N-(6-Fluoro-4-methyl-quinazolin-2-yl)-guanidine | 1449242-43-6

• 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: N-(6-Fluoro-4-methyl-quinazolin-2-yl)-guanidine
• 英文别名: 1-(6-fluoro-4-methylquinazolin-2-yl)guanidine；2-(6-Fluoro-4-methylquinazolin-2-yl)guanidine；2-(6-fluoro-4-methylquinazolin-2-yl)guanidine
• CAS: 1449242-43-6
• 化学式: C₁₀H₁₀FN₅
• 分子量: 219.221
• InChiKey: ZRANMLRZCWTDDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(6-Fluoro-4-methyl-quinazolin-2-yl)-guanidine 、 巴氯芬杂质9 在 六氟异丙醇 、 碳酸氢钠 作用下， 反应 16.0h， 生成 ethyl 4-(4-chlorophenyl)-2-(6-fluoro-4-methylquinazolin-2-ylamino)-6-methyl-1,4-dihydropyrimidine-5-carboxylate
  参考文献：
  名称：

  Condensation reactions of guanidines with bis-electrophiles: formation of highly nitrogenous heterocycles

  摘要：

  2-Amino-1,4-dihydropyrimidines were reacted with bis-electrophiles to produce novel fused bipyrimidine, pyrimidoaminotriazine, and pyrimidosulfonamide scaffolds. In addition, a quinazoline library was constructed using a guanidine Atwal-Biginelli reaction with 1-(quinazolin-2-yl)guanidines. The product heterocycles have novel constitutions with high nitrogen atom counts and represent valuable additions to screening libraries for the discovery of new modulators of biological targets. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.04.127
• 作为产物：
  描述：

  4-氟苯胺 在 盐酸 、 碘 作用下， 以 乙醚 、 乙腈 为溶剂， 反应 0.17h， 生成 N-(6-Fluoro-4-methyl-quinazolin-2-yl)-guanidine
  参考文献：
  名称：

  Discovery of Novel Potent Reversible and Irreversible Myeloperoxidase Inhibitors Using Virtual Screening Procedure

  摘要：

  The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants. However, evidence has emerged that MPO-derived oxidants contribute to propagation of inflammatory diseases. Because of the deleterious effects of circulating MPO, there is a great interest in the development of new efficient and specific inhibitors. Here, we have performed a novel virtual screening procedure, depending on ligand-based pharmacophore modeling followed by structure-based virtual screening. Starting from a set of 727842 compounds, 28 molecules were selected by this virtual method and tested on MPO in vitro. Twelve out of 28 compounds were found to have an IC50 less than 5 mu M. The best inhibitors were 2-(7-methoxy-4-methylquinazolin-2-yl)guanidine (28) and (R)-2-(14(2,3-dihydro-1H-imidazol-2-yl-methyl)pyrrolidin-3-yl)-5-fluoro-1H-benzo[d]imidazole (42) with IC50 values of 44 and 50 nM, respectively. Studies on the mechanism of inhibition suggest that 28 is the first potent mechanism-based inhibitor and inhibits irreversibly MPO at nanomolar concentration.

  DOI：

  10.1021/acs.jmedchem.7b00285

文献信息

• [EN] COMPOUNDS TARGETING DUAL G-QUADRUPLEX DNA AND STAT3<br/>[FR] COMPOSÉS CIBLANT L'ADN DOUBLE G-QUADRUPLEXE ET LE STAT3
  申请人：SABOURI NASIM

  公开号：WO2020263164A1

  公开（公告）日：2020-12-30

  The present invention relates to novel quinazoline compounds having the formula (I) or (II): (I) (II). The compounds are active both as stabilizers of G-quadruplex DNA structures and as inhibitors of STAT3 phosphorylation. The disclosed compounds are useful in medical treatment, such as the treatment of cancer.

  本发明涉及具有化学式(I)或(II)的新型喹唑啉化合物：(I) (II)。这些化合物既可作为G-四链体DNA结构的稳定剂，又可作为STAT3磷酸化的抑制剂。所述化合物在医疗治疗方面具有用途，例如用于癌症治疗。
• Discovery of Novel Potent Reversible and Irreversible Myeloperoxidase Inhibitors Using Virtual Screening Procedure
  作者：Jalal Soubhye、Ibaa Chikh Alard、Iyas Aldib、Martine Prévost、Michel Gelbcke、Annelise De Carvalho、Paul G. Furtmüller、Christian Obinger、Jörg Flemmig、Sara Tadrent、Franck Meyer、Alexandre Rousseau、Jean Nève、Véronique Mathieu、Karim Zouaoui Boudjeltia、François Dufrasne、Pierre Van Antwerpen

  DOI：10.1021/acs.jmedchem.7b00285

  日期：2017.8.10

  The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants. However, evidence has emerged that MPO-derived oxidants contribute to propagation of inflammatory diseases. Because of the deleterious effects of circulating MPO, there is a great interest in the development of new efficient and specific inhibitors. Here, we have performed a novel virtual screening procedure, depending on ligand-based pharmacophore modeling followed by structure-based virtual screening. Starting from a set of 727842 compounds, 28 molecules were selected by this virtual method and tested on MPO in vitro. Twelve out of 28 compounds were found to have an IC50 less than 5 mu M. The best inhibitors were 2-(7-methoxy-4-methylquinazolin-2-yl)guanidine (28) and (R)-2-(14(2,3-dihydro-1H-imidazol-2-yl-methyl)pyrrolidin-3-yl)-5-fluoro-1H-benzo[d]imidazole (42) with IC50 values of 44 and 50 nM, respectively. Studies on the mechanism of inhibition suggest that 28 is the first potent mechanism-based inhibitor and inhibits irreversibly MPO at nanomolar concentration.
• Condensation reactions of guanidines with bis-electrophiles: formation of highly nitrogenous heterocycles
  作者：David M. Arnold、Matthew G. LaPorte、Shelby M. Anderson、Peter Wipf

  DOI：10.1016/j.tet.2013.04.127

  日期：2013.9

  2-Amino-1,4-dihydropyrimidines were reacted with bis-electrophiles to produce novel fused bipyrimidine, pyrimidoaminotriazine, and pyrimidosulfonamide scaffolds. In addition, a quinazoline library was constructed using a guanidine Atwal-Biginelli reaction with 1-(quinazolin-2-yl)guanidines. The product heterocycles have novel constitutions with high nitrogen atom counts and represent valuable additions to screening libraries for the discovery of new modulators of biological targets. (C) 2013 Elsevier Ltd. All rights reserved.