4-(2,4-diphenyl-1H-imidazole-5-yl)pyridine | 208641-25-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(2,4-diphenyl-1H-imidazole-5-yl)pyridine
• 英文别名: 4-(2,4-diphenyl-1H-imidazol-5-yl)pyridine
• CAS: 208641-25-2
• 化学式: C₂₀H₁₅N₃
• 分子量: 297.359
• InChiKey: YYQUGNLGTLHJFO-UHFFFAOYSA-N

物化性质

• 沸点：
  517.4±35.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-甲基-N-甲基苯甲酰胺 在 乙酸铵 、 copper diacetate 、 溶剂黄146 、 lithium diisopropyl amide 作用下， 反应 1.58h， 生成 4-(2,4-diphenyl-1H-imidazole-5-yl)pyridine
  参考文献：
  名称：

  Design and Synthesis of Potent, Selective, and Orally Bioavailable Tetrasubstituted Imidazole Inhibitors of p38 Mitogen-Activated Protein Kinase

  摘要：

  Novel potent and selective diarylimidazole inhibitors of p38 MAP (mitogen-activated protein) kinase are described which have activity in both cell-based assays of tumor necrosis factor-alpha (TNF-alpha) release and an animal model of rheumatoid arthritis; The SAR leading to the development of selectivity against c-Raf and JNK2 alpha 1 kinases is presented, with key features being substitution of the 4-aryl ring with m-trifluoromethyl and substitution of the 5-heteroaryl ring with a a-amino substituent. Cell-based activity was significantly enhanced by incorporation of a 4-piperidinyl moiety at the 2-position of the imidazole which also enhanced aqueous solubility. In general, oral bioavailability of this class of compounds was found to be poor unless the imidazole was methylated on nitrogen. This work led to identification of 48, a potent (p38 MAP kinase inhibition IC50 0.24 nM) and selective p38 MAP kinase inhibitor which inhibits lipopolysaccharide-stimulated release of TNF-alpha from human blood with an IC50 2.2 nM, shows good oral bioavailability in rat and rhesus monkey, and demonstrates significant improvement in measures of disease progression in a rat adjuvant-induced arthritis model.

  DOI：

  10.1021/jm9805236

文献信息

• Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles
  作者：C. Frank Lee、Aleksandra Holownia、James M. Bennett、Jonathan M. Elkins、Jeffrey D. St. Denis、Shinya Adachi、Andrei K. Yudin

  DOI：10.1002/anie.201611006

  日期：2017.5.22

  accessible through commercially available starting materials, enables a modular approach for the synthesis of imidazoles. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium-catalyzed cross-coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds

  本文描述了草酰硼酸酯结构单元的制备及其在杂环的构建中的应用。通过商业上可获得的起始原料容易获得的草酰单元使得能够以模块化的方式合成咪唑。将各种芳族，杂芳族和烷基羧醛与草酰硼酸酯缩合，以区域控制的方式提供取代的硼基咪唑。随后钯与卤代芳烃的交叉偶联提供了所需的三取代的咪唑支架。为了证明这些支架的实用性，合成了丝氨酸/苏氨酸蛋白激酶STK10的有效抑制剂。
• [EN] IMIDAZOLES FOR TREATING CYTOKINE MEDIATED DISEASE<br/>[FR] IMIDAZOLES ACTIVES CONTRE LES MALADIES TRANSMISES PAR LA CYTOKINE
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：WO1995003297A1

  公开（公告）日：1995-02-02

  (EN) Novel 2,4,5-triaryl imidazole compounds and compositions for use in therapy, such as cytokine mediated diseases.(FR) Ces nouveaux composés et compositions à base de 2,4,5-triaryle-imidazole sont destinés aux thérapies de traitement des maladies du type de celles qui sont transmises par la cytokine.

  (中文) 这些新的2,4,5-三芳基咪唑化合物和组合物用于治疗细胞因子介导的疾病，如细胞因子介导的疾病。
• Novel compounds
  申请人：SmithKline Beecham Corporation

  公开号：US20030064997A1

  公开（公告）日：2003-04-03

  Novel 2,4,5-triaryl imidazole compounds and compositions for use in therapy.

  小说2,4,5-三芳基咪唑化合物及其在治疗中的应用组成物。
• 2,4,5-tri-substituted azole-based casein kinase 1 inhibitors as inducers for cardiomyogenesis
  申请人：AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

  公开号：US10865384B2

  公开（公告）日：2020-12-15

  This invention relates to a method for inducing or enhancing the differentiation of pluripotent stem cells into cardiomyocyte via casein kinase 1 inhibition said method comprising culturing the stem cells in the presence of a medium comprising a casein kinase 1 inhibitor of the formula (I) or (II) or a stereoisomer, tautomer, or a salt thereof wherein R1, R2 and R3 independently from another represent hydrogen, optionally substituted alkyl, alkenyl, alkynyl, heterocyclyl, heteroaryl or aryl; X represents NR4, O or S; and R4 represents hydrogen, optionally substituted alkyl, alkenyl, alkynyl, heterocyclyl, heteroaryl or aryl. The method can be used in the late phase of stem cell differentiation and in the compounds of formula (I) or (II) in combination with other small molecules can lead to especially high differentiation of stem cells into cardiomyocytes. The invention further relates to novel compounds which can be used in the method of the invention and kits for stem cell differentiation.

  本发明涉及一种通过抑制酪蛋白激酶1诱导或增强多能干细胞向心肌细胞分化的方法，所述方法包括在含有式(I)或(II)的酪蛋白激酶1抑制剂或其立体异构体、同系物或盐的培养基存在下培养干细胞，其中R1、R2和R3独立地代表氢、任选取代的烷基、烯基、炔基、杂环基、杂芳基或芳基；X 代表 NR4、O 或 S；R4 代表氢、任选取代的烷基、烯基、炔基、杂环基、杂芳基或芳基。该方法可用于干细胞分化的后期阶段，式（I）或（II）化合物与其他小分子结合使用，可使干细胞分化为心肌细胞的程度特别高。本发明进一步涉及可用于本发明方法和干细胞分化试剂盒的新型化合物。
• Synthesis of Substituted Imidazoles via Organocatalysis
  作者：Doug E. Frantz、Louis Morency、Arash Soheili、Jerry A. Murry、Edward J. J. Grabowski、Richard D. Tillyer

  DOI：10.1021/ol0498803

  日期：2004.3.1

  A one-pot synthesis of substituted imidazoles is described. The cornerstone of this methodology involves the thiazolium-catalyzed addition of an aldehyde to an acyl Imine to generate the corresponding alpha-ketoamide in situ followed by ring closure to the imidazole in a one-pot sequence. The extension of this methodology to the one-pot synthesis of substituted oxazoles and thiazoles is also described.