6-anilinomethyl-quinazoline-2,4-diamine | 27133-39-7

• 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: 6-anilinomethyl-quinazoline-2,4-diamine
• 英文别名: 2,4-Diamino-6-anilinomethylchinazolin；6-(Anilinomethyl)quinazoline-2,4-diamine
• CAS: 27133-39-7
• 化学式: C₁₅H₁₅N₅
• 分子量: 265.318
• InChiKey: SQHNSLWKFCXHKZ-UHFFFAOYSA-N

物化性质

• 熔点：
  196-198 °C
• 沸点：
  579.4±60.0 °C(Predicted)
• 密度：
  1.362±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  89.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 6-anilinomethyl-quinazoline-2,4-diamine 在 盐酸 、 sodium cyanoborohydride 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以89%的产率得到6-[(N-methylanilino)methyl]quinazoline-2,4-diamine
  参考文献：
  名称：

  设计，合成，计算预测和生物学评估酯类软药物，作为卡氏肺孢子虫中二氢叶酸还原酶的抑制剂。

  摘要：

  已经设计，合成和评估了一系列与非经典二氢叶酸还原酶（DHFR）抑制剂曲美曲塞和匹瑞特昔姆相关的亲脂性软药物，并在DHFR分析中进行了评估，其中特别强调了对卡氏假单胞菌DHFR的抑制作用。最好的抑制剂在连接两个芳族系统的桥中包含一个酯键，其效价比曲美曲酯和派立特新的效价低约10倍。代谢物被设计为弱抑制剂。此外，为了更好地理解决定选择性的因素，对卡氏肺孢子虫和人酶中的三个配体与DHFR进行了分子动力学模拟。使用线性相互作用能法可以正确地确定DHFR的相对抑制率。软性药物旨在用于当地管理。选择了一种代表性的酯用于大鼠的药代动力学研究，发现该酯能快速代谢降解成预期的无活性代谢物。

  DOI：

  10.1021/jm010856u
• 作为产物：
  描述：

  苯胺 、 2,4-diamino-6-quinazoline-6-carbonitrile 在 镍 氢气 作用下， 反应 20.0h， 以52%的产率得到6-anilinomethyl-quinazoline-2,4-diamine
  参考文献：
  名称：

  设计，合成，计算预测和生物学评估酯类软药物，作为卡氏肺孢子虫中二氢叶酸还原酶的抑制剂。

  摘要：

  已经设计，合成和评估了一系列与非经典二氢叶酸还原酶（DHFR）抑制剂曲美曲塞和匹瑞特昔姆相关的亲脂性软药物，并在DHFR分析中进行了评估，其中特别强调了对卡氏假单胞菌DHFR的抑制作用。最好的抑制剂在连接两个芳族系统的桥中包含一个酯键，其效价比曲美曲酯和派立特新的效价低约10倍。代谢物被设计为弱抑制剂。此外，为了更好地理解决定选择性的因素，对卡氏肺孢子虫和人酶中的三个配体与DHFR进行了分子动力学模拟。使用线性相互作用能法可以正确地确定DHFR的相对抑制率。软性药物旨在用于当地管理。选择了一种代表性的酯用于大鼠的药代动力学研究，发现该酯能快速代谢降解成预期的无活性代谢物。

  DOI：

  10.1021/jm010856u

文献信息

• Novel pyrimidine derivatives and methods of making and using these derivatives
  申请人：——

  公开号：US20020052384A1

  公开（公告）日：2002-05-02

  This invention discloses pyrimidine derivatives, and pharmaceutically acceptable salts and prodrugs thereof, useful in therapeutically and/or prophylactically treating patients with an illness. Such illnesses include cancer, and secondary infections caused by Pneumocystis carinii and Toxoplasmosis gondii in immunocompromised patients. The compounds themselves, methods of making these compounds, and methods of using these compounds are all disclosed.

