3-nitro-N-(3-(trifluoromethyl)phenyl)benzamide | 180631-67-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-nitro-N-(3-(trifluoromethyl)phenyl)benzamide
• 英文别名: 3-nitro-N-(3-trifluoromethylphenyl)benzamide；3-nitro-N-[3-(trifluoromethyl)phenyl]benzamide
• CAS: 180631-67-8
• 化学式: C₁₄H₉F₃N₂O₃
• mdl: MFCD00033973
• 分子量: 310.232
• InChiKey: UJNOYTXEORQEGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-nitro-N-(3-(trifluoromethyl)phenyl)benzamide 在 tin(II) chloride dihdyrate 、 硫酸 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 2.5h， 生成 2-amino-1-(3-((3-(trifluoromethyl)phenyl)carbamoyl)phenyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carboxamide
  参考文献：
  名称：

  Pyrrolo[3,2-b]quinoxaline Derivatives as Types I_1/2 and II Eph Tyrosine Kinase Inhibitors: Structure-Based Design, Synthesis, and in Vivo Validation

  摘要：

  The X-ray crystal structures of the catalytic domain of the EphA3 tyrosine kinase in complex with two type I inhibitors previously discovered in silico (compounds A and B) were used to design type I-1/2 and II inhibitors. Chemical synthesis of about 25 derivatives culminated in the discovery of compounds 11d (type I-1/2), 7b, and 7g (both of type II), which have low-nanomolar affinity for Eph kinases in vitro and a good selectivity profile on a panel of 453 human kinases (395 nonmutant). Surface plasmon resonance measurements show a very slow unbinding rate (1/115 min) for inhibitor 7m. Slow dissociation is consistent with a type II binding mode in which the hydrophobic moiety (trifluoromethyl-benzene) of the inhibitor is deeply buried in a cavity originating from the displacement of the Phe side chain of the so-called DFG motif as observed in the crystal structure of compound 7m. The inhibitor 11d displayed good in vivo efficacy in a human breast cancer xenograft.

  DOI：

  10.1021/jm5009242
• 作为产物：
  描述：

  间氨基三氟甲苯 、 间硝基苯甲酸 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以79%的产率得到3-nitro-N-(3-(trifluoromethyl)phenyl)benzamide
  参考文献：
  名称：

  Pyrrolo[3,2-b]quinoxaline Derivatives as Types I_1/2 and II Eph Tyrosine Kinase Inhibitors: Structure-Based Design, Synthesis, and in Vivo Validation

  摘要：

  The X-ray crystal structures of the catalytic domain of the EphA3 tyrosine kinase in complex with two type I inhibitors previously discovered in silico (compounds A and B) were used to design type I-1/2 and II inhibitors. Chemical synthesis of about 25 derivatives culminated in the discovery of compounds 11d (type I-1/2), 7b, and 7g (both of type II), which have low-nanomolar affinity for Eph kinases in vitro and a good selectivity profile on a panel of 453 human kinases (395 nonmutant). Surface plasmon resonance measurements show a very slow unbinding rate (1/115 min) for inhibitor 7m. Slow dissociation is consistent with a type II binding mode in which the hydrophobic moiety (trifluoromethyl-benzene) of the inhibitor is deeply buried in a cavity originating from the displacement of the Phe side chain of the so-called DFG motif as observed in the crystal structure of compound 7m. The inhibitor 11d displayed good in vivo efficacy in a human breast cancer xenograft.

  DOI：

  10.1021/jm5009242

文献信息

• 2-Amino-1-phenyl-pyrrolo[3,2-b]quinoxaline-3-carboxamide derivates
  申请人：Universität Zürich

  公开号：EP2924039A1

  公开（公告）日：2015-09-30

  The invention relates to compound characterized by a general formula (1), wherein n of R1n is 0, 1, 2, 3 or 4, in particular n of R1n is 0 or 1, and each R1 independently from any other R1 is C1-C3 alkyl, C1-C3 haloalkyl or C1-C3 alkoxy, and DA is a Donor-Acceptor group. The invention relates further to a compound or a pharmaceutical preparation for use in a method for treatment of cancer or intraocular neovascular syndromes.

