5-(4-fluoro-phenyl)-4-(4-pyridyl)-imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(4-fluoro-phenyl)-4-(4-pyridyl)-imidazole
• 英文别名: 5-(4-fluoro-phenyl)-4-(pyridin-4-yl)-imidazole；4-(4-Fluorophenyl)-5-(pyridin-4-yl)-1H-imidazole；4-[4-(4-fluorophenyl)-1H-imidazol-5-yl]pyridine
• 化学式: C₁₄H₁₀FN₃
• 分子量: 239.252
• InChiKey: MAOSUPNJVJGJEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• 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：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-fluoro-phenyl)-4-(4-pyridyl)-imidazole 在 正丁基锂 、 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 生成 2-[5-(4-Fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-propan-2-ol
  参考文献：
  名称：

  SAR of 4-hydroxypiperidine and hydroxyalkyl substituted heterocycles as novel p38 map kinase inhibitors

  摘要：

  The 4-hydroxypiyeridine substituent was found to confer high p38 selectivity devoid of COX-1 affinity, when attached to a series of pyridinyl substituted heterocycles. Pyridinyloxazole 11 showed a promising in vivo profile with bioavailability of 64% and ED50 in rat collagen induced arthritis of 10 mg/kg po bid. In contrast to pyridinylimidazoles such as SE 203580, 11 did not inhibit human cytochrome P450 isoenzymes. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00200-6
• 作为产物：
  描述：

  4-溴吡啶 在 bis-triphenylphosphine-palladium(II) chloride 盐酸 、 sodium carbonate 作用下， 以 甲醇 、 乙醇 、 xylene 为溶剂， 反应 5.0h， 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

文献信息

• Rh(I)-Catalyzed Arylation of Heterocycles via C−H Bond Activation:  Expanded Scope through Mechanistic Insight
  作者：Jared C. Lewis、Ashley M. Berman、Robert G. Bergman、Jonathan A. Ellman

  DOI：10.1021/ja0748985

  日期：2008.2.1

  A practical, functional group tolerant method for the Rh-catalyzed direct arylation of a variety of pharmaceutically important azoles with aryl bromides is described. Many of the successful azole and aryl bromide coupling partners are not compatible with methods for the direct arylation of heterocycles using Pd(0) or Cu(I) catalysts. The readily prepared, low molecular weight ligand, Z-1-tert-butyl-2

  描述了一种实用的、官能团耐受的方法，用于各种药学上重要的唑类与芳基溴化物的 Rh 催化直接芳基化。许多成功的唑和芳基溴偶联伙伴与使用 Pd(0) 或 Cu(I) 催化剂直接芳基化杂环的方法不兼容。容易制备的低分子量配体 Z-1-叔丁基-2,3,6,7-四氢膦以双齿 P-烯烃方式与 Rh 配位，提供高活性但热稳定的芳基化催化剂，是这种方法的成功至关重要。通过使用相应鏻的四氟硼酸盐，反应可以在手套箱外组装，无需纯化试剂或溶剂。反应也在四氢呋喃或二恶烷中进行，与大多数其他使用高沸点酰胺溶剂直接芳基化唑类的方法相比，这大大简化了产品的分离。反应在微波反应器中加热进行，在 2 小时内获得优异的产品收率。
• Formamide intermediates for the preparation of tri-substituted imidazole compounds with multiple therapeutic properties
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1227091A3

  公开（公告）日：2002-08-07

  The invention relates to a novel group of formamide compounds and a process for their preparation, useful in the preparation of tri-substituted imadazoles having multiple therapeutic properties.

  这项发明涉及一类新型的甲酰胺化合物及其制备方法，可用于制备具有多种治疗性能的三取代咪唑。
• Imidazolyl-cyclic acetals
  申请人：Aventis Pharma Limited

