苄基-(2-氯-6-甲基嘧啶-4-基)胺 | 25710-10-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 苄基-(2-氯-6-甲基嘧啶-4-基)胺
• 英文名称: N-benzyl-2-chloro-6-methylpyrimidin-4-amine
• 英文别名: Benzyl-(2-chloro-6-methylpyrimidin-4-yl)amine
• CAS: 25710-10-5
• 化学式: C₁₂H₁₂ClN₃
• 分子量: 233.7
• InChiKey: FRIAVOGKGFQNOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  苄基-(2-氯-6-甲基嘧啶-4-基)胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 过氧化脲素 、 potassium carbonate 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 为溶剂， 反应 12.0h， 生成 1-[4-(benzylamino)-6-methylpyrimidin-2-yl]-2-methyl-1H-indole-4-carboxamide
  参考文献：
  名称：

  [EN] MONOCYCLIC PYRIMIDINE/PYRIDINE COMPOUNDS AS INHIBITORS OF P97 COMPLEX
  [FR] COMPOSÉS MONOCYCLIQUES PYRIMIDINE/PYRIDINE COMME INHIBITEURS DU COMPLEXE P97

  摘要：

  在4位上具有苄胺取代基的单环嘧啶和吡啶化合物，以及在2位上具有5:6双环杂芳基取代基的嘧啶或吡啶环，还可以在环的其他位置取代烷基、官能基和/或芳香基成分。这些化合物是含有p97的AAA蛋白酶复合物的抑制剂，并且是用于治疗与p97生物活性相关的疾病如癌症的有效药物。

  公开号：

  WO2015089218A1
• 作为产物：
  描述：

  2,4-二氯-6-甲基嘧啶 、 苄胺 在 三乙胺 作用下， 以 乙腈 为溶剂， 以73%的产率得到苄基-(2-氯-6-甲基嘧啶-4-基)胺
  参考文献：
  名称：

  Pyrazolyl-Pyrimidines as Potassium Channel Modulating Agents and Their Medical Use

  摘要：

  这项发明涉及新型钾通道调节剂，以及它们在制备药物组合物中的应用。此外，该发明针对用于治疗或缓解与钾通道活性相关的疾病或障碍的药物组合物，特别是呼吸道疾病、癫痫、抽搐、血管痉挛、冠状动脉痉挛、肾功能紊乱、多囊肾病、膀胱痉挛、尿失禁、膀胱排出道梗阻、肠易激综合征、胃肠功能紊乱、分泌性腹泻、缺血、脑缺血、缺血性心脏病、心绞痛、冠心病、创伤性脑损伤、精神病、精神分裂症、焦虑、抑郁症、痴呆、记忆和注意力缺陷、阿尔茨海默病、痛经、嗜睡症、雷诺氏病、间歇性跛行、干燥综合征、偏头痛、心律失常、高血压、缺席性癫痫发作、肌肉肌无力症、干燥综合症、2型糖尿病、胰岛素高血症、早产、秃头、癌症、免疫抑制或疼痛。

  公开号：

  US20090036475A1

文献信息

• 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。
• Crystal and Molecular Structures of Benzyl-(2-chloro-6-methylpyrimidin-4-yl)amine and Benzyl-(4-chloro-6-methylpyrimidin-2-yl)amine: Confirmation of Computationally Predicted Restricted Rotation
  作者：Luke R. Odell、Adam McCluskey、Timothy W. Failes、Edward R. T. Tiekink

  DOI：10.1007/s10870-007-9253-2

  日期：2007.11.7

  Crystal structures for the isomeric compounds benzyl-(2-chloro-6-methylpyrimidin-4-yl)amine (1), as its hemi-hydrate, and benzyl-(4-chloro-6-methylpyrimidin-2-yl)amine (2) have been determined. Conformational differences lead to multiple molecules, i.e. two and three, in their respective structures. Layers feature in each of the crystal structures and are stabilized by substantial hydrogen-bonding interactions. Compound (1) crystallizes as a hemi-hydrate in the triclinic space group P-1 with a = 8.667(5) Å, b = 11.421(7) Å, c = 12.954(8) Å, α = 78.330(10)°, β = 84.553(10)°, γ = 75.510(9)°, and Z = 4. Compound (2) crystallizes in the monoclinic space group P21/c with a = 10.740(3) Å, b = 21.487(6) Å, c = 14.914(4) Å, β = 95.014(5)°, and Z = 12. Substantial hydrogen-bonding interactions leading to layer structures feature in each of the crystal structures of the isomeric title compounds.

