4-chloro-N-(4-methylphenyl)-2-nitrobenzamide

• 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: 4-chloro-N-(4-methylphenyl)-2-nitrobenzamide
• 化学式: C₁₄H₁₁ClN₂O₃
• mdl: MFCD01215381
• 分子量: 290.706
• InChiKey: TXPPWEVTRFRCJR-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：

  4-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-(5-(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：

  4-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 4-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

• An efficient synthesis of quinazoline derivatives with the aid of low-valent titanium reagent
  作者：Daqing Shi、Chunling Shi、Juxian Wang、Liangce Rong、Qiya Zhuang、Xiangshan Wang

  DOI：10.1002/jhet.5570420201

  日期：2005.3

  Quinazolin-4(3H)-ones, 1,2-dihydroquinazolin-4(3H)-ones, 3,4-dihydroquinazolines, imidazo[1,2-c]-quinazolines and 5,6-dihydroimidazo[1,2-c]quinazolines were synthesized by the novel reductive reaction of nitro group, N-H bond and ortho-ester, aldehydes or ketones promoted by the low-valent titanium reagent (TiCl4-Zn system). The structures of these compounds were characterized by elemental analysis

  喹唑啉-4（3 H）-one，1,2-二氢喹唑啉-4（3 H）-one，3,4-二氢喹唑啉，咪唑并[1,2- c ]-喹唑啉和5,6-二氢咪唑并[1,2 - c ^ ]喹唑啉通过将低价钛试剂（促进的TiCl硝基，NH键和原酸酯，醛或酮的新型还原反应，合成4 -Zn系统）。这些化合物的结构通过元素分析，IR和1 HNMR光谱进行表征，并通过单晶X射线衍射分析进一步证实。
• A Novel and Efficient Synthesis of 1-Hydroxyquinazolin-4-ones via Tin(II) Chloride Induced Cyclization of 2-Nitrobenzamides and Ketones
  作者：Daqing Shi、Guolan Dou、Yao Zhou

  DOI：10.1055/s-2008-1067126

  日期：——

  A mild, efficient and novel synthesis of 2,3-dihydro-1-hydroxyquinazolin-4(1H)-ones via cyclization of 2-nitrobenz­amides and ketones induced by tin(II) chloride dihydrate is described. This new method has the advantages of accessible starting materials, convenient manipulation, short reaction times, and high yields.

  本文描述了一种温和、高效且新颖的合成2,3-二氢-1-羟基喹唑啉-4(1H)-酮的方法，该方法通过氯化亚锡（二水合物）诱导2-硝基苯胺和酮的环化反应。这种新方法具有起始材料易得、操作便利、反应时间短和产率高的优点。
• Synthesis of quinazolin-4(3 H )-ones and 1,2-dihydroquinazolin-4(3 H )-ones with the aid of a low-valent titanium reagent
  作者：Daqing Shi、Liangce Rong、Juxian Wang、Qiya Zhuang、Xiangshan Wang、Hongwen Hu

  DOI：10.1016/s0040-4039(03)00449-0

  日期：2003.4

  A short and facile synthesis of a series of quinazolin-4(3H)-ones and 1,2-dihydroquinazolin-4(3H)-ones was accomplished in good yields via the novel reductive cyclization of o-nitrobenzamides and triethyl orthoformate, aldehydes or ketones promoted by TiCl4/Zn.

  一系列喹唑啉-4-的短而简便合成（3 ħ） -酮和1,2-二氢喹唑啉-4（3 H ^） -酮在良好的产率通过的新颖还原性环化完成ö -nitrobenzamides和原甲酸三乙酯， TiCl 4 / Zn促进的醛或酮。
• Facile Synthesis of Substituted Quinazolin‐4‐(3H)‐ones Using Low‐Valence Titanium Reagent
  作者：Daqing Shi、Liangce Rong、Juxian Wang、Qiya Zhuang、Xiangshan Wang、Hongwen Hu

  DOI：10.1081/scc-120034156

  日期：2004.12.31

  Abstract A short and facile synthesis of a series of 3‐aryl quinazolin‐4‐(3H)‐ones was accomplished in good yields via the intermolecular reductive coupling reaction of N‐aryl‐2‐nitrobenzamide and triethyl orthoformate promoted by TiCl4/Zn.

  摘要 通过 TiCl4/Zn 促进的 N-芳基-2-硝基苯甲酰胺和原甲酸三乙酯的分子间还原偶联反应，以良好的收率快速简便地合成了一系列 3-芳基喹唑啉-4-(3H)-酮。
• Shi, Daqing; Rong, Liangce; Wang, Juxian, Journal of Chemical Research - Part S, 2003, # 6, p. 366 - 367
  作者：Shi, Daqing、Rong, Liangce、Wang, Juxian、Zhuang, Qiya、Hu, Hongwen

  DOI：——

  日期：——