4-(4-bromophenyl)-6-(3,4,5-trimethoxyphenyl)pyrimidin-2-amine | 666827-69-6

• 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-(4-bromophenyl)-6-(3,4,5-trimethoxyphenyl)pyrimidin-2-amine
• 英文别名: 4-(4-Bromophenyl)-6-(3,4,5-trimethoxyphenyl)pyrimidin-2-amine
• CAS: 666827-69-6
• 化学式: C₁₉H₁₈BrN₃O₃
• 分子量: 416.274
• InChiKey: IJBAMVNXGVZYBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  79.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-溴苯乙酮 在 sodium hydride 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 4-(4-bromophenyl)-6-(3,4,5-trimethoxyphenyl)pyrimidin-2-amine
  参考文献：
  名称：

  Synthesis and biological evaluation of substituted 4,6-diarylpyrimidines and 3,5-diphenyl-4,5-dihydro-1H-pyrazoles as anti-tubercular agents

  摘要：

  Various substituted 4,6-diarylpyrimidin-2-amine (4), 4,6-diaryl-2-(heteroaryl)pyrimidine (6) and 1-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)ethanone (7) derivatives were synthesized in good yields using simple methodology. The synthesized compounds (4-7) were evaluated for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. Compounds 4a, 6b, 7b, and 7c exhibited significant anti-tubercular activity at MIC values 25, 25, 12.5 and 12.5 mu M concentration. In vitro cytotoxicity data using non cancerous hepatic monocytes (THP-1) cells indicated that most active compounds 7b and 7c were safe as their MIC values were much lower than their cytotoxic values. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.094

文献信息

• Design, synthesis and biological evaluation of novel pyrimidine derivatives as bone anabolic agents promoting osteogenesis via the BMP2/SMAD1 signaling pathway
  作者：Sumit K. Rastogi、Sonu Khanka、Santosh Kumar、Amardeep Lakra、Rajat Rathur、Kriti Sharma、Amol Chhatrapati Bisen、Rabi Sankar Bhatta、Ravindra Kumar、Divya Singh、Arun K. Sinha

  DOI：10.1039/d3md00500c

  日期：——

  [PTH (1–34)] is an effective anabolic therapy, long-term repeated subcutaneous administration is not recommended. Henceforth, orally bio-available small-molecule-based novel therapeutics are unmet medical needs to improve the treatment. In this study, we designed, synthesized, and carried out a biological evaluation of 31 pyrimidine derivatives as potent bone anabolic agents. A series of in vitro experiments

  双膦酸盐等抗再吸收抑制剂被广泛使用，但其疗效有限且副作用严重。虽然皮下注射特立帕肽[PTH (1-34)]是一种有效的合成代谢疗法，但不建议长期重复皮下注射。今后，口服生物可利用的基于小分子的新型疗法是改善治疗的未满足的医疗需求。在这项研究中，我们设计、合成了 31 种嘧啶衍生物作为有效的骨合成代谢剂，并对其进行了生物学评价。一系列体外实验证实N- (5-溴-4-(4-溴苯基)-6-(2,4,5-三甲氧基苯基)嘧啶-2-基)己酰胺 ( 18a ) 是最有效的合成代谢剂下午 1 点。它通过激活 BMP2/SMAD1 信号通路上调成骨基因（RUNX2 和 1 型 col）的表达来促进成骨。使用体内骨折缺陷模型进一步验证了体外成骨潜力，其中化合物18a在5 mg kg -1下促进骨形成速率。我们还建立了18a的构效关系和药代动力学研究。