6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine | 4940-96-9

• 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: 6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine
• 英文别名: 6-(4-methyl-piperazin-1-yl)-pyrimidine-2,4-diamine；2,4-Diamino-6-(4-methylpiperazino)pyrimidine；2,5-Diamino-6-(4-methyl-piperazino)-pyrimidin
• CAS: 4940-96-9
• 化学式: C₉H₁₆N₆
• 分子量: 208.266
• InChiKey: RBHNSRTVBDSNLG-UHFFFAOYSA-N

物化性质

• 熔点：
  224-225 °C
• 沸点：
  492.4±55.0 °C(Predicted)
• 密度：
  1.271±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  84.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  对苯醌 、 6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine 在 溶剂黄146 作用下， 反应 6.0h， 以43%的产率得到2-Amino-4-(4-methyl-piperazin-1-yl)-9H-pyrimido[4,5-b]indol-6-ol
  参考文献：
  名称：

  2,4-二氨基-9H-嘧啶[4,5-b]吲哚-5-醇：合成，体外细胞毒性活性和QSAR研究。

  摘要：

  合成了一系列新颖的2,4-二氨基嘧啶[4,5-b]吲哚6-醇，并针对四种源自实体瘤的人类癌细胞系评估了体外细胞毒活性。当在嘧啶并[4，5-b]吲哚系统的g侧上环杂芳环时，观察到活性增加，从而得到具有与玫瑰树碱和顺铂相当的活性的化合物。为了了解实验性细胞毒性活性，进行了QSAR研究，结果表明实验性IC和预测IC之间具有很好的线性关系（50）。

  DOI：

  10.1016/j.bmc.2006.06.051
• 作为产物：
  描述：

  N-甲基哌嗪 、 2,4-二氨基-6-氯嘧啶 在 水 作用下， 反应 4.0h， 以83%的产率得到6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Synthesis and evaluation of novel ligands for the histamine H4 receptor based on a pyrrolo[2,3-d]pyrimidine scaffold

  摘要：

  Starting from a known H4R ligand based on a pyrimidine skeleton, a series of novel analogues based on a pyrrolo[2,3-d]pyrimidine scaffold have been prepared. Whereas the original pyrimidine congener shows good affinity at hH(4)R (K-i = 0.5 mu M), its lacks selectivity with a K-i value for the hH(3)R of 1 mu M. Within the newly synthesized pyrrolo[2,3-d]pyrimidines, several congeners show K-i values of less than 1 mu M at the hH(4)R and show a much improved selectivity profile. Therefore, these series represent an interesting starting point for the discovery of novel hH(4)R ligands. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.139

文献信息

• Method for Pain Treatment
  申请人：Cowart Marlon D.

  公开号：US20080194538A1

  公开（公告）日：2008-08-14

  This invention discloses a method of treating pain by administering histamine H 4 receptor ligands and compositions comprising the same.

  这项发明揭示了一种通过给予组织胺H4受体配体和包含相同的组合物来治疗疼痛的方法。
• Novel pyrimidine compounds
  申请人：Toyo Boseki Kabushiki Kaisha

  公开号：EP0243817A1

  公开（公告）日：1987-11-04

  Novel pyrimidine compounds of the formula: wherein R₁ and R₁ʹ are each hydrogen atom, a lower alkyl, benzyl, an alkali metal, or ammonium; R₂ is hydrogen atom, a halogen atom, a lower alkyl, a lower alkoxy, an aryl, a group of the formula: (wherein R₃ and R₄ are each hydrogen atom, a lower alkyl, or an aryl), or a group of the formula: [wherein R₅ and R₆ are each an alkylene having 1 to 3 carbon atoms, and X is oxygen atom, methylene, or a group of the formula: (wherein Y is hydrogen atom, a lower alkyl, benzyl, or an aryl)], which have excellent antiallergic activities and are useful for the prophylaxis and treatment of various allergic diseases, and a pharmaceutical composition containing said pyrimidine compound as an active ingredient.

  式中的新型嘧啶化合物： 其中R₁和R₁ʹ各自是氢原子、低级烷基、苄基、碱金属或铵；R₂是氢原子、卤素原子、低级烷基、低级烷氧基、芳基、式中的基团： (其中 R₃ 和 R₄ 各为氢原子、低级烷基或芳基）或式中的基团： [其中 R₅ 和 R₆ 各为具有 1 至 3 个碳原子的亚烷基，X 为氧原子、亚甲基或式中的基团： (其中 Y 为氢原子、低级烷基、苄基或芳基）]，它们具有优异的抗过敏活性，可用于预防和治疗各种过敏性疾病，以及一种含有所述嘧啶化合物作为活性成分的药物组合物。
• Structure−Activity Studies on a Series of a 2-Aminopyrimidine-Containing Histamine H₄ Receptor Ligands
  作者：Robert J. Altenbach、Ronald M. Adair、Brian M. Bettencourt、Lawrence A. Black、Shannon R. Fix-Stenzel、Sujatha M. Gopalakrishnan、Gin C. Hsieh、Huaqing Liu、Kennan C. Marsh、Michael J. McPherson、Ivan Milicic、Thomas R. Miller、Timothy A. Vortherms、Usha Warrior、Jill M. Wetter、Neil Wishart、David G. Witte、Prisca Honore、Timothy A. Esbenshade、Arthur A. Hancock、Jorge D. Brioni、Marlon D. Cowart

  DOI：10.1021/jm8005959

  日期：2008.10.23

  A series of 2-aminopyrimidines was synthesized as ligands of the histamine H-4 receptor (H4R). Working in part from a pyrimidine hit that was identified in an HTS campaign, SAR studies were carried out to optimize the potency, which led to compound 3,4-tert-butyl-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylamine. We further studied this compound by systematically modifying the core pyrimidine moiety, the methylpiperazine at position 4, the NH2 at position 2, and positions 5 and 6 of the pyrimidine ring. The pyrimidine 6 position benefited the most from this optimization, especially in analogs in which the 6-tert-butyl was replaced with aromatic and secondary amine moieties. The highlight of the optimization campaign was compound 4, 4-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]benzonitrile, which was potent in vitro and was active as an anti-inflammatory agent in an animal model and had antinociceptive activity in a pain model, which supports the potential of H4R antagonists in pain.
• 2,4-Diaminopyrimidines as histamine H4 receptor ligands—Scaffold optimization and pharmacological characterization
  作者：Kerstin Sander、Tim Kottke、Yusuf Tanrikulu、Ewgenij Proschak、Lilia Weizel、Erich H. Schneider、Roland Seifert、Gisbert Schneider、Holger Stark

  DOI：10.1016/j.bmc.2009.08.059

  日期：2009.10

  The human histamine H-4 receptor (hH(4)R) is a promising new target in the therapy of inflammatory diseases and disorders of the immune system. For the development of new H4R antagonists a broad ligand-based virtual screening was performed resulting in two hits. The dissection of their common annelated aromatic core into its heteromonocyclic components showed that 2,4-diaminopyrimidine is a potent hH(4)R affinity scaffold, which was comprehensively investigated. Structure-activity relationship studies revealed that slight structural changes evoke extensive differences in functional activities and potencies: while o-and p-substituted benzyl amines mainly showed partial agonism, m-substituted and rigidified ones exhibited inverse agonist efficacy. (C) 2009 Elsevier Ltd. All rights reserved.
• US4729995
  申请人：——

  公开号：——

  公开（公告）日：——