(E)-3-(5-pyrimidinyl)acrylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (E)-3-(5-pyrimidinyl)acrylic acid
• 英文别名: β-(5-Pyrimidinyl)acrylic acid；(E)-3-(pyrimidin-5-yl)acrylic acid；(E)-3-pyrimidin-5-ylprop-2-enoic acid
• 化学式: C₇H₆N₂O₂
• 分子量: 150.137
• InChiKey: XZAOEYWVIVLYAL-OWOJBTEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(5-pyrimidinyl)acrylic acid 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (E)-4-methyl-3-(3-(pyrimidin-5-yl)acrylamido)-N-(p-tolyl)benzamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel acrylamide analogues as inhibitors of BCR–ABL kinase

  摘要：

  A series of acrylamide analogues were designed and synthesized from Imatinib and Nilotinib as novel BCR-ABL inhibitors by application of the principle of nonclassical electronic isostere. All new compounds were evaluated for their inhibitory effects on the activity of BCR-ABL kinase and the proliferation of K562 leukemia cancer cells in vitro. The acrylamide analogues in which the substituent in C ring was trifluoromethyl group were identified as highly potent BCR-ABL kinase inhibitors. Compound 13f exhibited an IC50 value as low as 20.6 nM in ABL kinase inhibition and an IC50 value of 32.3 nM for antiproliferative activity, about 10.5-fold and 12-fold lower than those of Imatinib respectively. These results suggest that compound 13f is a promising candidate as a novel BCR-ABL kinase inhibitor for further development. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.044
• 作为产物：
  描述：

  ethyl 3-(5-pyrimidinyl)acrylate 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以58%的产率得到(E)-3-(5-pyrimidinyl)acrylic acid
  参考文献：
  名称：

  Acrylamide derivatives as antiallergic agents. III. Synthesis and structure-activity relationships of N-(4-(4-diphenylmethyl-1-piperazinyl)butyl)- and N-(4-(4-diphenylmethylene-1-piperidyl)butyl)-3-heteroacrylacrylamides.

  摘要：

  制备了一系列新的 3-杂芳基丙烯酰胺 2 和 4，并测试了它们对大鼠被动皮肤过敏性休克（PCA）反应和 5-脂氧合酶（5-LO）的抑制活性。大多数化合物的抗 PCA 活性优于或相当于酮替芬，并具有 5-LO 抑制活性。3-teroarylacrylamide 衍生物（包括 3-(3-吡啶基)丙烯酰胺）代表了一类结构新颖的化合物，不仅具有体内抗PCA 活性，而且还具有体外 5-LO 摄取活性。

  DOI：

  10.1248/cpb.37.684

文献信息

• Design, synthesis and X-ray crystallographic study of NAmPRTase inhibitors as anti-cancer agents
  作者：Hyun You、Hyung-Seop Youn、Isak Im、Man-Ho Bae、Sang-Kook Lee、Hyojin Ko、Soo Hyun Eom、Yong-Chul Kim

  DOI：10.1016/j.ejmech.2011.01.034

  日期：2011.4

  against the proliferation of cancer cells and human NAmPRTase. Among them, compound 7 showed similar anti-cancer and enzyme inhibitory activities to compound 1. Further investigation of compound 7 with X-ray analysis revealed a co-crystal structure in complex with human NAmPRTase, suggesting that Asp219 in the active site of the enzyme could contribute to an additional interaction with the pyrrole nitrogen

  NAmPRTase（PBEF / Visfatin）在NAD +生物合成的挽救途径中起着关键作用。NAmPRTase一直是通过降低血浆NAD +水平诱导肿瘤细胞凋亡的抗癌剂的有吸引力的靶标。在本报告中，合成了一系列已知的NAmPRTase抑制剂FK866（1）的结构类似物，并测试了其对癌细胞和人NAmPRTase增殖的抑制活性。其中，化合物7显示出与化合物1类似的抗癌和酶抑制活性。化合物7的进一步研究X射线分析显示与人NAmPRTase复合的共晶体结构，这表明该酶活性位点中的Asp219可能有助于与化合物7的吡咯氮进行额外的相互作用。
• Pyrimidinone compounds
  申请人：SmithKline Beecham p.l.c.

