4-[(3,4,5-trimethoxybenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-carboxamide

• 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-[(3,4,5-trimethoxybenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-carboxamide
• 英文别名: 1-methyl-3-propyl-4-(3,4,5-trimethoxybenzamido)-1H-pyrazole-5-carboxamide；2-Methyl-5-propyl-4-[(3,4,5-trimethoxybenzoyl)amino]pyrazole-3-carboxamide
• 化学式: C₁₈H₂₄N₄O₅
• 分子量: 376.412
• InChiKey: YIUJSTZMOXFARH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-[(3,4,5-trimethoxybenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-carboxamide 在 aluminum oxide 作用下， 反应 0.02h， 以98%的产率得到5-(3,4,5-trimethoxyphenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
  参考文献：
  名称：

  修饰，经济有效地合成可变取代的吡唑并[4,3- d ]嘧啶-7-酮

  摘要：

  1-甲基-3-丙基-1 H-吡唑-5-羧酸（3）在黑暗中仅在4位被溴溴化。然后通过依次用亚硫酰氯和氢氧化铵处理，将溴化产物8转化为1-甲基-3-丙基-1 H-吡唑-5-羧酰胺9。在微波（MW）照射下，用各种芳基酰胺处理羧酰胺9，得到4-芳酰基氨基-1-甲基-3-丙基-1 H-吡唑-5-羧酰胺10-22和5-芳基-1-甲基-3-丙基-1,6-二氢-1 H-吡唑并[4,3 - d ]嘧啶-7-酮23-35。1小时通过常规加热或通过MW辐射，也将-吡唑-5-羧酰胺10-22转化为嘧啶酮23-35。但是，MW辐照法可在很短的时间内提供极好的收率。

  DOI：

  10.1002/jhet.5570420608
• 作为产物：
  描述：

  1-methyl-4-nitro-3-propyl-1H-pyrazole-5-carbonyl chloride 在 ammonium hydroxide 、 tin(II) chloride dihdyrate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 4-[(3,4,5-trimethoxybenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  Novel pyrazole-5-carboxamide and pyrazole–pyrimidine derivatives: Synthesis and anticancer activity

  摘要：

  A series of novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives were designed and synthesized. All compounds have been screened for their antiproliferative activity against MGC-803, SGC-7901 and Bcap-37 cell lines in vitro. The results revealed that compounds 8a, 8c and 8e exhibited strong inhibitory activity against MGC-803 cell line. The flow cytometric analysis result showed that compound 8e could inhibit MGC-803 proliferation. Some title compounds were tested against telomerase, and compound 8e showed the most potent inhibitory activity with IC50 value at 1.02 +/- 0.08 mu M. The docking simulation of compound 8e was performed to get the probable binding model, among them, LYS 189, LYS 372, LYS 249 and ASP 254 may be the key residues for the telomerase activity. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.013

文献信息

• Design and synthesis of novel pyrazolo[4,3-<i>d</i>]pyrimidines as potential therapeutic agents for acute lung injury
  作者：Bao Shi Wang、Xin Huang、Liu Zeng Chen、Ming Ming Liu、Jing Bo Shi

  DOI：10.1080/14756366.2019.1618291

  日期：2019.1.1

  Abstract Four series of total 35 new pyrazolo[4,3-d]pyrimidine compounds were designed, synthesized and evaluated for their inhibitory activity against LPS-induced NO production in RAW264.7 macrophages. Among them, compound 4e was found to be the most potent inhibitor, which decreased the production of cytokines in vitro, such as NO, IL-6 and TNF-α, with IC50 values of 2.64, 4.38 and 5.63 μM, respectively

  抽象的 设计，合成并评估了总共35种新的吡唑并[4,3- d ]嘧啶化合物的四个系列，它们对RAW264.7巨噬细胞中LPS诱导的NO产生的抑制活性。其中，化合物4e被认为是最有效的抑制剂，可降低体外细胞因子的生成，例如NO，IL-6和TNF-α，IC 50值分别为2.64、4.38和5.63μM。进一步的研究表明，化合物4e通过抑制TLR4 / p38信号通路抑制巨噬细胞的细胞因子分泌。此外，化合物4e在体内显示LPS诱导的急性肺损伤模型中的抗炎活性。这些数据表明，化合物4e可能是用于治疗ALI的有前途的先导结构。
• 一种嘧啶并吡唑杂环化合物、制备方法、用途
  申请人：安徽医科大学