  公开号：US06602877B1

  公开（公告）日：2003-08-05

  Compounds of formula (I) are described in which R1 is optionally substituted heteroaryl; R2 is optionally substituted aryl or optionally substituted heteroaryl; R3 is a group —L1—R7 or —L2—R8 [where L1 is an optionally substituted alkylene linkage; R7 is hydrogen, aryl, cyano, cycloalkyl, heteroaryl, heterocycloalkyl, nitro, —S(O)nR9, —NHSO2R9, —C(═Z)OR10, —C(═Z)R10, —OR10, —N(R11)—C(═Z)R9, —NY1Y2, —SO2NY1Y2, —C(═Z)—NY1Y2, —N(R11)—C(═Z)—NY1Y2, —N(OR10)—C(═Z)—NY1Y2, —N(OR10)—C(═Z)R10, —C(═NOR10)R10, —C(═Z)NR10OR12, —N(R11)—C(═NR13)—NY1Y2 or —N(R11)—C(═Z)OR11; L2 is a direct bond or a straight- or branched-carbon chain comprising from 2 to about 6 carbon atoms and contains a double or triple carbon-carbon bond; and R8 is hydrogen, aryl, cycloalkenyl, cycloalkyl, heteroaryl or heterocycloalkyl]; R4 is a group —L3—R14 [where L3 is a direct bond or an optionally substituted alkylene linkage and R14 is hydrogen, alkyl, azido, hydroxy, alkoxy, aryl, arylalkyloxy, aryloxy, carboxy (or an acid bioisostere), cycloalkyloxy, heteroaryl, heteroarylalkyloxy, heteroaryloxy, heterocycloalkyl, heterocycloalkyloxy, nitro, —NY4Y5, —N(R10)—C(═Z)—R15; —N(R10)—C(═Z)—L4—R16, —NH—C(═Z)—NH—R15, —NH—C(═Z)—NH—L4—R16, —N(R10)—SO2—R15, —N(R10)—SO2—L4—R16, —S(O)nR9, —C(═Z)—NY4Y5 or —C(═Z)—OR9]; R5 is hydrogen, alkyl or hydroxyalkyl; or R4 and R5, when attached to the same carbon atom, may form with the said carbon atom a cycloalkyl, cycloalkenyl or heterocycloalkyl ring or a group C═CH2; R6 is hydrogen or alkyl; and m is zero or an integer 1 or 2; and N-oxides thereof, and their prodrugs; and pharmaceutically acceptable salts and solvates (e.g. hydrates) of compounds of formula (I) and N-oxides thereof, and their prodrugs. The compounds are TNF inhibitors and are useful as pharmaceuticals.

  式（I）的化合物描述如下：其中R1是可选择取代的杂环芳基；R2是可选择取代的芳基或可选择取代的杂环芳基；R3是一个基团—L1—R7或—L2—R8【其中L1是可选择取代的烷基链；R7是氢、芳基、氰基、环烷基、杂环芳基、杂环烷基、硝基、—S(O)nR9、—NHSO2R9、—C(═Z)OR10、—C(═Z)R10、—OR10、—N(R11)—C(═Z)R9、—NY1Y2、—SO2NY1Y2、—C(═Z)—NY1Y2、—N(R11)—C(═Z)—NY1Y2、—N(OR10)—C(═Z)—NY1Y2、—N(OR10)—C(═Z)R10、—C(═NOR10)R10、—C(═Z)NR10OR12、—N(R11)—C(═NR13)—NY1Y2或—N(R11)—C(═Z)OR11；L2是直接键或由2到约6个碳原子组成的直链或支链碳链，含有双键或三键碳-碳键；R8是氢、芳基、环烯基、环烷基、杂环芳基或杂环烷基】；R4是一个基团—L3—R14【其中L3是直接键或可选择取代的烷基链，R14是氢、烷基、叠氮基、羟基、烷氧基、芳基、芳基烷氧基、芳氧基、羧基（或酸生物等构异体）、环烷氧基、杂环芳基、杂环芳基烷氧基、杂环芳氧基、杂环烷基、杂环烷氧基、硝基、—NY4Y5、—N(R10)—C(═Z)—R15；—N(R10)—C(═Z)—L4—R16、—NH—C(═Z)—NH—R15、—NH—C(═Z)—NH—L4—R16、—N(R10)—SO2—R15、—N(R10)—SO2—L4—R16、—S(O)nR9、—C(═Z)—NY4Y5或—C(═Z)—OR9】；R5是氢、烷基或羟基烷基；或者R4和R5，当连接到同一碳原子时，可以与所述碳原子形成环烷基、环烯基或杂环烷基环或基团C═CH2；R6是氢或烷基；m为零或整数1或2；以及其N-氧化物，以及它们的前药；以及式（I）的化合物及其N-氧化物的药学上可接受的盐和溶剂（例如水合物），以及它们的前药。这些化合物是肿瘤坏死因子抑制剂，可用作药物。
• Imine intermediates for the preparation of trisubstituted imidazole compounds with multiple therapeutic properties
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1229035A1

  公开（公告）日：2002-08-07

  The invention relates to a novel group of iminc compounds and a process for their preparation, useful in the preparation of tri-substituted imadazoles having multiple therapeutic properties.

  这项发明涉及一类新型的iminc化合物及其制备方法，可用于制备具有多种治疗性能的三取代咪唑。
• Isonitrile intermediates for the preparation of tri-substituted imidazole compounds with multiple therapeutic properties
  申请人：SmithKline Beecham Corporation

  公开号：EP1227092A3

  公开（公告）日：2002-08-07

  The invention relates to a novel group of isonitrile compounds and a process for their preparation, useful in the preparation of tri-substituted imadazoles having multiple therapeutic properties.

  这项发明涉及一类新型异腈化合物及其制备方法，可用于制备具有多种治疗性能的三取代咪唑。