ethyl 4-acetyl-5-methyl-1-(p-tolyl)-1H-pyrazole-3-carboxylate | 63514-80-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 4-acetyl-5-methyl-1-(p-tolyl)-1H-pyrazole-3-carboxylate
• 英文别名: ethyl 4-acetyl-5-methyl-1-(4-methylphenyl)-1H-pyrazole-3-carboxylate；ethyl 4-acetyl-5-methyl-1-(4-methylphenyl)pyrazole-3-carboxylate
• CAS: 63514-80-7
• 化学式: C₁₆H₁₈N₂O₃
• mdl: MFCD05881505
• 分子量: 286.331
• InChiKey: OPUNGNIGZSJGIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  61.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-acetyl-5-methyl-1-(p-tolyl)-1H-pyrazole-3-carboxylate 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 6.0h， 生成 ethyl 4-(1-(2-(5-((4-methoxyphenyl)diazenyl)-4-methylthiazol-2-yl)hydrazono)ethyl)-5-methyl-1-(ptolyl)-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  一些新型噻唑、1,3,4-噻二唑和吡啶并[2,3-d][1,2,4]三唑并[4,3-a]嘧啶衍生物的合成及抗菌评价

  摘要：

  New series of novel functionalized thiazoles, 1,3,4-thiadiazoles and pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines containing pyrazole moiety were synthesized using 4-acetylpyrazole as a precursor. The structures of the compounds prepared were confirmed by both spectral and elemental analyses and by alternative synthetic routes. The mechanisms of the studied reactions were also discussed. Sixteen compounds were evaluated for their in vitro antimicrobial activity. The results proclaimed that some of the tested compounds exhibited moderate to significant antibacterial and antifungal activities. Compounds lie, 11a, and lid exhibited high antibacterial activity against Bacillus subtilis compared with reference drug (Ampicillin) while compounds 11a, 6g, 18e, 18a, 11d, 6a, 11c, lib and 6d exhibited higher antifungal activity against Syncephalastrum racemosum than reference drug (Amphotericin B).

  DOI：

  10.3987/com-15-13319
• 作为产物：
  描述：

  乙烷,三氯氟- 在 盐酸 、 sodium ethanolate 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 20.0h， 生成 ethyl 4-acetyl-5-methyl-1-(p-tolyl)-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  结肠癌细胞中疏水标记诱导的 PDEδ 降解

  摘要：

  KRAS-PDEδ 蛋白质-蛋白质相互作用 (PPI) 抑制剂的开发通常受到有限的抗肿瘤活性的阻碍。在此，设计了第一个基于疏水标记 (HyT) 的 PDEδ 降解剂。化合物17c有效结合 PDEδ 并诱导 SW480 结肠癌细胞中的 PDEδ 降解。与 PDEδ 抑制剂 deltazinone 相比，基于 HyT 的降解剂17c对 KRAS 突变癌细胞表现出更高的抗肿瘤活性。这项研究强调了 HyT 作为致瘤性 PDEδ 敲低的有价值的化学工具的潜力，它可以发展成为一种有前途的抗肿瘤药物发现策略。

  DOI：

  10.1021/acsmedchemlett.1c00670

文献信息

• Pyridazinones for the treatment of cancer
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2955182A1

  公开（公告）日：2015-12-16

  The present invention relates to novel substituted pyrrolo- and pyrazolopyridazinones, as well as pharmaceutical compositions containing at least one of these substituted pyrrolo- and pyrazolo- pyridazinones together with at least one pharmaceutically acceptable carrier, excipient and/or diluent. Said novel substituted pyrrolo- and pyrazolo- pyridazinones are binding to the prenyl binding pocket of PDEδ and therefore, are useful for the prophylaxis and treatment of cancer by inhibition of the binding of PDEδ to K-Ras and of Ras signaling in cells.

  本发明涉及新型取代吡咯并吡唑吡啶酮，以及含有至少一种这些新型取代吡咯并吡唑吡啶酮的药物组合物，该药物组合物还包括至少一种药用可接受的载体、赋形剂和/或稀释剂。所述新型取代吡咯并吡唑吡啶酮结合到PDEδ的藤黄素结合口袋，因此，通过抑制PDEδ与K-Ras的结合以及细胞中Ras信号传导的结合，对癌症的预防和治疗具有用处。
• Development of Pyridazinone Chemotypes Targeting the PDEδ Prenyl Binding Site
  作者：Sandip Murarka、Pablo Martín-Gago、Carsten Schultz-Fademrecht、Alaa Al Saabi、Matthias Baumann、Eyad K. Fansa、Shehab Ismail、Peter Nussbaumer、Alfred Wittinghofer、Herbert Waldmann