  该发明涉及一种具有一般式(1)的化合物，其中R1n的n为0、1、2、3或4，特别是R1n的n为0或1，每个R1独立于其他R1，为C1-C3烷基、C1-C3卤代烷基或C1-C3烷氧基，DA为给体-受体基团。该发明还涉及一种化合物或药物制剂，用于治疗癌症或眼内新生血管综合征的方法。
• Cyclooxygenase-1-Selective Inhibitors Are Attractive Candidates for Analgesics That Do Not Cause Gastric Damage. Design and in Vitro/in Vivo Evaluation of a Benzamide-Type Cyclooxygenase-1 Selective Inhibitor
  作者：Hiroki Kakuta、Xiaoxia Zheng、Hiroyuki Oda、Shun Harada、Yukio Sugimoto、Kenji Sasaki、Akihiro Tai

  DOI：10.1021/jm701191z

  日期：2008.4.1

  Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable to COX-1-inhibitory activity or other bioactivities. Here, we report that N-(5-amino-2-pyridinyl)-4(trifluoromethyl)benzamide (18f, TFAP), which has a structure clearly different from those of currently available COX-1-selective inhibitors, is a potent COX-1-selective inhibitor (COX-1IC(50) = 0.80 +/- 0.05 mu M, COX-2IC(50) = 210 I mu M). This compound causes little gastric damage in rats even at an oral dose of 300 mg/kg, though it has an analgesic effect at as low a dose as 10 mg/kg. Our results show that COX-1-selective inhibitors can be analgesic agents without causing gastric damage.
• [EN] 2-AMINO-1-PHENYL-PYRROLO[3,2-B]QUINOXALINE-3-CARBOXAMIDE DERIVATES<br/>[FR] DÉRIVÉS 2-AMINO-1-PHÉNYL-PYRROLO[3,2-B]QUINOXALINE-3-CARBOXAMIDE
  申请人：UNIV ZUERICH

  公开号：WO2015144926A1

  公开（公告）日：2015-10-01

  The invention relates to compound characterized by a general formula (1), wherein n of R1n is 0, 1, 2, 3 or 4, in particular n of R1n is 0 or 1, and each R1 independently from any other R1 is C1-C3 alkyl, C1-C3 haloalkyl or C1-C3 alkoxy, and DA is a Donor-Acceptor group. The invention relates further to a compound or a pharmaceutical preparation for use in a method for treatment of cancer or intraocular neovascular syndromes.
• Discovery and Identification of Small Molecules as Methuosis Inducers with <i>in Vivo</i> Antitumor Activities
  作者：Wei Huang、Xihuan Sun、Yunzhan Li、Zhixiang He、Li Li、Zhou Deng、Xiaoxing Huang、Shang Han、Ting Zhang、Jiaji Zhong、Zheng Wang、Qingyan Xu、Jianming Zhang、Xianming Deng

  DOI：10.1021/acs.jmedchem.8b00753

  日期：2018.6.28

  Methuosis is a novel nonapoptotic mode of cell death characterized by vacuole accumulation in the cytoplasm. In this article, we describe a series of azaindole-based compounds that cause vacuolization in MDA-MB-231 cells. The most potent vacuole inducer, compound 13 (compound 13), displayed differential cytotoxicities against a broad panel of cancer cell lines, such as MDA-MB-231, A375, HCT116, and MCF-7, but it did not inhibit the growth of the nontumorigenic epithelial cell line MCF-10A. A mechanism study confirmed that the cell death was caused by inducing methuosis. Furthermore, compound 13 exhibited substantial pharmacological efficacy in the suppression of tumor growth in a xenograft mouse model of MDA-MB-231 cells without apparent side effects, which makes this compound the first example of a methuosis inducer with potent in vivo efficacy. These results demonstrate that methuosis inducers might serve as novel therapeutics for the treatment of cancer.
• Pyrrolo[3,2-<i>b</i>]quinoxaline Derivatives as Types I_1/2 and II Eph Tyrosine Kinase Inhibitors: Structure-Based Design, Synthesis, and <i>in Vivo</i> Validation
  作者：Andrea Unzue、Jing Dong、Karine Lafleur、Hongtao Zhao、Emilie Frugier、Amedeo Caflisch、Cristina Nevado

  DOI：10.1021/jm5009242

  日期：2014.8.14

  The X-ray crystal structures of the catalytic domain of the EphA3 tyrosine kinase in complex with two type I inhibitors previously discovered in silico (compounds A and B) were used to design type I-1/2 and II inhibitors. Chemical synthesis of about 25 derivatives culminated in the discovery of compounds 11d (type I-1/2), 7b, and 7g (both of type II), which have low-nanomolar affinity for Eph kinases in vitro and a good selectivity profile on a panel of 453 human kinases (395 nonmutant). Surface plasmon resonance measurements show a very slow unbinding rate (1/115 min) for inhibitor 7m. Slow dissociation is consistent with a type II binding mode in which the hydrophobic moiety (trifluoromethyl-benzene) of the inhibitor is deeply buried in a cavity originating from the displacement of the Phe side chain of the so-called DFG motif as observed in the crystal structure of compound 7m. The inhibitor 11d displayed good in vivo efficacy in a human breast cancer xenograft.