2-chloro-5-nitro-N-(2,4,6-trimethylphenyl)-4-pyrimidinamine

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-chloro-5-nitro-N-(2,4,6-trimethylphenyl)-4-pyrimidinamine
• 英文别名: 2-chloro-N-mesityl-5-nitropyrimidin-4-amine；2-chloro-5-nitro-N-(2,4,6-trimethylphenyl)pyrimidin-4-amine
• 化学式: C₁₃H₁₃ClN₄O₂
• 分子量: 292.725
• InChiKey: ZFKIVUSFSXPZKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-5-nitro-N-(2,4,6-trimethylphenyl)-4-pyrimidinamine 在 tin(II) chloride dihdyrate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 6.0h， 生成 1-(2-((5-amino-4-(mesitylamino)pyrimidin-2-yl)amino)ethyl)pyrimidine-2,4-(1H,3H)-dione
  参考文献：
  名称：

  Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization

  摘要：

  A novel series of uracil-bearing DAPYs derivatives were designed and synthesized via structure-based molecular hybridization to discover compounds with improved anti-resistance profiles. Anti-HIV activity of the designed compounds was tested in MT-4 cell cultures. The most promising compound 16d showed excellent activity with EC50 value of 5.6 nM against wide-type HIV-1 and low cytotoxicity (SI > 50000). Activity against the clinic prevalent mutant strains was also tested, suggesting that 16d was sensitive to E138K (EC50 = 34.2 nM). Primary drug-like properties, such as water solubility and logP, were evaluated by experiment or calculation, which indicated that introducing an uracil can improve solubility. The molecular modeling accompanied with the preliminary SAR correlations paved the way for the next round of rational design of potent anti-HIV agents. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.047
• 作为产物：
  描述：

  2,4,6-三甲基苯胺 、 2,4-二氯-5 硝基嘧啶 以 1,4-二氧六环 为溶剂， 反应 16.0h， 生成 2-chloro-5-nitro-N-(2,4,6-trimethylphenyl)-4-pyrimidinamine
  参考文献：
  名称：

  [EN] TRIAZOLOPYRIMIDINE DERIVATIVES AS GLYCOGEN SYNTHASE KINASE 3 INHIBITORS
  [FR] DERIVES DE TRIAZOLOPYRIMIDINE EN TANT QU'INHIBITEURS DE GLYCOGENE SYNTHASE KINASE 3

  摘要：

  这项发明涉及式(I)的化合物，一种N-氧化物，一种药用可接受的加合盐，一种季铵盐和其立体化学异构体形式，其中环A代表苯基、吡啶基、嘧啶基、吡啶并嘧啶基或吡嗪基；R1代表氢；芳基；甲酰基；Cl.6烷基羰基，C1-6烷基；C1-6烷氧羰基；C1-6烷基取代的甲酰基，C1-6烷基羰基，C1-6烷氧羰基，C1-6烷基羰氧基；或C1-6烷氧基C1-6烷基羰基，可选地取代C1-6烷氧羰基；X代表直链键；-(CH2)n3或-(CH2)m4-X1a-X1b-；R2代表C3-7环烷基；苯基；含有至少一个杂原子的4,5,6-或7-成员单环杂环烃，所述杂原子选自O、S或N；苯并噁唑基或式(a-1)的基团，其中所述R2取代基可选择地被取代；R3代表卤素；羟基；可选地取代的C1-6烷基；C2-6烯基或C2-6炔基，每种可选择地被取代；可选择地取代的多卤C1-6烷基；可选择地取代的C1-6烷氧基；可选择地取代的多卤C1-6烷氧基；C1-6烷基硫；多卤C1-6烷基硫；C1-6烷氧羰基；C1-6烷基羰氧基；C1-6烷氧羰基；多卤C1-6烷基羰基；氰基；羧基；芳基氧基；芳基硫；芳基羰基；NR6b R7b；C(=O)-NR 6b R 7b；-NR5-C(=O)R5；'-S(=O)nl-R8a；-NR5S(=O)nl -R 8a；-NR 5 -S(=O)nl -R 8a；-S-CN；-NR5 -CN；R4代表氢；卤素；羟基；可选地取代的C1-4烷基；C2-4烯基或C2-4炔基，每种可选择地被取代；多卤C1-3烷基；可选地取代的C1-4烷氧基；多卤C1-3烷氧基；C1-4烷基硫；多卤C1-3烷基硫；C1-4烷氧羰基；C1-4烷基羰氧基；C1-4烷基羰基；多卤C1-4烷基羰基；硝基；氰基；羧基；NR10 R11；C(=O)NR10-R11；NR5-C(=O)-NR10R11；-NR5 -C(=O)-R5；-S(=O)nl,-R12 -NR5-S(=O)nI-R12；-S-CN；-NR5 -CN；它们的使用，包括它们的药用组合物和其制备方法。

