2,4-diamino-5-phenylthioquinazoline | 123241-99-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2,4-diamino-5-phenylthioquinazoline
• 英文别名: 5-Phenylsulfanyl-2,4-quinazolinediamine；5-phenylsulfanylquinazoline-2,4-diamine
• CAS: 123241-99-6
• 化学式: C₁₄H₁₂N₄S
• 分子量: 268.342
• InChiKey: BUFDQCGCADQQQY-UHFFFAOYSA-N

物化性质

• 沸点：
  576.0±58.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,4-diamino-5-phenylthioquinazoline 在 potassium permanganate 作用下， 以 水 、 溶剂黄146 为溶剂， 以60%的产率得到5-Benzenesulfonyl-quinazoline-2,4-diamine
  参考文献：
  名称：

  5-取代的2,4-二氨基喹唑啉的抗叶酸和抗菌活性。

  摘要：

  合成了一系列5-取代的2,4-二氨基喹唑啉（3），并从细菌和哺乳动物来源评估了它们作为二氢叶酸还原酶（DHFR）的抑制剂。最好的化合物（例如53种）对大肠杆菌DHFR表现出良好的活性，但对细菌的选择性没有比哺乳动物酶高的选择性。抑制酶的构效关系似乎很复杂，不宜进行简单分析。提出了一个假设来解释观察到的定性结构-活性关系。该化合物对体外完整细菌细胞生长的抑制活性与抑制分离的细菌酶的抑制活性非常相似，这表明它们的抗叶酸作用是其抗菌作用的原因。

  DOI：

  10.1021/jm00163a067
• 作为产物：
  描述：

  2,6-二硝基氯苯 在 盐酸 、 potassium carbonate 、 tin(ll) chloride 作用下， 以 二乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 2,4-diamino-5-phenylthioquinazoline
  参考文献：
  名称：

  5-取代的2,4-二氨基喹唑啉的抗叶酸和抗菌活性。

  摘要：

  合成了一系列5-取代的2,4-二氨基喹唑啉（3），并从细菌和哺乳动物来源评估了它们作为二氢叶酸还原酶（DHFR）的抑制剂。最好的化合物（例如53种）对大肠杆菌DHFR表现出良好的活性，但对细菌的选择性没有比哺乳动物酶高的选择性。抑制酶的构效关系似乎很复杂，不宜进行简单分析。提出了一个假设来解释观察到的定性结构-活性关系。该化合物对体外完整细菌细胞生长的抑制活性与抑制分离的细菌酶的抑制活性非常相似，这表明它们的抗叶酸作用是其抗菌作用的原因。

  DOI：

  10.1021/jm00163a067

文献信息

• Formulations for hydrophobic pharmaceutical agents
  申请人：——

  公开号：US20010012844A1

  公开（公告）日：2001-08-09

  The present invention features formulations, including liquid, semi-solid or solid pharmaceutical formulations, that improve the oral bioavailability of hydrophobic pharmaceutical agents, such as quinazoline-, nitrothiazole-, and indolinone-based compounds. Also featured are formulations for parenteral delivery of such hydrophobic pharmaceutical agents, as well as methods of making and using both types of formulations.

  本发明涉及包括液体、半固体或固体制剂的配方，可以提高疏水性药物，如喹唑啉、硝基噻唑和吲哚酮类化合物的口服生物利用度。还包括适用于静脉注射递送这些疏水性药物的配方，以及制备和使用这两种类型配方的方法。
• Methods of modulating serine/threonine protein kinase function with quinazoline-based compounds
  申请人：——

  公开号：US20010014679A1

  公开（公告）日：2001-08-16

  The present invention is directed in part towards methods of modulating the function of serine/threonine protein kinases with quinazoline-based compounds. The methods incorporate cells that express a serine/threonine protein kinase, such as RAF. In addition, the invention describes methods of preventing and treating serine/threonine protein kinase-related abnormal conditions in organisms with a compound identified by the invention. Furthermore, the invention pertains to quinazoline compounds and pharmaceutical compositions comprising these compounds.

  本发明部分涉及使用基于喹唑啉的化合物调节丝氨酸/苏氨酸蛋白激酶功能的方法。该方法包括表达丝氨酸/苏氨酸蛋白激酶（例如RAF）的细胞。此外，本发明还描述了使用本发明所确定的化合物预防和治疗有关丝氨酸/苏氨酸蛋白激酶的异常情况的方法。此外，本发明还涉及喹唑啉化合物和包含这些化合物的制药组合物。
• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• Selective Inhibitors of Candida albicans Dihydrofolate Reductase: Activity and Selectivity of 5-(Arylthio)-2,4-diaminoquinazolines
  作者：Joseph H. Chan、Jean S. Hong、Lee F. Kuyper、David P. Baccanari、Suzanne S. Joyner、Robert L. Tansik、Christine M. Boytos、Sharon K. Rudolph

  DOI：10.1021/jm00018a021

  日期：1995.9

  The recent increase in fungal infections, especially among AIDS patients, has resulted in the need for more effective antifungal agents. In our search for such agents, we focused on developing compounds which inhibit fungal dihydrofolate reductase (DHFR). A series of 25 5-(arylthio)-2,4-diaminoquinazolines were synthesized as potentially selective inhibitors of Candida albicans DHFR. The majority of the compounds were potent inhibitors of C. albicans DHFR and much less active against human DHFR. High selectivity, as defined by the ratio of the I-50 values for human and C. albicans DHFR, was achieved by compounds with bulky and rigid 4-substituents in the phenylthio moiety. For example, 5-[(4-morpholinophenyl)thio]-2,4-diaminoquinazoline displayed a selectivity ratio of 540 and was the most selective inhibitor synthesized to date. Substitution in the 2- or 3-position of the 5-phenylthio group provided only marginal selectivity. 6-Substituted-5-[(4-tert-butylphenyl)thio]-2,4-diaminoquinazolines showed potent activity against the C. albicans enzyme but were equally active against human DHFR. Most of the selective compounds were also good inhibitors of C. albicans cell growth, with minimum inhibitory concentration values as low as 0.05 mu g/mL.
• METHODS OF MODULATING SERINE/THREONINE PROTEIN KINASE FUNCTION WITH QUINAZOLINE-BASED COMPOUNDS
  申请人：Sugen, Inc.

  公开号：EP0981519A1

  公开（公告）日：2000-03-01