2-[(二甲基氨基)亚甲基]-3-(4-溴苯基)-3-氧代丙腈 | 52200-18-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-[(二甲基氨基)亚甲基]-3-(4-溴苯基)-3-氧代丙腈
• 英文名称: 2-(4-bromobenzoyl)-3-dimethylaminoacrylonitrile
• 英文别名: 2-(4-Bromobenzoyl)-3-(dimethylamino)prop-2-enenitrile
• CAS: 52200-18-7
• 化学式: C₁₂H₁₁BrN₂O
• 分子量: 279.136
• InChiKey: HFPTXOGUUFRBIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2926909090

反应信息

• 作为反应物：
  描述：

  2-[(二甲基氨基)亚甲基]-3-(4-溴苯基)-3-氧代丙腈 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以77%的产率得到3-(4-bromophenyl)-1H-pyrazole-4-carbonitrile
  参考文献：
  名称：

  Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds

  摘要：

  V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing a phenylpyrazole group (dimethyl-[2-(4-{5-[4-(1H-pyrazol-3-yl)-phenyl]-4-pyridin- 4-yl-1H-imidazol-2-yl}-phenoxy)-ethyl]-amine, 1a) was identified as an active BRAF inhibitor. Based on this starting point, we synthesized a series of analogues leading to the discovery of 6-{2-[4-(4-methylpiperazin- 1-yl)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-2,4-dihydro-indeno[1,2-c]pyrazole (1j), with nanomolar activity in three assays: inhibition of purified mutant BRAF activity in vitro; inhibition of oncogenic BRAF-driven extracellular regulated kinase (ERK) activation in BRAF mutant melanoma cell lines; and inhibition of proliferation in these cells. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.031
• 作为产物：
  描述：

  N,N-二甲基甲酰胺二乙基缩醛 、 4-溴苯甲酰乙腈 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-[(二甲基氨基)亚甲基]-3-(4-溴苯基)-3-氧代丙腈
  参考文献：
  名称：

  4-Aryl-5-cyano-2-aminopyrimidines as VEGF-R2 inhibitors: Synthesis and biological evaluation

  摘要：

  A novel series of 4-aryl-5-cyano-2-aminopyrimidines were synthesized and found to have potent VEGF-R2 kinase inhibitory activity. Structure-activity relationships were investigated and compound 14a was shown to be efficacious in a mouse model of corneal neovascularization. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.021

文献信息

• SYNTHESIS OF 4-CYANO- AND 5-AMINOPYRAZOLES AND DEAMINATION OF 5-AMINOPYRAZOLES
  作者：R. B. Toche、M. A. Kazi、M. N. Jachak

  DOI：10.1080/00304940809458119

  日期：2008.12

  with fumaronitrile. Junek and co-workers5 reported the synthesis of 4-cyanopyrazoles from cyanoacetaldehyde. Previous syntheses involve refluxing 3-dimethylamino-2benzoylpropenenitrile (2a) with phenylhydrazine or hydrazine in ethanol. However, the products were always a mixture of 4-cyanoand 5-aminopyrazole derivatives, which had to be separated by column chromatography> We now report a new chemoselective

  1,3,4-三取代吡唑是制备15-二苯基吡唑非核苷衍生物的重要化合物，用作HIV1非核苷逆转录酶抑制剂。4-氰基吡唑在抑制乙醇脱氢酶方面显示出显着的生物活性？这些化合物在对动物给药时也会产生骨骼肌松弛吗？Hasseneen 和同事 4 通过腈亚胺与富马腈的反应制备了这些化合物。Junek 和同事 5 报道了从氰基乙醛合成 4-氰基吡唑。先前的合成包括在乙醇中将 3-二甲氨基-2苯甲酰基丙烯腈 (2a) 与苯肼或肼回流。然而，产物始终是4-氰基和5-氨基吡唑衍生物的混合物，必须通过柱层析进行分离> 我们现在报告了一种新的化学选择性方法来合成 4-氰基或 5-氨基吡唑。3-二甲氨基-2-苯甲酰基丙烯腈 (1) 和肼 (2) 在乙醇中在催化量的盐酸存在下回流，以 60-70% 的产率提供 4-氰基吡唑 (3) 作为唯一产物；未检测到 5-氨基吡唑。3 的结构是通过分析和光谱方法建立的（方案 I）。红外光谱通常显示不同
• Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds
  作者：Dan Niculescu-Duvaz、Ion Niculescu-Duvaz、Bart M.J.M. Suijkerbuijk、Delphine Ménard、Alfonso Zambon、Arnaud Nourry、Lawrence Davies、Helen A. Manne、Frank Friedlos、Lesley Ogilvie、Douglas Hedley、Andrew K. Takle、David M. Wilson、Jean-Francois Pons、Tom Coulter、Ruth Kirk、Neus Cantarino、Steven Whittaker、Richard Marais、Caroline J. Springer

  DOI：10.1016/j.bmc.2010.06.031

  日期：2010.9

  V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing a phenylpyrazole group (dimethyl-[2-(4-5-[4-(1H-pyrazol-3-yl)-phenyl]-4-pyridin- 4-yl-1H-imidazol-2-yl}-phenoxy)-ethyl]-amine, 1a) was identified as an active BRAF inhibitor. Based on this starting point, we synthesized a series of analogues leading to the discovery of 6-2-[4-(4-methylpiperazin- 1-yl)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-2,4-dihydro-indeno[1,2-c]pyrazole (1j), with nanomolar activity in three assays: inhibition of purified mutant BRAF activity in vitro; inhibition of oncogenic BRAF-driven extracellular regulated kinase (ERK) activation in BRAF mutant melanoma cell lines; and inhibition of proliferation in these cells. (C) 2010 Elsevier Ltd. All rights reserved.
• 4-Aryl-5-cyano-2-aminopyrimidines as VEGF-R2 inhibitors: Synthesis and biological evaluation
  作者：Terry V. Hughes、Stuart L. Emanuel、Amanda K. Beck、Steven K. Wetter、Peter J. Connolly、Prabha Karnachi、Michael Reuman、Jabed Seraj、Angel R. Fuentes-Pesquera、Robert H. Gruninger、Steven A. Middleton、Ronghui Lin、Jeremy M. Davis、David F.C. Moffat

  DOI：10.1016/j.bmcl.2007.04.021

  日期：2007.6

  A novel series of 4-aryl-5-cyano-2-aminopyrimidines were synthesized and found to have potent VEGF-R2 kinase inhibitory activity. Structure-activity relationships were investigated and compound 14a was shown to be efficacious in a mouse model of corneal neovascularization. (c) 2007 Elsevier Ltd. All rights reserved.