5-Phenethylpyrimidine-2,4-diamine

• 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: 5-Phenethylpyrimidine-2,4-diamine
• 英文别名: 5-(2-phenylethyl)pyrimidine-2,4-diamine
• 化学式: C₁₂H₁₄N₄
• 分子量: 214.27
• InChiKey: BEESSKJNILHXMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,4-二氨基嘧啶-5-甲醛 在 甲醇 、 氢氧化钾 、 1,5-二氮杂双环[4.3.0]壬-5-烯 、 氢气 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 100.0 ℃ 、150.0 kPa 条件下， 反应 16.5h， 生成 5-Phenethylpyrimidine-2,4-diamine
  参考文献：
  名称：

  Folate-Synthesizing Enzyme System as Target for Development of Inhibitors and Inhibitor Combinations against Candida albicansSynthesis and Biological Activity of New 2,4-Diaminopyrimidines and 4‘-Substituted 4-Aminodiphenyl Sulfones

  摘要：

  The paper describes the design, synthesis, and testing of inhibitors of folate-synthesizing enzymes and of whole cell cultures of Candida albicans. The target enzymes used were dihydropteroic acid synthase (SYN) and dihydrofolate reductase (DHFR). Several series of new 2,4-diaminopyrimidines were synthesized and tested as inhibitors of DHFR and compared with their activity against DHFR derived from mycobacteria and Escherichia coli. To test for selectivity, also rat DHFR was used. A series of substituted 4-aminodiphenyl sulfones was tested for inhibitory activity against SYN and the I-50 values compared to those obtained previously against Plasmodium berghei- and E. coli-derived SYN. Surprisingly, QSAR equations show very similar structural dependencies. To find an explanation for the large difference in the I-50 values observed for enzyme inhibition (SYN, DHFR) and for inhibition of cell cultures of Candida, mutant strains with overexpressed efflux pumps and strains in which such pumps are deleted were included in the study and the MICs compared. Efflux pumps were responsible for the low activity of some of the tested derivatives, others showed no increase in activity after pumps were knocked out. In this case it may be speculated that these derivatives are not able to enter the cells.

  DOI：

  10.1021/jm030931w

文献信息

• CHEMICAL COMPOUNDS
  申请人：Axten Jeffrey Michael

  公开号：US20110275611A1

  公开（公告）日：2011-11-10

  The invention is directed to 6-(4-pyrimidinyl)-1H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R 1 -R 4 are defined herein. The compounds of the invention axe inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention

  本发明涉及6-(4-嘧啶基)-1H-吲唑衍生物。具体而言，本发明涉及公式（I）中R1-R4所定义的化合物。本发明的化合物是PDK1的抑制剂，可用于治疗免疫和代谢性疾病和障碍，这些疾病和障碍以恒定激活的ACG激酶为特征，例如乳腺、结肠和肺癌等。因此，本发明还涉及包含本发明化合物的制药组合物。本发明还涉及使用本发明化合物或包含本发明化合物的制药组合物抑制PDK1活性和治疗相关障碍的方法。
• PYRIMIDINE, PYRIDINE, PTERIDINONE AND INDAZOLE DERIVATIVES AS ENZYME INHIBITORS
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0674627A1

  公开（公告）日：1995-10-04
• 5-HT 7 RECEPTOR ANTAGONISTS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1280781B1

  公开（公告）日：2009-11-18
• DIAMINOPYRIMIDINES AS P2X3 AND P2X2/3 ANTAGONISTS
  申请人：Roche Palo Alto LLC

  公开号：US20170096404A1

  公开（公告）日：2017-04-06

  Compounds and methods for treating diseases mediated by a P2X 3 and/or a P2X 2/3 receptor antagonist, the methods comprising administering to a subject in need thereof an effective amount of a compound of formula (I): or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein X is O, D, Y, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as defined herein.
• [EN] PYRIMIDINE, PYRIDINE, PTERIDINONE AND INDAZOLE DERIVATIVES AS ENZYME INHIBITORS<br/>[FR] DERIVES DE PYRIMIDINE, DE PYRIDINE, DE PTERIDINONE ET D'INDAZOLE UTILISES COMME INHIBITEURS ENZYMATIQUES
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：WO1994014780A1

  公开（公告）日：1994-07-07

  (EN) The use of a compound which binds at the tetrahydrobiopterin site of NO synthase for the treatment of conditions where there is an advantage in inhibiting neuronal NO synthase with little or no inhibition of endothelial NO synthase is disclosed. Pharmaceutical formulations comprising such compounds, and processes, including a novel process, for their preparation are also disclosed.(FR) L'invention concerne l'utilisation d'un composé qui se lie au site de tétrahydrobioptérine de la NO synthétase pour le traitement d'états dans lesquels il est bénéfique d'inhiber la NO synthétase neuronale avec peu ou pas d'inhibition de la NO synthétase endothéliale. L'invention concerne également des formulations pharmaceutiques contenant de tels composés et des procédés, y compris un nouveau procédé, pour leur préparation.