  异构化合物苄基-(2-氯-6-甲基嘧啶-4-基)胺 (1) 及其半水合物，以及苄基-(4-氯-6-甲基嘧啶-2-基)胺 (2) 的晶体结构已经确定。构象差异导致它们各自的结构中存在多个分子，即两个和三个。每种晶体结构都具有层状特征，并由大量的氢键相互作用稳定。化合物 (1) 以半水合物的形式在三斜空间群 P-1 中结晶，其晶格参数为 a = 8.667(5) Å，b = 11.421(7) Å，c = 12.954(8) Å，α = 78.330(10)°，β = 84.553(10)°，γ = 75.510(9)°，Z = 4。化合物 (2) 在单斜空间群 P21/c 中结晶，其晶格参数为 a = 10.740(3) Å，b = 21.487(6) Å，c = 14.914(4) Å，β = 95.014(5)°，Z = 12。这两种异构标题化合物的晶体结构中均具有由大量氢键相互作用形成的层状结构。
• A natural product inspired hybrid approach towards the synthesis of novel pentamidine based scaffolds as potential anti-parasitic agents
  作者：Vikas Tyagi、Shahnawaz Khan、Rahul Shivahare、Khushboo Srivastava、Suman Gupta、Saqib Kidwai、Kumkum Srivastava、S.K. Puri、Prem M.S. Chauhan

  DOI：10.1016/j.bmcl.2012.10.101

  日期：2013.1

  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.
• Synthesis and antiplasmodial activity of novel 2,4-diaminopyrimidines
  作者：Derek C. Martyn、Amarjit Nijjar、Cassandra A. Celatka、Ralph Mazitschek、Joseph F. Cortese、Erin Tyndall、Hanlan Liu、Maria M. Fitzgerald、Thomas J. O’Shea、Sanjay Danthi、Jon Clardy

  DOI：10.1016/j.bmcl.2009.10.133

  日期：2010.1

  Two sets of diaminopyrimidines, totalling 45 compounds, were synthesized and assayed against Plasmodium falciparum. The SAR was relatively shallow, with only the presence of a 2-(pyrrolidin-1-yl)ethyl group at R-2 significantly affecting activity. A subsequent series addressed high Log D values by introducing more polar side groups, with the most active compounds possessing diazepine and N-benzyl-4-aminopiperidyl groups at R-1/R-2. A final series attempted to address high in vitro microsomal clearance by replacing the C6-Me group with CF3, however antiplasmodial activity decreased without any improvement in clearance. The C6-CF3 group decreased hERG inhibition, probably as a result of decreased amine basicity at C2/C4. (C) 2009 Elsevier Ltd. All rights reserved.
• 2,4-Diamino-6-methylpyrimidines for the potential treatment of Chagas’ disease
  作者：Michael G. Thomas、Manu De Rycker、Ignacio Cotillo Torrejon、John Thomas、Jennifer Riley、Daniel Spinks、Kevin D. Read、Tim J. Miles、Ian H. Gilbert、Paul G. Wyatt

  DOI：10.1016/j.bmcl.2018.08.005

  日期：2018.10

  Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, affects 8-10 million people across the Latin American population and is responsible for around 12,500 deaths per annum. The current frontline treatments, benznidazole and nifurtimox, are associated with side effects and lack efficacy in the chronic stage of the disease, leading to an urgent need for new treatments. A high throughput screening campaign against the physiologically relevant intracellular form of the parasite identified a series of 2,4-diamino-6-methylpyrimidines. Demonstrating the series did not work through the anti-target TcCYP51, and was generally cytocidal, confirmed its suitability for further development. This study reports the optimisation of selectivity and metabolic stability of the series and identification of a suitable lead for further optimisation.