  公开号：CN108178760B

  公开（公告）日：2020-02-18

  本发明公开了一种如结构通式I的所示的嘧啶并吡唑杂环化合物、制备方法、用途。本发明的吡唑并嘧啶骨架及其生物电子等排体为杂环类化合物，整体制备方法简单，能够快速制得吡唑并嘧啶的化合物。
• A modified, economical and efficient synthesis of variably substituted pyrazolo[4,3-<i>d</i>]pyrimidin-7-ones
  作者：Khalid Mohammed Khan、Ghulam Murtaza Maharvi、Muhammad Iqbal Choudhary、Atta-ur- Rahman、Shahnaz Perveen

  DOI：10.1002/jhet.5570420608

  日期：2005.9

  treated with various aroyl amides under microwave (MW) irradiation to afford 4-aroylamino-1-methyl-3-propyl-1H-pyrazole-5-carboxamides 10-22 and 5-aryl-1-methyl-3-propyl-1,6-dihydro-1H-pyrazolo[4,3-d]pyrimidin-7-ones 23-35. The 1H-pyrazole-5-carboxamides 10-22 were also converted to pyrimidinones 23-35 either by conventional heating or by MW irradiation. However, MW irradiation method gives excellent yields

  1-甲基-3-丙基-1 H-吡唑-5-羧酸（3）在黑暗中仅在4位被溴溴化。然后通过依次用亚硫酰氯和氢氧化铵处理，将溴化产物8转化为1-甲基-3-丙基-1 H-吡唑-5-羧酰胺9。在微波（MW）照射下，用各种芳基酰胺处理羧酰胺9，得到4-芳酰基氨基-1-甲基-3-丙基-1 H-吡唑-5-羧酰胺10-22和5-芳基-1-甲基-3-丙基-1,6-二氢-1 H-吡唑并[4,3 - d ]嘧啶-7-酮23-35。1小时通过常规加热或通过MW辐射，也将-吡唑-5-羧酰胺10-22转化为嘧啶酮23-35。但是，MW辐照法可在很短的时间内提供极好的收率。
• Novel Pyrazolo[4,3-<i>d</i>]pyrimidine as Potent and Orally Active Inducible Nitric Oxide Synthase (iNOS) Dimerization Inhibitor with Efficacy in Rheumatoid Arthritis Mouse Model
  作者：Jing Bo Shi、Liu Zeng Chen、Bao Shi Wang、Xin Huang、Ming Ming Jiao、Ming Ming Liu、Wen Jian Tang、Xin Hua Liu

  DOI：10.1021/acs.jmedchem.9b00039

  日期：2019.4.25

  structure-activity relationships, four series (A-D) of total 90 new pyrazolo[4,3- d]pyrimidine compounds were designed and synthesized. All the compounds have been tested for their anti-inflammatory activities by inhibiting of LPS-induced NO production. A clear structure-activity relationship has been concluded step by step, and finally 3,4,5-trimethoxystyryl-1 H-pyrazolo[4,3- d]pyrimidine was found to be the most

  为了发现治疗关节炎的新型抗炎药，并基于初步的构效关系，设计并合成了总共90种新的吡唑并[4,3-d]嘧啶化合物的四个系列（AD）。已通过抑制LPS诱导的NO生成来测试所有化合物的抗炎活性。逐步得出明确的结构-活性关系，最后发现3,4,5-三甲氧基苯乙烯-1 H-吡唑并[4,3-d]嘧啶是活性最高的支架。其中，化合物D27被发现是最有效的抗炎药（IC50 = 3.17μM），具有低毒性和对NO释放的强烈抑制作用（10μM时IR = 90.4％）。该化合物还显示出对iNOS的有效抑制，IC50值为1.12μM。初步的机理研究表明，它可能会干扰活性二聚iNOS的稳定性和形成。该化合物的抗炎作用由佐剂诱发的关节炎在大鼠模型中确定。我们相信这些发现将进一步支持将来对更有效的iNOS抑制剂进行合理设计的研究。
• Novel pyrazole-5-carboxamide and pyrazole–pyrimidine derivatives: Synthesis and anticancer activity
  作者：Jing Bo Shi、Wen Jian Tang、Xing Bao qi、Rong Li、Xin Hua Liu

  DOI：10.1016/j.ejmech.2014.12.013

  日期：2015.1

  A series of novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives were designed and synthesized. All compounds have been screened for their antiproliferative activity against MGC-803, SGC-7901 and Bcap-37 cell lines in vitro. The results revealed that compounds 8a, 8c and 8e exhibited strong inhibitory activity against MGC-803 cell line. The flow cytometric analysis result showed that compound 8e could inhibit MGC-803 proliferation. Some title compounds were tested against telomerase, and compound 8e showed the most potent inhibitory activity with IC50 value at 1.02 +/- 0.08 mu M. The docking simulation of compound 8e was performed to get the probable binding model, among them, LYS 189, LYS 372, LYS 249 and ASP 254 may be the key residues for the telomerase activity. (C) 2014 Elsevier Masson SAS. All rights reserved.