4-[5-(4-fluoro-phenyl)-3-[(2-(trimethylsilyl)ethoxy)methyl]-1H-imidazol-4-yl]-pyridine | 215303-25-6

• 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-[5-(4-fluoro-phenyl)-3-[(2-(trimethylsilyl)ethoxy)methyl]-1H-imidazol-4-yl]-pyridine
• 英文别名: 4-(4-fluorophenyl)-5-(pyridin-4-yl)-1-(2-(trimethylsilyl)-ethoxymethyl)-imidazole；4-(4-fluorophenyl)-5-(4-pyridyl)-1-(2-(trimethylsilyl)-ethoxymethyl)-imidazole；1-(2-(Trimethylsilyl)ethoxymethyl)-4-(4-fluorophenyl)-5-(4-pyridyl)imidazole；2-[[4-(4-fluorophenyl)-5-pyridin-4-ylimidazol-1-yl]methoxy]ethyl-trimethylsilane
• CAS: 215303-25-6
• 化学式: C₂₀H₂₄FN₃OSi
• 分子量: 369.514
• InChiKey: RTEHHLKYFIUUEN-UHFFFAOYSA-N

物化性质

• 沸点：
  475.9±45.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.06
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[5-(4-fluoro-phenyl)-3-[(2-(trimethylsilyl)ethoxy)methyl]-1H-imidazol-4-yl]-pyridine 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 5-(4-fluoro-phenyl)-4-(4-pyridyl)-imidazole
  参考文献：
  名称：

  邻氨基溴化萘作为制备二取代和三取代的咪唑的新型结构单元

  摘要：

  已经开发了三种新颖的基于咪唑的邻位溴化芳烃5a-c，用于区域选择性制备2,4,5-三-和4,5-二取代的咪唑。对于涉及有价值的芳基或杂芳基卤化物的Stille和Suzuki偶联，新的构建基块特别有吸引力，在这些偶联中，转化为同等的锡烷或硼烷/硼酸将是一个不可行的选择。

  DOI：

  10.1016/s0040-4039(98)01056-9
• 作为产物：
  描述：

  4-溴吡啶 在 bis-triphenylphosphine-palladium(II) chloride sodium carbonate 作用下， 以 甲醇 、 xylene 为溶剂， 反应 5.0h， 生成 4-[5-(4-fluoro-phenyl)-3-[(2-(trimethylsilyl)ethoxy)methyl]-1H-imidazol-4-yl]-pyridine
  参考文献：
  名称：

  邻氨基溴化萘作为制备二取代和三取代的咪唑的新型结构单元

  摘要：

  已经开发了三种新颖的基于咪唑的邻位溴化芳烃5a-c，用于区域选择性制备2,4,5-三-和4,5-二取代的咪唑。对于涉及有价值的芳基或杂芳基卤化物的Stille和Suzuki偶联，新的构建基块特别有吸引力，在这些偶联中，转化为同等的锡烷或硼烷/硼酸将是一个不可行的选择。

  DOI：

  10.1016/s0040-4039(98)01056-9

文献信息

• 2-substituted 4,5-diaryl imidazoles
  申请人：Novartis AG

  公开号：US06300347B1

  公开（公告）日：2001-10-09

  Novel 2-substituted 4,5-diaryl imidazoles are provided, in particular compounds of Formula I wherein R1, R2, R3 and R4 are as defined, in free or pharmaceutically-acceptable acid addition salt or physiologically-cleavable ester form, which have p38 MAP kinase (Mitogen Activated Protein Kinase) inhibiting activity. The compounds are used as pharmaceuticals for treating TNF&agr; and IL-1 mediated diseases such as rheumatoid arthritis and diseases of bone metabolism, e.g. osteoporosis.

  提供了一种新型的2-取代的4,5-二芳基咪唑类化合物，特别是公式I中的化合物，其中R1、R2、R3和R4如所定义，在自由或药学上可接受的酸盐或生理可降解酯形式中，具有抑制p38 MAP激酶（有丝分裂原激活蛋白激酶）活性。这些化合物被用作药物，用于治疗由TNFα和IL-1介导的疾病，如类风湿性关节炎和骨代谢疾病，例如骨质疏松症。
• The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy
  作者：Iain M. McLay、Frank Halley、John E. Souness、Jeffrey McKenna、Veronique Benning、Mark Birrell、Brenda Burton、Maria Belvisi、Alan Collis、Alex Constan、Martyn Foster、David Hele、Zaid Jayyosi、Mike Kelley、Chris Maslen、Glen Miller、Marie-Claude Ouldelhkim、Kenneth Page、Simon Phipps、Kenneth Pollock、Barry Porter、Andrew J. Ratcliffe、Elisabeth J. Redford、Stephen Webber、Bryan Slater、Veronique Thybaud、Nicola Wilsher

  DOI：10.1016/s0968-0896(00)00331-x

  日期：2001.2

  RPR132331, a 2-(2-dioxanyl)imidazole. was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes. An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A, a development candidate for the treatment of rheumatoid arthritis (RA). RPR200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM). It inhibits LPS-stimulated TNF alpha release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in Balb/c mice (ED50 = 6 mg/kg). At oral doses between 10 and 30 mg/kg/day it reduces the incidence and progression in the rat streptococcal cell wall (SCW) arthritis model when administered in either prophylactic or therapeutic dosing regimens. The compound, which is a mesylate salt and exists as a stable monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent chemical stability. The data from the SCW disease model suggests that RPR200765A could exhibit a profile of disease modifying activity in rheumatoid arthritis (RA) patients which is not observed with current drug therapies. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Vicinal bromostannanes as novel building blocks for the preparation of di- and trisubstituted imidazoles
  作者：Laszlo Revesz、Frédérique Bonne、Paschalia Makavou

  DOI：10.1016/s0040-4039(98)01056-9

  日期：1998.7

  imidazole-based vicinal bromostannanes 5a-c have been developed for the regioselective preparation of 2,4,5-tri- and 4,5-disubstituted imidazoles. The novel building blocks are particularly attractive for Stille and Suzuki couplings that involve valuable aryl or heteroaryl halides, where conversion to the equivalent stannanes or boranes/boronic acids would represent an inviable option.

  已经开发了三种新颖的基于咪唑的邻位溴化芳烃5a-c，用于区域选择性制备2,4,5-三-和4,5-二取代的咪唑。对于涉及有价值的芳基或杂芳基卤化物的Stille和Suzuki偶联，新的构建基块特别有吸引力，在这些偶联中，转化为同等的锡烷或硼烷/硼酸将是一个不可行的选择。