1-[3-bromo-5-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole | 942077-06-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-[3-bromo-5-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole
• 英文别名: 1-[3-bromo-5-(trifluoromethyl)phenyl]-2,5-dimethylpyrrole
• CAS: 942077-06-7
• 化学式: C₁₃H₁₁BrF₃N
• mdl: MFCD21532642
• 分子量: 318.136
• InChiKey: LTVPCWSIPOVQDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  4.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[3-bromo-5-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole 在 正丁基锂 、 硫酸 、 盐酸羟胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 乙二醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 170.67h， 生成
  参考文献：
  名称：

  Design and Optimization of Potent and Orally Bioavailable Tetrahydronaphthalene Raf Inhibitors

  摘要：

  Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.

  DOI：

  10.1021/jm101479y
• 作为产物：
  描述：

  2,5-己二酮 、 3-氨基-5-溴三氟甲苯 在 对甲苯磺酸一水合物 作用下， 以 甲苯 为溶剂， 反应 1.0h， 以to give 1-[3-bromo-5-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole (18.15 g, 98%) as orange oil的产率得到1-[3-bromo-5-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole
  参考文献：
  名称：

  Bicyclic compounds with kinase inhibitory activity

  摘要：

  本发明提供了一种新颖的双环化合物，可用作蛋白激酶抑制剂。本发明还提供了包括本发明化合物的制药组合物以及使用该组合物治疗各种疾病的方法。

  公开号：

  US20070149533A1

文献信息

• Bicyclic compounds with kinase inhibitory activity
  申请人：Calderwood F. Emily

  公开号：US20070149533A1

  公开（公告）日：2007-06-28

  The present invention provides novel bicyclic compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

  本发明提供了一种新颖的双环化合物，可用作蛋白激酶抑制剂。本发明还提供了包括本发明化合物的制药组合物以及使用该组合物治疗各种疾病的方法。
• US8110687B2
  申请人：——

  公开号：US8110687B2

  公开（公告）日：2012-02-07
• [EN] BICYCLIC COMPOUNDS WITH KINASE INHIBITORY ACTIVITY<br/>[FR] COMPOSES BICYCLIQUES AYANT UNE ACTIVITE INHIBITRICE DE KINASE
  申请人：MILLENNIUM PHARM INC

  公开号：WO2007067444A1

  公开（公告）日：2007-06-14

  [EN] The present invention provides novel bicyclic compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.
  [FR] La présente invention concerne de nouveaux composés bicycliques utiles en tant qu'inhibiteurs de protéine kinases. L'invention concerne en outre des compositions pharmaceutiques comprenant les composés de l'invention et des procédés d'utilisation des compositions dans le traitement de différentes maladies.
• Design and Optimization of Potent and Orally Bioavailable Tetrahydronaphthalene Raf Inhibitors
  作者：Alexandra E. Gould、Ruth Adams、Sharmila Adhikari、Kathleen Aertgeerts、Roushan Afroze、Christopher Blackburn、Emily F. Calderwood、Ryan Chau、Jouhara Chouitar、Matthew O. Duffey、Dylan B. England、Cheryl Farrer、Nancy Forsyth、Khristofer Garcia、Jeffery Gaulin、Paul D. Greenspan、Ribo Guo、Sean J. Harrison、Shih-Chung Huang、Natalia Iartchouk、Dave Janowick、Mi-Sook Kim、Bheemashankar Kulkarni、Steven P. Langston、Jane X. Liu、Li-Ting Ma、Saurabh Menon、Hirotake Mizutani、Erin Paske、Christelle C. Renou、Mansoureh Rezaei、R. Scott Rowland、Michael D. Sintchak、Michael D. Smith、Stephen G. Stroud、Ming Tregay、Yuan Tian、Ole P. Veiby、Tricia J. Vos、Stepan Vyskocil、Juliet Williams、Tianlin Xu、Johnny J. Yang、Jason Yano、Hongbo Zeng、Dong Mei Zhang、Qin Zhang、Katherine M. Galvin

  DOI：10.1021/jm101479y

  日期：2011.3.24

  Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.