benzyl-(4-chloro-6-methylpyrimidin-2-yl)amine | 25710-11-6

• 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: benzyl-(4-chloro-6-methylpyrimidin-2-yl)amine
• 英文别名: N-benzyl-4-chloro-6-methyl-pyrimidin-2-amine；N-benzyl-4-chloro-6-methylpyrimidin-2-amine；2-benzylamine-6-methyl-4-chloropyrimidine；2-benzylamino-4-chloro-6-methylpyrimidine；2-benzylamino-6-methyl-4-chloropyrimidine；benzyl-(4-chloro-6-methyl-pyrimidin-2-yl)-amine
• CAS: 25710-11-6
• 化学式: C₁₂H₁₂ClN₃
• mdl: MFCD00452902
• 分子量: 233.7
• InChiKey: CXCLPGFYAWUDEC-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：
  0.166
• 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：

  benzyl-(4-chloro-6-methylpyrimidin-2-yl)amine 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 2-benzylamino-6-methyl-4-phenylaminopyrimidine
  参考文献：
  名称：

  Effect of halogen atom localization on the level of antimycobacterial activity of 2-amino-4-arylamino-6-methylpyrimidines

  摘要：

  Several hydrochlorides of 2-alkyl(cycloalkyl, aralkyl)-5-bromo-6-methyl-4-phenylaminopyrimidines have been synthesized as isosteric analogs of the corresponding 2-alkyl(cycloalkyl, aralkyl)-4-(3-bromophenyl)amino-6-methylpyrimidine hydrochlorides. Moving the bromine atom from the benzene ring into the heterocycle is accompanied by a significant decrease in the level of antimycobacterial activity.

  DOI：

  10.1134/s1070363210040237
• 作为产物：
  描述：

  2-benzylamino-6-methyl-4(3H)-pyrimidinone 在 三氯氧磷 作用下， 反应 1.0h， 以49%的产率得到benzyl-(4-chloro-6-methylpyrimidin-2-yl)amine
  参考文献：
  名称：

  Synthesis and antimicobacterial activity of 2-substituted 4-arylamino-6-methylpyrimidines

  摘要：

  2-Substituted 4-arylamino-6-methylpyrimidines were synthesized by stepwise modification of the structure of 6-methyl-2-thiouracyl through the intermediate 2-(ar)alkylthio-6-methyl-4-chloropyrimidines. Some of the compounds synthesized exhibit expressed antimycobacterial activity.

  DOI：

  10.1134/s1070363208100216

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。
• [EN] INDOLE/BENZIMIDAZOLE COMPOUNDS AS mTOR KINASE INHIBITORS<br/>[FR] COMPOSÉS D'INDOLE OU BENZIMIDAZOLE CONVENANT COMME INHIBITEURS DE LA KINASE MTOR
  申请人：AMGEN INC

  公开号：WO2010096314A1

  公开（公告）日：2010-08-26

  The present invention provides compounds that are kinase inhibitors, specifically PIK kinase inhibitors, more specifically, mTOR inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PIK kinase inhibitors, more specifically, mTOR such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本发明提供了一种激酶抑制剂化合物，具体来说是PIK激酶抑制剂，更具体地说是mTOR抑制剂，因此适用于治疗通过抑制激酶治疗的疾病，特别是PIK激酶抑制剂，更具体地说是mTOR抑制剂，例如癌症。还提供了含有这些化合物的药物组合物和制备这些化合物的方法。
• Indole/Benzimidazole Compounds as mTOR Kinase Inhibitors
  申请人：Boezio Alessandro

  公开号：US20120165334A1

  公开（公告）日：2012-06-28

  The present invention provides compounds that are kinase inhibitors, specifically PIK kinase inhibitors, more specifically, mTOR inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PIK kinase inhibitors, more specifically, mTOR such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本发明提供了一种激酶抑制剂，具体地说是PIK激酶抑制剂，更具体地说是mTOR抑制剂，因此适用于治疗通过抑制激酶，特别是PIK激酶抑制剂，更具体地说是mTOR抑制剂可治疗的疾病，例如癌症。还提供了含有这种化合物的药物组合物和制备这种化合物的方法。
• 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.