2-chloro-4-methyl-6-(4-methylpiperazin-1-yl)pyrimidine | 917021-26-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-chloro-4-methyl-6-(4-methylpiperazin-1-yl)pyrimidine
• CAS: 917021-26-2
• 化学式: C₁₀H₁₅ClN₄
• 分子量: 226.709
• InChiKey: NQOULLHASCYNNH-UHFFFAOYSA-N

物化性质

• 沸点：
  379.5±42.0 °C(Predicted)
• 密度：
  1.209±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  32.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-4-methyl-6-(4-methylpiperazin-1-yl)pyrimidine 、 4,4'-(1,5-戊二氧基)二苯胺 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以71%的产率得到4-methyl-N-[4-[5-[4-[[4-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl]amino]phenoxy]pentoxy]phenyl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine
  参考文献：
  名称：

  A natural product inspired hybrid approach towards the synthesis of novel pentamidine based scaffolds as potential anti-parasitic agents

  摘要：

  A natural product inspired molecular hybridization approach led us to a series of novel pentamidine based pyrimidine and chalcone scaffolds. All the hybrids were evaluated for their anti-leishmanial potential. Most of the screened compounds have showed significant in vitro anti-leishmanial activity with less cytotoxicity in comparison to the standard drugs (pentamidine, sodium stibogluconate, and miltefosine). Additionally, anti-malarial screening of these compounds was also done and four compounds have shown superior activity against chloroquine resistance strain (K1) of Plasmodium falciparum. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.101
• 作为产物：
  描述：

  N-甲基哌嗪 、 2,4-二氯-6-甲基嘧啶 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以55%的产率得到2-chloro-4-methyl-6-(4-methylpiperazin-1-yl)pyrimidine
  参考文献：
  名称：

  Pyrimidine compounds

  摘要：

  这项发明涉及一种治疗炎症性疾病或免疫性疾病、发育性或退行性疾病或组织损伤的方法。该方法包括向需要的受试者施用一种或多种式(I)化合物的有效量。该式中的每个变量在说明书中有定义。

  公开号：

  US20060281712A1

文献信息

• [EN] GCN2 INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE GCN2 ET LEURS UTILISATIONS
  申请人：MERCK PATENT GMBH

  公开号：WO2019148132A1

  公开（公告）日：2019-08-01

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用它们的方法。
• Pyrimidine-Based Inhibitors of Dynamin I GTPase Activity: Competitive Inhibition at the Pleckstrin Homology Domain
  作者：Luke R. Odell、Mohammed K. Abdel-Hamid、Timothy A. Hill、Ngoc Chau、Kelly A. Young、Fiona M. Deane、Jennette A. Sakoff、Sofia Andersson、James A. Daniel、Phillip J. Robinson、Adam McCluskey

  DOI：10.1021/acs.jmedchem.6b01422

  日期：2017.1.12

  dynamin localization to the plasma membrane via the PH domain and implicate this mechanism in the inhibition of CME. We have used a computational approach of binding site identification, docking, and interaction energy calculations to design and synthesize a new library of aminopyrimidine analogues targeting site-2 of the pleckstrin homology (PH) domain. The optimized analogues showed low micromolar inhibition

  大型GTP酶动力蛋白在网格蛋白介导的内吞作用（CME）期间介导膜裂变。据报道，氨基嘧啶化合物可通过PH结构域破坏动力蛋白定位于质膜，并在抑制CME中发挥作用。我们已经使用了结合位点识别，对接和相互作用能计算的一种计算方法来设计和合成靶向pleckstrin同源性（PH）域的site-2的氨基嘧啶类似物的新文库。优化的类似物对动力蛋白I（IC 50 = 10.6±1.3至1.6±0.3μM）和CME（IC 50（CME））的微摩尔抑制作用均较低= 65.9±7.7至3.7±1.1 mM），这使该系列成为尚未报道的更有效的动力和CME抑制剂之一。在基于CME和细胞生长抑制的测定中，获得的数据与动力抑制作用一致。CEREP ExpresS分析鉴定了胆囊收缩素，多巴胺D 2，组胺H 1和H 2，黑皮质素，褪黑激素，毒蕈碱M 1和M 3，神经激肽，阿片样物质KOP和5-羟色胺受体的脱靶作用。
• Pyrimidyn‐Based Dynamin Inhibitors as Novel Cytotoxic Agents
  作者：Luke R. Odell、Ngoc Chau、Cecilia C. Russell、Kelly A. Young、Jayne Gilbert、Phillip J. Robinson、Jennette A. Sakoff、Adam McCluskey

  DOI：10.1002/cmdc.202100560

  日期：2022.1.5

  Five focused libraries: A series of substituted pyrimidines were prepared as dynamin GTPase inhibitors. Dynamin inhibition correlated with the observed cytotoxicity, consistent with the know role of dynamin in cell division.

  五个重点文库：制备了一系列取代的嘧啶作为动力蛋白 GTP 酶抑制剂。动力蛋白抑制与观察到的细胞毒性相关，这与动力蛋白在细胞分裂中的已知作用一致。
• Discovery of Trifluoromethyl(pyrimidin-2-yl)azetidine-2-carboxamides as Potent, Orally Bioavailable TGR5 (GPBAR1) Agonists: Structure–Activity Relationships, Lead Optimization, and Chronic In Vivo Efficacy
  作者：Dean P. Phillips、Wenqi Gao、Yang Yang、Guobao Zhang、Isabelle K. Lerario、Thomas L. Lau、Jiqing Jiang、Xia Wang、Deborah G. Nguyen、B. Ganesh Bhat、Carol Trotter、Heather Sullivan、Gustav Welzel、Jannine Landry、Yali Chen、Sean B. Joseph、Chun Li、W. Perry Gordon、Wendy Richmond、Kevin Johnson、Angela Bretz、Badry Bursulaya、Shifeng Pan、Peter McNamara、H. Martin Seidel

  DOI：10.1021/jm401731q

  日期：2014.4.24

  Activation of the G-protein coupled receptor (GPCR) Takeda G-protein receptor 5 (TGR5), also known as G-protein bile acid receptor 1 (GPBAR1), has been shown to play a key role in pathways associated with diabetes, metabolic syndrome, and autoimmune disease. Nipecotamide 5 was identified as an attractive starting point after a high-throughput screen (HTS) for receptor agonists. A comprehensive hit-to-lead effort culminated in the discovery of 45h as a potent, selective, and bioavailable TGR5 agonist to test in preclinical metabolic disease models. In genetically obese mice (ob/ob), 45h was as effective as a dipeptidyl peptidase-4 (DPP-4) inhibitor at reducing peak glucose levels in an acute oral glucose tolerance test (OGTT), but this effect was lost upon chronic dosing.
• PYRIMIDINE COMPOUNDS AS CHEMOKINE RECEPTORS INHIBITORS
  申请人：Taigen Biotechnology

  公开号：EP1890703B1

  公开（公告）日：2016-05-11