4-氯-5-乙基-吡咯并[2,1-f][1,2,4]三嗪-6-羧酸乙酯 | 310442-94-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并三嗪类
• 中文名称: 4-氯-5-乙基-吡咯并[2,1-f][1,2,4]三嗪-6-羧酸乙酯
• 中文别名: 4-氯-5-乙基吡咯并[2,1-f][1,2,4]三嗪-6-羧酸乙酯
• 英文名称: ethyl 4-chloro-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate
• 英文别名: 4-Chloro-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic Acid Ethyl Ester
• CAS: 310442-94-5
• 化学式: C₁₁H₁₂ClN₃O₂
• 分子量: 253.688
• InChiKey: QJCOYJRUMINHLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-氯-5-乙基-吡咯并[2,1-f][1,2,4]三嗪-6-羧酸乙酯 在 氯化亚砜 、 二异丁基氢化铝 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 [4-(1-Benzyl-1H-indazol-5-ylamino)-5-ethyl-pyrrolo[2,1-f][1,2,4]triazin-6-yl]-acetonitrile
  参考文献：
  名称：

  New dual inhibitors of EGFR and HER2 protein tyrosine kinases

  摘要：

  A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. A general route toward their synthesis, which enables functionalization at multiple sites, has been developed. Biological evaluation in enzymatic and cell-based assays has identified a series of C-6 carbamates with potent biochemical and cellular activities.

  DOI：

  10.1016/j.bmcl.2005.07.027
• 作为产物：
  描述：

  2,4-二乙基-3-乙基-1H-吡咯-2,4-二羧酸酯 在 二苯基膦酰羟胺 、 sodium hydride 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-氯-5-乙基-吡咯并[2,1-f][1,2,4]三嗪-6-羧酸乙酯
  参考文献：
  名称：

  New dual inhibitors of EGFR and HER2 protein tyrosine kinases

  摘要：

  A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. A general route toward their synthesis, which enables functionalization at multiple sites, has been developed. Biological evaluation in enzymatic and cell-based assays has identified a series of C-6 carbamates with potent biochemical and cellular activities.

  DOI：

  10.1016/j.bmcl.2005.07.027

文献信息

• Pyrrolotriazine inhibitors of kinases
  申请人：Bristol Myers Squibb Company

  公开号：US06982265B1

  公开（公告）日：2006-01-03

  The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit the tyrosine kinase activity of growth factor receptors such as VEGFR-2, FGFR-1, PDGFR, HER-1, HER-2, thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.

  本发明提供了公式I的化合物及其药用可接受的盐。公式I的化合物抑制了诸如VEGFR-2、FGFR-1、PDGFR、HER-1、HER-2等生长因子受体的酪氨酸激酶活性，从而使其作为抗肿瘤剂具有用途。公式I的化合物也用于治疗通过生长因子受体运作的信号转导通路相关的其他疾病。
• Design, Synthesis, and Anti-inflammatory Properties of Orally Active 4-(Phenylamino)-pyrrolo[2,1-<i>f</i>][1,2,4]triazine p38α Mitogen-Activated Protein Kinase Inhibitors
  作者：John Hynes、Alaric J. Dyckman、Shuqun Lin、Stephen T. Wrobleski、Hong Wu、Kathleen M. Gillooly、Steven B. Kanner、Herinder Lonial、Derek Loo、Kim W. McIntyre、Sidney Pitt、Ding Ren Shen、David J. Shuster、XiaoXia Yang、Rosemary Zhang、Kamelia Behnia、Hongjian Zhang、Punit H. Marathe、Arthur M. Doweyko、John S. Tokarski、John S. Sack、Matthew Pokross、Susan E. Kiefer、John A. Newitt、Joel C. Barrish、John Dodd、Gary L. Schieven、Katerina Leftheris

  DOI：10.1021/jm7009414

  日期：2008.1.1

  A novel structural class of p38 mitogen-activated protein (MAP) kinase inhibitors consisting of substituted 4-(phenylamino)-pyrrolo[2,1- f][1,2,4]triazines has been discovered. An initial subdeck screen revealed that the oxindole-pyrrolo[2,1- f][1,2,4]triazine lead 2a displayed potent enzyme inhibition (IC 50 60 nM) and was active in a cell-based TNFalpha biosynthesis inhibition assay (IC 50 210 nM). Replacement of the C4 oxindole with 2-methyl-5- N-methoxybenzamide aniline 9 gave a compound with superior p38 kinase inhibition (IC 50 10 nM) and moderately improved functional inhibition in THP-1 cells. Further replacement of the C6 ester of the pyrrolo[2,1- f][1,2,4]triazine with amides afforded compounds with increased potency, excellent oral bioavailability, and robust efficacy in a murine model of acute inflammation (murine LPS-TNFalpha). In rodent disease models of chronic inflammation, multiple compounds demonstrated significant inhibition of disease progression leading to the advancement of 2 compounds 11b and 11j into further preclinical and toxicological studies.
• Discovery and Preclinical Studies of (<i>R</i>)-1-(4-(4-Fluoro-2-methyl-1<i>H</i>-indol-5-yloxy)-5- methylpyrrolo[2,1-<i>f</i>][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an In Vivo Active Potent VEGFR-2 Inhibitor
  作者：Rajeev S. Bhide、Zhen-Wei Cai、Yong-Zheng Zhang、Ligang Qian、Donna Wei、Stephanie Barbosa、Louis J. Lombardo、Robert M. Borzilleri、Xiaoping Zheng、Laurence I. Wu、Joel C. Barrish、Soong-Hoon Kim、Kenneth Leavitt、Arvind Mathur、Leslie Leith、Sam Chao、Barri Wautlet、Steven Mortillo、Robert Jeyaseelan、Daniel Kukral、John T. Hunt、Amrita Kamath、Aberra Fura、Viral Vyas、Punit Marathe、Celia D'Arienzo、George Derbin、Joseph Fargnoli

  DOI：10.1021/jm051106d

  日期：2006.4.1

  A series of substituted 4-(4-fluoro-1H-indol-5-yloxy)pyrrolo-[2,1-f][1,2,4]triazine-based inhibitors of vascular endothelial growth factor receptor-2 kinase is reported. Structure-activity relationship studies revealed that a methyl group at the 5-position and a Substituted alkoxy group at the 6-position of the pyrrolo[2, 1-f][ 1,2,4]triazine core gave potent compounds. Biochemical potency, kinase selectivity, and pharmacokinetics of the series were optimized and in vitro safety liabilities were minimized to afford BMS-540215 (12). which demonstrated robust preclinical in vivo activity in human tumor xenograft models. The L-alanine prodrug of 12, BMS-582664 (21), is currently under evaluation in clinical trials for the treatment of solid tumors.
• PYRROLOTRIAZINE INHIBITORS OF KINASES
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1183033A1

  公开（公告）日：2002-03-06
• EP1183033A4
  申请人：——

  公开号：EP1183033A4

  公开（公告）日：2002-07-17