  公开号：

  WO2005012307A1

文献信息

• [EN] TRIAZOLOPYRIMIDINE DERIVATIVES AS GLYCOGEN SYNTHASE KINASE 3 INHIBITORS<br/>[FR] DERIVES DE TRIAZOLOPYRIMIDINE EN TANT QU'INHIBITEURS DE GLYCOGENE SYNTHASE KINASE 3
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2005012307A1

  公开（公告）日：2005-02-10

  This invention concerns a compound of formula (I), a N-oxide, a pharmaceutically acceptable addition salt, a quaternary arnine and a stereochernic ally isomeric form thereof, wherein ring A represents phenyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl; R1 represents hydrogen; aryl; formyI; Cl.6alkylcarbonyl, C1-6alkyl; C1-6alkyloxycarbonyl; C1-6alkyl substituted with formyl, C1-6alkylearbonyl, C1-­6alkyloxycarbonyl, C1-6alkylcarbonyloxy; or C1-6alkyloxyC1-6alkylcarbonyl optionally substituted with C1-6alkyloxycarbonyl; X represents a direct bond; -(CH2)n3­or -(CH2)m4-X1a-X1b-; R2 represents C3-7cycloalkyl; phenyl; a 4, 5, 6- or 7-membered monocyclic heterocycle containing at least one heteroatom. selected from 0, S or N; benzoxazolyl or a radical of formula (a-1), wherein said R2 substituent may optionally be substituted; R3 represents halo; hydroxy; optionally substituted C1-.6alkyl; C2-6a]kenyl or C2-6alkynyl, each optionally substituted; optionally substituted polyhaloC1-6alkyl; optionally substituted C1-6alkyloxy; optionally substituted polyhaloC1-­6alkyloxy; C1-6alkylthio; polyhaloC1-6a]kylthio; C1-6a]kyloxycarbonyl; C1-6alkylcarbonyloxy; C1-6alkylearbonyl; polyhaloC1-6alkylcarbonyl; cyano; carboxyl; aryloxy; arylthio; arylcarbonyl; NR6b R7b; C(=O)-NR 6b R 7b; -NR5-C(=O)R5;'-S(=O)nl-R8a; -NR5S(=O)nl -R 8a;-NR 5 -S(=O)nl -R 8a ; -S-CN; -NR5 -CN;R4 represents hydrogen; halo; hydroxy; optionally substituted C1-4alkyl; C2-4alkenyl or C2-4alkynyl, each optionally substituted; polyha]oC1-3alkyl; optionally substituted C1-4alkyloxy; polyhalo-C1-3alkyloxy; C1-4alkylthio; polyhaloC1-3alkylthio­ C1-4alkyloxycarbonyl; C1-4alkylcarbonyloxy; C1-4alkylcarbonyl; polyhatoC1-4alkyl­carbonyl; nitro; cyano; carboxyl; NR10 R11; C(=O)NR10-R11;NR5-C(=O)-NR10R11;-NR5 -C(=O)-R5; -S(=O)nl,-R12 -NR5-S(=O)nI-R12 ; -S-CN; -NR5 -CN; their use, pharmaceutical compositions comprising them and processes for their preparation.

