5-chloro-N-(4-methylphenyl)-2-nitrobenzamide | 574008-44-9

• 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: 5-chloro-N-(4-methylphenyl)-2-nitrobenzamide
• CAS: 574008-44-9
• 化学式: C₁₄H₁₁ClN₂O₃
• 分子量: 290.706
• InChiKey: WIIVQTPZFBLHKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 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：
  3

反应信息

• 作为反应物：
  描述：

  5-chloro-N-(4-methylphenyl)-2-nitrobenzamide 在 溶剂黄146 、 三乙胺 、 tin(ll) chloride 作用下， 以 乙醇 为溶剂， 反应 8.0h， 生成 1,3-dioxo-2-(4-(piperidin-1-yl)-2-(p-tolylcarbamoyl)phenyl)isoindoline-5-carboxylic acid
  参考文献：
  名称：

  Structure–activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo

  摘要：

  The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Common. 2014, 450, 1063). Herein, we establish structure activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo. 2015 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.08.058
• 作为产物：
  描述：

  5-氯-2-硝基苯甲酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.33h， 生成 5-chloro-N-(4-methylphenyl)-2-nitrobenzamide
  参考文献：
  名称：

  Structure–activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo

  摘要：

  The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Common. 2014, 450, 1063). Herein, we establish structure activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo. 2015 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.08.058

文献信息

• Efficient and Convenient Synthesis of Pyrrolo[1,2-<i>a</i>]quinazoline Derivatives with the Aid of Tin(II) Chloride
  作者：Manman Wang、Guolan Dou、Daqing Shi

  DOI：10.1021/cc100062e

  日期：2010.7.12

  An efficient, convenient, one-pot synthesis of 2,3,3a,4-tetrahydropyrrolo[1,2-a]quinazolin-5(1H)-one and 2,3,3a,4-tetrahydropyrrolo[1,2-a]quinazoline-1,5-dione was accomplished in good yields via the novel reductive cyclization of 2-nitrobenzamides with haloketones or keto acids mediated by SnCl2·2H2O system. A variety of substrates can participate in the process with good yields, making this methodology

  2,3,3a，4-四氢吡咯并[1,2 - a ]喹唑啉-5（1 H）-one和2,3,3a，4-四氢吡咯并[1,2-通过由SnCl 2 ·2H 2 O系统介导的2-硝基苯甲酰胺与卤代酮或酮酸的新型还原性环化反应，可以成功地制得]]喹唑啉-1,5-二酮。多种底物可以高收率参与该过程，从而使该方法适用于药物发现工作中的文库合成。
• Efficient and convenient synthesis of spiroindolinone-quinazolines induced by stannous chloride
  作者：Yu Hu、Man-Man Wang、Hui Chen、Da-Qing Shi

  DOI：10.1016/j.tet.2011.09.130

  日期：2011.12

  An efficient, convenient, one-pot synthesis of 1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dione derivatives was accomplished in good yields via the novel reductive cyclization of 2-nitrobenzamides and isatins mediated by SnCl2·2H2O system. A variety of substrates can participate in the process with good yields, making this methodology have broad applicability. The structure of compound 3c has been

  一种高效，方便，单釜1的合成“ ħ -螺[二氢吲哚-3,2'-喹唑啉] -2,4-'（3' ħ） -二酮衍生物是在良好的产率通过的2新颖还原环化完成SnCl 2 ·2H 2 O系统介导的硝基硝基苯甲酰胺和靛红。多种基材可以高产率参与该工艺，从而使该方法具有广泛的适用性。化合物3c的结构已经通过X射线衍射分析确认。
• Structure–activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo
  作者：Rémi Caraballo、Mikael Larsson、Stefan K. Nilsson、Madelene Ericsson、Weixing Qian、Nam Phuong Nguyen Tran、Tomas Kindahl、Richard Svensson、Valeria Saar、Per Artursson、Gunilla Olivecrona、Per-Anders Enquist、Mikael Elofsson

  DOI：10.1016/j.ejmech.2015.08.058

  日期：2015.10

  The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Common. 2014, 450, 1063). Herein, we establish structure activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo. 2015 The Authors. Published by Elsevier Masson SAS.