N⁴-(4-methylbenzyl)-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine | 1196993-88-0

• 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: N⁴-(4-methylbenzyl)-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine
• 英文别名: ST-994；N4-(4-Methylbenzyl)-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine；4-N-[(4-methylphenyl)methyl]-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine
• CAS: 1196993-88-0
• 化学式: C₁₇H₂₄N₆
• 分子量: 312.418
• InChiKey: PJVXROVDPIVILM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  70.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-甲基哌嗪 、 6-Chloro-4-N-[(4-Methylphenyl)methyl]pyrimidine-2,4-Diamine 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 生成 N⁴-(4-methylbenzyl)-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  2,4-Diaminopyrimidines as histamine H4 receptor ligands—Scaffold optimization and pharmacological characterization

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2009.08.059

文献信息

• HISTAMINE 4 RECEPTOR PARTIAL AGONISTS, INVERSE AGONISTS OR ANTAGONISTS FOR USE IN TREATING CHRONIC UVEITIS
  申请人：UCL Business Plc.

  公开号：EP2890373B1

  公开（公告）日：2017-11-08
• HISTAMINE 4 RECEPTOR PARTIAL AGONISTS, INVERSE AGONISTS OR ANTAGONISTS FOR USE IN TREATING NON-AUTOIMMUNE UVEITIS
  申请人：UCL BUSINESS PLC

  公开号：US20150209348A1

  公开（公告）日：2015-07-30

  The invention provides a compound which is a histamine 4 receptor antagonist, partial agonist or inverse agonist, for use in the treatment of non-autoimmune uveitis. The compound preferably has a structural core comprising a substituted pyrimidine group, such as an aminopyrimidine, diaminopyrimidine or triaminopyrimidine group, a thienopyrimidine, a furopyrimidine, a benzimidazole, an aryl or heteroaryl-fused pyrimidine, an indole, a bicyclic heteroaryl-substituted imidazole or a quinazoline group.
• US9579318B2
  申请人：——

  公开号：US9579318B2

  公开（公告）日：2017-02-28
• [EN] HISTAMINE 4 RECEPTOR PARTIAL AGONISTS, INVERSE AGONISTS OR ANTAGONISTS FOR USE|IN TREATING NON-AUTOIMMUNE UVEITIS<br/>[FR] AGONISTES PARTIELS, AGONISTES INVERSES OU ANTAGONISTES DU RÉCEPTEUR DE L'HISTAMINE 4 DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE L'UVÉITE NON AUTO-IMMUNE
  申请人：UCL BUSINESS PLC

  公开号：WO2014033480A1

  公开（公告）日：2014-03-06

  The invention provides a compound which is a histamine 4 receptor antagonist, partial agonist or inverse agonist, for use in the treatment of non-autoimmune uveitis. The compound preferably has a structural core comprising a substituted pyrimidine group, such as an aminopyrimidine, diaminopyrimidine or triaminopyrimidine group, a thienopyrimidine, a furopyrimidine, a benzimidazole, an aryl or heteroaryl-fused pyrimidine, an indole, a bicyclic heteroaryl-substituted imidazole or a quinazoline group.
• 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.