4-chloro-2-cyclohexylamino-6-methylpyrimidine | 54093-14-0

• 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: 4-chloro-2-cyclohexylamino-6-methylpyrimidine
• 英文别名: (4-chloro-6-methyl-pyrimidine-2-yl)-cyclohexylamine；(4-chloro-6-methylpyrimidin-2-yl)cyclohexylamine；6-methyl-4-chloro-2-cyclohexylaminopyrimidine；4-chloro-N-cyclohexyl-6-methylpyrimidin-2-amine
• CAS: 54093-14-0
• 化学式: C₁₁H₁₆ClN₃
• 分子量: 225.721
• InChiKey: RYWXPGDRUMNMJE-UHFFFAOYSA-N

物化性质

• 沸点：
  374.4±34.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 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：

  4-chloro-2-cyclohexylamino-6-methylpyrimidine 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 sodium hydroxide 作用下， 以 四氯化碳 、 水 为溶剂， 反应 1.0h， 生成 5-bromo-6-methyl-4-phenylamino-2-cyclohexylaminopyrimidine hydrochloride
  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-cyclohexylamino-6-methyl-4(3H)-pyrimidinone hydrochloride 在 三氯氧磷 作用下， 反应 1.0h， 生成 4-chloro-2-cyclohexylamino-6-methylpyrimidine
  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

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。
• Identification of Aminopyrimidine Regioisomers via Line Broadening Effects in 1H and 13C NMR Spectroscopy
  作者：James Garner、Tim Hill、Luke Odell、Paul Keller、Jody Morgan、Adam McCluskey

  DOI：10.1071/ch03316

  日期：——

  Primary amines substituted at the 4-position exhibited room-temperature line broadening effects in both 1H and 13C NMR spectroscopy due to the presence of rotamers, but these effects were not observed for substituents in the 2-position. This provided a simple diagnostic tool for the identification of regioisomers, a determination which would otherwise have required two-dimensional experiments.

  作为我们药物化学计划的一部分，合成了取代的单氨基和二氨基嘧啶。由于存在旋转异构体，在 4 位取代的伯胺在 1H 和 13C NMR 光谱中表现出室温谱线展宽效应，但在 2 位取代基没有观察到这些效应。这为识别区域异构体提供了一种简单的诊断工具，否则需要二维实验才能确定。
• Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca²⁺-activated K⁺channels
  作者：C Hougaard、B L Eriksen、S Jørgensen、T H Johansen、T Dyhring、L S Madsen、D Strøbaek、P Christophersen

  DOI：10.1038/sj.bjp.0707281

  日期：2007.7

  Background and purpose:Positive modulators of small conductance Ca2+‐activated K+ channels (SK1, SK2, and SK3) exert hyperpolarizing effects that influence the activity of excitable and non‐excitable cells. The prototype compound 1‐EBIO or the more potent compound NS309, do not distinguish between the SK subtypes and they also activate the related intermediate conductance Ca2+‐activated K+ channel (IK). This paper demonstrates, for the first time, subtype‐selective positive modulation of SK channels.Experimental approach:Using patch clamp and fluorescence techniques we studied the effect of the compound cyclohexyl‐[2‐(3,5‐dimethyl‐pyrazol‐1‐yl)‐6‐methyl‐pyrimidin‐4‐yl]‐amine (CyPPA) on recombinant hSK1‐3 and hIK channels expressed in HEK293 cells. CyPPA was also tested on SK3 and IK channels endogenously expressed in TE671 and HeLa cells.Key results:CyPPA was found to be a positive modulator of hSK3 (EC50 = 5.6 ± 1.6 μM, efficacy 90 ± 1.8 %) and hSK2 (EC50 = 14 ± 4 μM, efficacy 71 ± 1.8 %) when measured in inside‐out patch clamp experiments. CyPPA was inactive on both hSK1 and hIK channels. At hSK3 channels, CyPPA induced a concentration‐dependent increase in the apparent Ca2+‐sensitivity of channel activation, changing the EC50(Ca2+) from 429 nM to 59 nM.Conclusions and implications:As a pharmacological tool, CyPPA may be used in parallel with the IK/SK openers 1‐EBIO and NS309 to distinguish SK3/SK2‐ from SK1/IK‐mediated pharmacological responses. This is important for the SK2 and SK1 subtypes, since they have overlapping expression patterns in the neocortical and hippocampal regions, and for SK3 and IK channels, since they co‐express in certain peripheral tissues.British Journal of Pharmacology (2007) 151, 655–665; doi:10.1038/sj.bjp.0707281
• [DE] NEUE PYRIMIDINE, DEREN HERSTELLUNG UND VERWENDUNG<br/>[EN] NOVEL PYRIMIDINES, THE PRODUCTION THEREOF AND THEIR USE<br/>[FR] NOUVELLES PYRIMIDINES, LEUR PRODUCTION ET LEUR UTILISATION
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2000027826A1

  公开（公告）日：2000-05-18

  Die vorliegende Erfindung betrifft neue Pyrimidine der allgemeinen Formel (I), in der Ra bis Rd, A und X wie im Anspruch 1 definiert sind, deren Tautomere, deren Stereoisomere, deren Gemische und deren Salze, welche wertwolle Eigenschaften aufweisen, deren Herstellung, die die pharmakologisch wirksamen Verbindungen enthaltende Arzneimittel und deren Verwendung. Die Verbindungen der allgemeinen Formel (I), in denen Rc eine Cyanogruppe darstellt, stellen wertvolle Zwischenprodukte zur Herstellung der übrigen Verbindungen der allgemeinen Formel (I) dar, welche wertvolle pharmakologische Eigenschaften aufweisen, insbesondere eine antithrombotische Wirkung.
• Effect of halogen atom localization on the level of antimycobacterial activity of 2-amino-4-arylamino-6-methylpyrimidines
  作者：A. V. Erkin、V. I. Krutikov

  DOI：10.1134/s1070363210040237

  日期：2010.4

  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.