  公开号：US20040167142A1

  公开（公告）日：2004-08-26

  Pyrimidinone compounds of formula (I) are inhibitors of the enzyme Lp-PLA 2 and of use in therapy, in particular for treating atherosclerosis. 1

  式（I）的嘧啶酮化合物是Lp-PLA2酶的抑制剂，可用于治疗，特别是用于治疗动脉粥样硬化。
• Identification of a Potent Oridonin Analogue for Treatment of Triple-Negative Breast Cancer
  作者：Hong Yao、Shaowen Xie、Xiaoqian Ma、Junkai Liu、Hongyu Wu、Aijun Lin、Hequan Yao、Dahong Li、Shengtao Xu、Dong-Hua Yang、Zhe-Sheng Chen、Jinyi Xu

  DOI：10.1021/acs.jmedchem.0c00408

  日期：2020.8.13

  The natural product oridonin is reported to be a potential anti-TNBC agent. However, its moderate activity and complex structure hampered its clinical application. In this study, the novel oridonin analogues were first identified by removal of multiple hydroxyl groups and structural simplification of oridonin. The representative analogue 20 exhibited potent anticancer effects. Further structural modification

  三阴性乳腺癌（TNBC）是最具侵入性和转移性的乳腺癌之一，没有安全有效的治疗药物。天然产物冬凌草甲素据报道是潜在的抗TNBC剂。但是，其中等活性和复杂结构阻碍了其临床应用。在这项研究中，新的冬凌草甲素类似物首先通过去除多个羟基和简化冬凌草甲素的结构来鉴定。代表性类似物20表现出有效的抗癌作用。在20上进一步的结构修饰产生了最有效的衍生物56，其比TNBC细胞系HCC1806中的冬凌草甲素具有120倍的有效抗增殖活性。重要的是化合物56在TNBC异种移植裸鼠中显示出比紫杉醇更有效的抗癌活性。此外，56可以减弱MMP-2，MMP-9，p-FAK和整联蛋白β1的表达，从而抑制TNBC细胞的转移。所有结果表明，化合物56作为TNBC治疗的有前途的候选药物可能值得进一步研究。
• Acrylamide Derivative And Use Thereof In Manufacture Of Medicament
  申请人：Sun Shuping

  公开号：US20120116075A1

  公开（公告）日：2012-05-10

  An acrylamide derivative represented by formula (I), pharmaceutically acceptable salts and solvates thereof, as well as a medicament containing said acrylamide derivative or its pharmaceutically acceptable salts as the active ingredient, which can be used to treat disorders associated with tyrosine kinase especially Bcr-Abl, including proliferative disorders such as cancers, and inflammation and the like are provided.

  由公式(I)表示的丙烯酰胺衍生物，其药学上可接受的盐和溶剂，以及包含该丙烯酰胺衍生物或其药学上可接受的盐作为活性成分的药物剂，可用于治疗与酪氨酸激酶尤其是Bcr-Abl相关的紊乱，包括增生性疾病如癌症、炎症等。
• Bicyclic Piperidines <i>via</i> [2 + 2] Photocycloaddition
  作者：Valeriya Shcherbakova、Dmitry Dibchak、Mariya Snisarenko、Yevhen Skalenko、Aleksandr V. Denisenko、Anastasiia S. Kuznetsova、Pavel K. Mykhailiuk

  DOI：10.1021/acs.joc.0c02355

  日期：2021.2.5

  A synthetic strategy to fused bicyclic piperidines—building blocks for medicinal chemistry—is developed. The key step was an intramolecular [2 + 2]-photocyclization. The photochemical step was performed on a gram scale. Crystallographic analysis of the obtained compounds revealed that they occupy a novel chemical space and can be considered as elongated analogues of 3-substituted piperidines.

  提出了一种融合双环哌啶的合成策略-药用化学的基础。关键步骤是分子内[2 + 2]-光环化。光化学步骤以克为单位进行。所得化合物的晶体学分析表明，它们占据了新的化学空间，可以被认为是3-取代的哌啶的细长类似物。