2-(t-butyldimethylsilyloxy)-3'-chloro-2-(pyridin-4-yl)acetophenone | 226259-79-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(t-butyldimethylsilyloxy)-3'-chloro-2-(pyridin-4-yl)acetophenone
• 英文别名: 2-[Tert-butyl(dimethyl)silyl]oxy-1-(3-chlorophenyl)-2-pyridin-4-ylethanone
• CAS: 226259-79-6
• 化学式: C₁₉H₂₄ClNO₂Si
• 分子量: 361.944
• InChiKey: LXXHYOKVANEGDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.68
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(t-butyldimethylsilyloxy)-3'-chloro-2-(pyridin-4-yl)acetophenone 在 dipotassium peroxodisulfate 、 copper diacetate 、 ammonium acetate 、 溶剂黄146 作用下， 反应 18.67h， 生成 4-(3-Chlorophenyl)-2-(4-methylsulfinylphenyl)-5-(pyridin-4-yl)-1H-imidazole
  参考文献：
  名称：

  Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase

  摘要：

  Members of three classes of pyridinylimidazoles bind with varying affinities to CSBP (p38) kinase which is a member of a stress-induced signal transduction pathway. Based upon SAR and protein homology modeling, the pharmacophore and three potential modes of binding to the enzyme are presented. For a subset of pyridinylimidazoles, binding is shown to correlate with inhibition of CSBP kinase activity, whereas no significant inhibition of PKA, PKC alpha and ERK kinase activity is observed. Copyright (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(96)00212-x
• 作为产物：
  描述：

  4-吡啶甲醇 在 咪唑 、 lithium diisopropyl amide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.25h， 生成 2-(t-butyldimethylsilyloxy)-3'-chloro-2-(pyridin-4-yl)acetophenone
  参考文献：
  名称：

  Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase

  摘要：

  Members of three classes of pyridinylimidazoles bind with varying affinities to CSBP (p38) kinase which is a member of a stress-induced signal transduction pathway. Based upon SAR and protein homology modeling, the pharmacophore and three potential modes of binding to the enzyme are presented. For a subset of pyridinylimidazoles, binding is shown to correlate with inhibition of CSBP kinase activity, whereas no significant inhibition of PKA, PKC alpha and ERK kinase activity is observed. Copyright (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(96)00212-x

文献信息

• Design and Synthesis of Potent, Selective, and Orally Bioavailable Tetrasubstituted Imidazole Inhibitors of p38 Mitogen-Activated Protein Kinase
  作者：Nigel J. Liverton、John W. Butcher、Christopher F. Claiborne、David A. Claremon、Brian E. Libby、Kevin T. Nguyen、Steven M. Pitzenberger、Harold G. Selnick、Garry R. Smith、Andrew Tebben、Joseph P. Vacca、Sandor L. Varga、Lily Agarwal、Kim Dancheck、Amy J. Forsyth、Daniel S. Fletcher、Betsy Frantz、William A. Hanlon、Coral F. Harper、Scott J. Hofsess、Matthew Kostura、Jiunn Lin、Sylvie Luell、Edward A. O'Neill、Chad J. Orevillo、Margaret Pang、Janey Parsons、Anna Rolando、Yousif Sahly、Denise M. Visco、Stephen J. O'Keefe

  DOI：10.1021/jm9805236

  日期：1999.6.1

  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.
• Potent inhibitors of the MAP kinase p38
  作者：James R. Henry、Kenneth C. Rupert、John H. Dodd、Ignatius J. Turchi、Scott A. Wadsworth、Druie E. Cavender、Peter H. Schafer、John J. Siekierka

  DOI：10.1016/s0960-894x(98)00589-7

  日期：1998.12

  The MAP kinase p38 plays a key role in the biosynthesis of the inflammatory cytokines TNF-alpha and IL-1. We have developed a novel series of potent p38 inhibitors that could lead to new methods of treatment for inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease, (C) 1998 Elsevier Science Ltd. All rights reserved.
• Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase
  作者：Timothy F. Gallagher、George L. Seibel、Shouki Kassis、Jeffrey T. Laydon、Mary Jane Blumenthal、John C. Lee、Dennis Lee、Jeffrey C. Boehm、Susan M. Fier-Thompson、Jeffrey W. Abt、Margaret E. Soreson、Juanita M. Smietana、Ralph F. Hall、Ravi S. Garigipati、Paul E. Bender、Karl F. Erhard、Arnold J. Krog、Glenn A. Hofmann、Peter L. Sheldrake、Peter C. McDonnell、Sanjay Kumar、Peter R. Young、Jerry L. Adams

  DOI：10.1016/s0968-0896(96)00212-x

  日期：1997.1

  Members of three classes of pyridinylimidazoles bind with varying affinities to CSBP (p38) kinase which is a member of a stress-induced signal transduction pathway. Based upon SAR and protein homology modeling, the pharmacophore and three potential modes of binding to the enzyme are presented. For a subset of pyridinylimidazoles, binding is shown to correlate with inhibition of CSBP kinase activity, whereas no significant inhibition of PKA, PKC alpha and ERK kinase activity is observed. Copyright (C) 1997 Elsevier Science Ltd.