N-{4-[2-cyano-2-(4-fluorophenyl)acetyl]pyridin-2-yl}acetamide | 452056-79-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-{4-[2-cyano-2-(4-fluorophenyl)acetyl]pyridin-2-yl}acetamide
• 英文别名: 2-cyano-2-(4-fluorophenyl)-1-(2-acetamido-4-pyridyl)ethanone；N-[4-[2-cyano-2-(4-fluorophenyl)acetyl]pyridin-2-yl]acetamide
• CAS: 452056-79-0
• 化学式: C₁₆H₁₂FN₃O₂
• 分子量: 297.289
• InChiKey: WRAMFBNOYKKPPJ-UHFFFAOYSA-N

物化性质

• 熔点：
  257 °C
• 沸点：
  566.6±50.0 °C(Predicted)
• 密度：
  1.334±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  82.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-{4-[2-cyano-2-(4-fluorophenyl)acetyl]pyridin-2-yl}acetamide 在 4-二甲氨基吡啶 、 氢溴酸 、 sodium methylate 、 亚硝酸异戊酯 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 45.0h， 生成 N-{4-[5-(4-fluorophenyl)-1-oxy-3-methyl-3H-imidazol-4-yl]pyridin-2-yl}acetamide
  参考文献：
  名称：

  Tetrasubstituted Imidazole Inhibitors of Cytokine Release:  Probing Substituents in the N-1 Position

  摘要：

  We prepared novel 1,2,4,5-tetrasubstituted imidazole derivatives with high anti-inflammatory activity by using our previously described regiospecific synthesis. Systematic optimization of the imidazole N-1 substituent resulted in compound 9b that potently inhibited the mitogen-activated protein kinase p38 (p38 IC50 = 0.218 muM) as well as the release of the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor alpha. (TNFalpha) from human whole blood after stimulation with LPS. Furthermore, compound 9b exhibited reduced cytochrome P450 interaction in comparison with SB203580. This result is particularly important, since cytochrome P450 interaction is observed for some p38 inhibitors and in turn can potentially cause drug-drug interaction or lead to other hepatic changes such as P450 enzyme induction.

  DOI：

  10.1021/jm0496584
• 作为产物：
  描述：

  2-(乙酰氨基)-4-甲基吡啶 在 potassium permanganate 、 N,N'-羰基二咪唑 作用下， 以 水 为溶剂， 生成 N-{4-[2-cyano-2-(4-fluorophenyl)acetyl]pyridin-2-yl}acetamide
  参考文献：
  名称：

  Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases

  摘要：

  The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38 alpha MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs, and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha release. For reconfirming the findings of the animal studies when administering 1 to healthy human volunteers, a phase I clinical trial was conducted. Apart from further information regarding the pharmacokinetic and pharmacodynamic characteristics of 1, it was demonstrated that dual inhibition of p38 alpha MAPK and PDE4 is able to synergistically attenuate the excessive anti-inflammatory response.

  DOI：

  10.1021/acs.jmedchem.6b01647

文献信息

• Imidazole compounds having an antiinflammatory effect
  申请人：MERCKLE GMBH

  公开号：EP1894925A1

  公开（公告）日：2008-03-05

  The invention relates to 2-sulfinyl- or 2-sulfonyl-substituted imidazole derivatives of the formula I in which the radicals R1, R2, R3 and R4 have the meaning indicated in the description. The compounds of the invention have an immunomodulating and/or cytokine release-inhibiting effect and are therefore suitable for the treatment of disorders associated with an impairment of the immune system.

  这项发明涉及公式I的2-磺酰基或2-磺酰基取代的咪唑衍生物， 其中基团R1、R2、R3和R4具有描述中指示的含义。该发明的化合物具有免疫调节和/或细胞因子释放抑制作用，因此适用于治疗与免疫系统功能障碍相关的疾病。
• IMIDAZOLE COMPOUNDS HAVING AN ANTIINFLAMMATORY EFFECT
  申请人：Albrecht Wolfgang

  公开号：US20100069436A1

  公开（公告）日：2010-03-18

  The invention relates to imidazole derivatives of the Formula (I) in which the radicals R 1 , R 2 , R 3 , R 4 and R 5 have the meanings indicated in the description. The compounds of the invention have an immunomodulating and/or cytokine release-inhibiting effect and are therefore suitable for the treatment of disorders associated with an impairment of the immune system.

  本发明涉及式（I）的咪唑衍生物，其中基团R1、R2、R3、R4和R5具有说明书中指示的含义。该发明的化合物具有免疫调节和/或细胞因子释放抑制作用，因此适用于治疗与免疫系统受损有关的疾病。
• WO2006/89798
  申请人：——

  公开号：——

  公开（公告）日：——
• 2-THIO-SUBSITUIERTE IMIDAZOLDERIVATIVE UND IHRE VERWENDUNG IN DER PHARMAZIE
  申请人：MERCKLE GMBH

  公开号：EP1362045A2

  公开（公告）日：2003-11-19
• 2-SULFINYL- AND 2-SULFONYL-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE AS CYTOKINE INHIBITORS
  申请人：MERCKLE GMBH

  公开号：EP1853581A1

  公开（公告）日：2007-11-14