  DOI：10.1002/chem.201603222

  日期：2017.5.2

  The K‐Ras GTPase is a major target in anticancer drug discovery. However, direct interference with signaling by K‐Ras has not led to clinically useful drugs yet. Correct localization and signaling by farnesylated K‐Ras is regulated by the prenyl binding protein PDEδ. Interfering with binding of PDEδ to K‐Ras by means of small molecules provides a novel opportunity to suppress oncogenic signaling. Here

  K‐Ras GTPase是抗癌药物发现的主要目标。但是，对K‐Ras信号转导的直接干扰尚未导致临床上有用的药物。异戊二烯结合蛋白PDEδ调节法尼基化的K-Ras的正确定位和信号传导。通过小分子干扰PDEδ与K-Ras的结合提供了抑制致癌信号的新机会。在这里，我们介绍了基于吡咯并吡啶并酮和吡唑并并吡并并酮以低纳摩尔亲和力与PDEδ的法呢基结合袋结合的新型K-Ras-PDEδ抑制剂化学型的鉴定和结构导向的发展。我们描述了基于吡唑并吡啶并嗪酮的K-Ras-PDEδ抑制剂的结构-性质关系以及体内药代动力学（PK）和毒物动力学（Tox）研究。
• Convenient and Efficient Method for Synthesis of Bis-Hetaryl Ketones and Evaluation of Their Antimicrobial Activity
  作者：Abdou O. Abdelhamid、Sobhi M. Gomha、Waleed A. M. A. El-Enany

  DOI：10.1002/jhet.3415

  日期：2019.2

  Sodium 1‐aryl‐3‐(3‐(ethoxycarbonyl)‐5‐methyl‐1H‐pyrazol‐4‐yl)‐3‐oxoprop‐1‐en‐1‐olate was used as precursor for the preparation of some novel derivatives of various fused azolotriazine ring systems via coupling reactions with hetaryldiazonium salts. Hydrazinolysis of the latter products yielded the corresponding pyrazolopyridazine derivatives. The structures of the products were established by their

  1-芳基-3-（3-（乙氧基羰基）-5-甲基-1 H-吡唑-4-基）-3-氧代丙-1-烯-1-油酸钠被用作制备某些新型衍生物的前体通过与杂芳基重氮盐的偶联反应制备各种稠合的三唑三嗪环系统。后一种产物的水合肼解反应产生相应的吡唑并哒嗪衍生物。产品的结构是通过其光谱数据和元素分析确定的。还评估了一些新产品的抗菌和抗真菌活性。
• In Situ Generation of Nitrilimines from Aryldiazonium Salts and Diazo Esters: Synthesis of Fully Substituted Pyrazoles under Room Temperature
  作者：Ying Shao、Hao Zheng、Junfeng Qian、Xiaobing Wan

  DOI：10.1021/acs.orglett.8b00750

  日期：2018.4.20

  A novel one-pot synthesis for fully substituted pyrazoles has been well developed via the in situ generation of nitrilimines from aryldiazonium salts and diazo esters and a subsequent cycloaddition with 1,3-dicarbonyl compounds. High yields, mild conditions, wide substrate scope, and operational simplicity are the significant advantages of this methodology.

  通过从芳基重氮盐和重氮酯原位生成腈亚胺以及随后与1,3-二羰基化合物进行环加成反应，已开发出一种完全取代的吡唑的新型一锅合成方法。高产率，温和的条件，广泛的底物范围和操作简便性是该方法的显着优势。
• Efficient Synthesis and Antimicrobial Evaluation of New Azolopyrimidines‐Bearing Pyrazole Moiety
  作者：Abdou O. Abdelhamid、Sobhi M. Gomha、Waleed A. M. A. El‐Enany

  DOI：10.1002/jhet.3638

  日期：2019.9

  enone derivatives was used as a precursor for synthesis of various fused azolopyrimidine ring systems as pyrazolopyrimidines, triazolopyrimidines, and pyrimidobenzimidazoles following many procedures. The identity of the prepared compounds was elucidated by their spectral data and elemental analyses. The in vitro antimicrobial activity of 13 new compounds was evaluated, and many derivatives showed

  使用3-羟基-1-（1-芳基-5-甲基吡唑基）丙烯酮衍生物的钠盐作为前体，可以按照许多步骤合成各种稠合的偶氮嘧啶环系统，如吡唑并嘧啶，三唑并嘧啶和嘧啶并苯并咪唑。通过其光谱数据和元素分析阐明了所制备化合物的身份。在体外的13种新的化合物的抗微生物活性进行了评价，并且许多衍生物显示出优良至适中的活性。