  这项发明涉及式(I)的化合物，一种N-氧化物，一种药用可接受的加合盐，一种季铵盐和其立体化学异构体形式，其中环A代表苯基、吡啶基、嘧啶基、吡啶并嘧啶基或吡嗪基；R1代表氢；芳基；甲酰基；Cl.6烷基羰基，C1-6烷基；C1-6烷氧羰基；C1-6烷基取代的甲酰基，C1-6烷基羰基，C1-6烷氧羰基，C1-6烷基羰氧基；或C1-6烷氧基C1-6烷基羰基，可选地取代C1-6烷氧羰基；X代表直链键；-(CH2)n3或-(CH2)m4-X1a-X1b-；R2代表C3-7环烷基；苯基；含有至少一个杂原子的4,5,6-或7-成员单环杂环烃，所述杂原子选自O、S或N；苯并噁唑基或式(a-1)的基团，其中所述R2取代基可选择地被取代；R3代表卤素；羟基；可选地取代的C1-6烷基；C2-6烯基或C2-6炔基，每种可选择地被取代；可选择地取代的多卤C1-6烷基；可选择地取代的C1-6烷氧基；可选择地取代的多卤C1-6烷氧基；C1-6烷基硫；多卤C1-6烷基硫；C1-6烷氧羰基；C1-6烷基羰氧基；C1-6烷氧羰基；多卤C1-6烷基羰基；氰基；羧基；芳基氧基；芳基硫；芳基羰基；NR6b R7b；C(=O)-NR 6b R 7b；-NR5-C(=O)R5；'-S(=O)nl-R8a；-NR5S(=O)nl -R 8a；-NR 5 -S(=O)nl -R 8a；-S-CN；-NR5 -CN；R4代表氢；卤素；羟基；可选地取代的C1-4烷基；C2-4烯基或C2-4炔基，每种可选择地被取代；多卤C1-3烷基；可选地取代的C1-4烷氧基；多卤C1-3烷氧基；C1-4烷基硫；多卤C1-3烷基硫；C1-4烷氧羰基；C1-4烷基羰氧基；C1-4烷基羰基；多卤C1-4烷基羰基；硝基；氰基；羧基；NR10 R11；C(=O)NR10-R11；NR5-C(=O)-NR10R11；-NR5 -C(=O)-R5；-S(=O)nl,-R12 -NR5-S(=O)nI-R12；-S-CN；-NR5 -CN；它们的使用，包括它们的药用组合物和其制备方法。
• TRIAZOLOPYRIMIDINE DERIVATIVES AS GLYCOGEN SYNTHASE KINASE 3 INHIBITORS
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1658292B1

  公开（公告）日：2007-08-15
• Triazolopyrimidine Derivatives As Glycogen Synthase Kinase 3 Inhibitors
  申请人：Edgard Eddy Jean

  公开号：US20090036471A1

  公开（公告）日：2009-02-05

  This invention concerns compounds of formula N-oxides, pharmaceutically acceptable addition salts, quaternary amines and stereochemically isomeric forms thereof, their use, pharmaceutical compositions comprising them, processes for their preparation, and methods of their use.
• US7560458B2
  申请人：——

  公开号：US7560458B2

  公开（公告）日：2009-07-14
• Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization
  作者：Heng Zhang、Ye Tian、Dongwei Kang、Zhipeng Huo、Zhongxia Zhou、Huiqing Liu、Erik De Clercq、Christophe Pannecouque、Peng Zhan、Xinyong Liu

  DOI：10.1016/j.ejmech.2017.02.047

  日期：2017.4

  A novel series of uracil-bearing DAPYs derivatives were designed and synthesized via structure-based molecular hybridization to discover compounds with improved anti-resistance profiles. Anti-HIV activity of the designed compounds was tested in MT-4 cell cultures. The most promising compound 16d showed excellent activity with EC50 value of 5.6 nM against wide-type HIV-1 and low cytotoxicity (SI > 50000). Activity against the clinic prevalent mutant strains was also tested, suggesting that 16d was sensitive to E138K (EC50 = 34.2 nM). Primary drug-like properties, such as water solubility and logP, were evaluated by experiment or calculation, which indicated that introducing an uracil can improve solubility. The molecular modeling accompanied with the preliminary SAR correlations paved the way for the next round of rational design of potent anti-HIV agents. (C) 2017 Elsevier Masson SAS. All rights reserved.