  本发明披露了嘧啶衍生物及其药学上可接受的盐和前药，用于治疗患有疾病的患者的治疗和/或预防。这种疾病包括癌症和免疫功能受损的患者因肺孢子菌和弓形虫感染而引起的继发感染。本发明披露了这些化合物本身，制备这些化合物的方法以及使用这些化合物的方法。
• Pyrimidine derivatives and methods of making and using these derivatives
  申请人：——

  公开号：US20030144509A1

  公开（公告）日：2003-07-31

  This invention discloses compounds, and pharmaceutically acceptable salts thereof, useful in therapeutically and/or prophylactically treating patients with an illness. Such illnesses include cancer, and secondary infections caused by Pneumocystis carinii and Toxoplasmosis gondii in immunocompromised patients. The compounds themselves, methods of making these compounds, and methods of using these compounds are all disclosed.

  本发明揭示了化合物及其药学上可接受的盐，用于治疗或预防患有疾病的患者。这些疾病包括癌症，以及免疫功能受损患者中由肺孢子菌和弓形虫引起的继发感染。本发明还揭示了这些化合物本身，制备这些化合物的方法以及使用这些化合物的方法。
• New small-molecule inhibitors of dihydrofolate reductase inhibit Streptococcus mutans
  作者：Qiong Zhang、Thao Nguyen、Megan McMichael、Sadanandan E. Velu、Jing Zou、Xuedong Zhou、Hui Wu

  DOI：10.1016/j.ijantimicag.2015.03.015

  日期：2015.8

  Streptococcus mutans is a major aetiological agent of dental caries. Formation of biofilms is a key virulence factor of S. mutans. Drugs that inhibit S. mutans biofilms may have therapeutic potential. Dihydrofolate reductase (DHFR) plays a critical role in regulating the metabolism of folate. DHFR inhibitors are thus potent drugs and have been explored as anticancer and antimicrobial agents. In this study, a library of analogues based on a DHFR inhibitor, trimetrexate (TMQ), an FDA-approved drug, was screened and three new analogues that selectively inhibited S. mutans were identified. The most potent inhibitor had a 50% inhibitory concentration (IC50) of 454.0 +/- 10.2 nM for the biofilm and 8.7 +/- 1.9 nM for DHFR of S. mutans. In contrast, the IC50 of this compound for human DHFR was ca. 1000 nM, a > 100-fold decrease in its potency, demonstrating the high selectivity of the analogue. An analogue that exhibited the least potency for the S. mutans biofilm also had the lowest activity towards inhibiting S. mutans DHFR, further indicating that inhibition of biofilms is related to reduced DHFR activity. These data, along with docking of the most potent analogue to the modelled DHFR structure, suggested that the TMQ analogues indeed selectively inhibited S. mutans through targeting DHFR. These potent and selective small molecules are thus promising lead compounds to develop new effective therapeutics to prevent and treat dental caries. (C) 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
• METHODS OF PREPARATION AND RESOLUTION OF E/Z ISOMERS OF VINYLFURO[2,3-D]PYRIMIDINE AND THEIR BIOLOGICAL ACTIVITIES AND RELATED COMPOSITIONS AND METHODS OF TREATMENT
  申请人：Gangjee Aleem

  公开号：US20070238742A1

  公开（公告）日：2007-10-11

  Stereoselective methods for preparing the individual isomers, E- and Z-2,4-substituted-5-vinylfuro[2,3-d]pyrimidine and pharmaceutically acceptable salts, solvates, and prodrugs thereof using selective synthetic conditions are provided. This class of pyrimidine compounds function as receptor tyrosine kinase inhibitors during angiogenesis and resists the development of new blood vessels in tumors as well as inhibit the folate pathway required for cell growth. The isomers of these compounds are separated by physical, chromatographic, and/or HPLC methods. Their biological activities are described. Also provided are methods of treating diseases associated with angiogenesis in a patient comprising administering the isolated E- and Z-isomers of the composition of the present invention.
• US5346900A
  申请人：——

  公开号：US5346900A

  公开（公告）日：1994-09-13