2-(tert-butyldimethylsilanyloxy)-1-phenyl-2-pyridin-4-ylethanone | 234766-95-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(tert-butyldimethylsilanyloxy)-1-phenyl-2-pyridin-4-ylethanone
• 英文别名: 2-(Tert-butyl-dimethyl-silanyloxy)-1-phenyl-2-pyridin-4-yl-ethanone；2-[tert-butyl(dimethyl)silyl]oxy-1-phenyl-2-pyridin-4-ylethanone
• CAS: 234766-95-1
• 化学式: C₁₉H₂₅NO₂Si
• 分子量: 327.499
• InChiKey: WWHJKRVRYOHNPF-UHFFFAOYSA-N

物化性质

• 沸点：
  416.6±35.0 °C(Predicted)
• 密度：
  1.033±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.03
• 重原子数：
  23
• 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：

  对溴苯甲醛 、 2-(tert-butyldimethylsilanyloxy)-1-phenyl-2-pyridin-4-ylethanone 在 copper diacetate 、 ammonium acetate 、 溶剂黄146 作用下， 反应 4.0h， 生成 4-[2-(4-Bromo-phenyl)-5-phenyl-3H-imidazol-4-yl]-pyridine
  参考文献：
  名称：

  Substituted Imidazoles as Glucagon Receptor Antagonists

  摘要：

  A modestly active, nonselective triarylimidazole lead was optimized for binding affinity with the human glucagon receptor. This led to the identification of a 2- and/or 4-alkyl or alkyloxy substituent on the imidazole C4-aryl group as a structural determinant for significant enhancement in binding with the glucagon receptor (e.g., 41, IC50 = 0.053 muM) and selectivity (> 1000x) over p38 MAP kinase in this class of compounds. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00498-x
• 作为产物：
  描述：

  N-甲基-N-甲基苯甲酰胺 、 4-(叔丁基二甲基甲硅烷基氧基甲基)吡啶 在 lithium diisopropyl amide 作用下， 生成 2-(tert-butyldimethylsilanyloxy)-1-phenyl-2-pyridin-4-ylethanone
  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

• Oxazole hydroxamic acid derivatives and use thereof
  申请人：SK Holdings Co., Ltd.

  公开号：US08039634B2

  公开（公告）日：2011-10-18

  Provided are an oxazole hydroxamic acid derivatives and pharmaceutically useful salt thereof as a histone deacetylase inhibitor. The oxazole hydroxamic acid derivative and pharmaceutically useful salt thereof, prepared in accordance with the present invention, can treat and/or prevent various cancers and inflammatory diseases caused by histone deacetylase.

  提供一种噁唑羟肟酸衍生物及其药用盐，作为组蛋白去乙酰化酶抑制剂。根据本发明制备的噁唑羟肟酸衍生物及其药用盐，可用于治疗和/或预防由组蛋白去乙酰化酶引起的各种癌症和炎症性疾病。
• Oxazole Hydroxamic Acid Derivatives and Use Thereof
  申请人：Cho Jeong-woo

  公开号：US20090209596A1

  公开（公告）日：2009-08-20

  Provided are an oxazole hydroxamic acid derivative and a pharmaceutically useful salt thereof as a histone deacetylase inhibitor The oxazole hydroxamic acid derivative and pharmaceutically useful salt thereof, prepared in accordance with the present invention, can treat and/or prevent various cancers and inflammatory diseases caused by histone deacetylase.

  提供了一种噁唑羟肟酸衍生物及其药用盐，作为组蛋白去乙酰化酶抑制剂。根据本发明制备的噁唑羟肟酸衍生物及其药用盐，可用于治疗和/或预防由组蛋白去乙酰化酶引起的各种癌症和炎症性疾病。
• Substituted Imidazoles as Glucagon Receptor Antagonists
  作者：Linda L. Chang、Kelly L. Sidler、Margaret A. Cascieri、Stephen de Laszlo、Greg Koch、Bing Li、Malcolm MacCoss、Nathan Mantlo、Stephen O'Keefe、Margaret Pang、Anna Rolando、William K. Hagmann

  DOI：10.1016/s0960-894x(01)00498-x

  日期：2001.9

  A modestly active, nonselective triarylimidazole lead was optimized for binding affinity with the human glucagon receptor. This led to the identification of a 2- and/or 4-alkyl or alkyloxy substituent on the imidazole C4-aryl group as a structural determinant for significant enhancement in binding with the glucagon receptor (e.g., 41, IC50 = 0.053 muM) and selectivity (> 1000x) over p38 MAP kinase in this class of compounds. (C) 2001 Elsevier Science Ltd. All rights reserved.
• 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.