、C1-C4卤代烷氧基、基团(CH2)nNR′R″；R5、R6、R7和R8独立地选自氢、卤素等；Ra为C3-C6环烷基、C1-C6卤代烷基或C1-C6烷基，未取代或携带选自C1-C4烷氧基、C1-C4卤代烷氧基和基团NRa1Ra2的一个基团；Rb为氢、卤素或C1-C4烷基；以及其N-氧化物和药学上可接受的盐。
• .omega.-(3-pyridyl)alkenamide derivatives and anti-allergenic
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US04778796A1

  公开（公告）日：1988-10-18

  Compounds of the formula: ##STR1## wherein X is alkylene or --(CR.sub.6 .dbd.CR.sub.7).sub.r -- wherein R.sub.6 is H, alkyl or phenyl, R.sub.7 is H, alkyl, cyano or phenyl, and r is 1 or 2; A is alkylene or alkylene interrupted by at least one double bond; R.sub.1 is H, halogen, alkyl, alkoxy, alkylthio, cycloalkyloxy, cycloalkylthio, alkoxycarbonyl, carboxy, phenyl, phenoxy, phenylthio, 3-pyridyloxy or 3-pyridylthio; R.sub.2 is H, hydroxy, alkanoyloxy or alkoxycarbonyloxy, or adjacent R.sub.1 and R.sub.2 may combine to form tetramethylene or --CH.sub.2 OCR.sub.8 R.sub.9 O-- (R.sub.8 and R.sub.9 are alkyl); R.sub.3 is H, alkyl or hydroxyalkyl; R.sub.4 is H or alkyl; R.sub.5 is phenyl, heteroaryl or --(CH.sub.2).sub.m --CHR.sub.10 R.sub.11 (R.sub.10 is H or phenyl, R.sub.11 is phenyl or pyridyl and m is 0 to 2); p is 0 or 1; and q is 2 or 3; the phenyl group or moiety being optionally substituted, and a salt thereof, process for the preparation thereof, and pharmaceutical composition containing the same. Said compounds and salts thereof show excellent antiallergic activity mainly through 5-lipoxygenase inhibiting activity, antihistamine activity and/or inhibitory activity against chemical mediator release and useful for treatment of allergic diseases.

  该公式化合物为：##STR1## 其中X为烷基或--(CR.sub.6.dbd.CR.sub.7).sub.r --，其中R.sub.6为H、烷基或苯基，R.sub.7为H、烷基、氰基或苯基，r为1或2；A为烷基或至少有一个双键的烷基；R.sub.1为H、卤素、烷基、烷氧基、烷硫基、环烷氧基、环烷硫基、烷氧羰基、羧基、苯基、苯氧基、苯硫基、3-吡啶氧基或3-吡啶硫基；R.sub.2为H、羟基、烷酰氧基或烷氧羰酰氧基，或相邻的R.sub.1和R.sub.2可以结合形成四亚甲基或--CH.sub.2 OCR.sub.8 R.sub.9 O--（其中R.sub.8和R.sub.9为烷基）；R.sub.3为H、烷基或羟基烷基；R.sub.4为H或烷基；R.sub.5为苯基、杂环芳基或--(CH.sub.2).sub.m --CHR.sub.10 R.sub.11（其中R.sub.10为H或苯基，R.sub.11为苯基或吡啶基，m为0到2）；p为0或1；q为2或3；苯基或基团可选择性地被取代；以及其盐、制备方法和含有它的药物组成物。所述化合物及其盐主要通过5-脂氧酶抑制活性、抗组胺活性和/或化学介质释放抑制活性表现出优异的抗过敏活性，并用于治疗过敏性疾病。