5-fluoro-2-(2-methoxybenzyloxy)pyrimidin-4-amine | 1174379-10-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-fluoro-2-(2-methoxybenzyloxy)pyrimidin-4-amine
• 英文别名: 5-fluoro-2-[(2-methoxyphenyl)methoxy]pyrimidin-4-amine
• CAS: 1174379-10-2
• 化学式: C₁₂H₁₂FN₃O₂
• 分子量: 249.245
• InChiKey: RPMHURLSFCZETM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-fluoro-2-(2-methoxybenzyloxy)pyrimidin-4-amine 、 2-溴苯磺酰氯 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Development, Optimization, and Validation of a High Throughput Screening Assay for Identification of Tat and Type II Secretion Inhibitors of Pseudomonas aeruginosa

  摘要：

  Antibiotics are becoming less effective in treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa. Antimicrobial therapies based on the inhibition of specific virulence-related traits, as opposed to growth inhibitors, constitute an innovative and appealing approach to tackle the threat of P. aeruginosa infections. The twin-arginine translocation (Tat) pathway plays an important role in the pathogenesis of P. aeruginosa, and constitutes a promising target for the development of anti-pseudomonal drugs. In this study we developed and optimized a whole-cell, one-well assay, based on native phospholipase C activity, to identify compounds active against the Tat system. Statistical robustness, sensitivity and consequently suitability for high-throughput screening (HTS) were confirmed by a dry run/pre-screening test scoring a Z' of 0.82 and a signal-to-noise ratio of 49. Using this assay, we evaluated ca. 40,000 molecules and identified 59 initial hits as possible Tat inhibitors. Since phospholipase C is exported into the periplasm by Tat, and subsequently translocated across the outer membrane by the type II secretion system (T2SS), our assay could also identify T2SS inhibitors. To validate our hits and discriminate between compounds that inhibited either Tat or T2SS, two separate counter assays were developed and optimized. Finally, three Tat inhibitors and one T2SS inhibitor were confirmed by means of dose-response analysis and additional counter and confirming assays. Although none of the identified inhibitors was suitable as a lead compound for drug development, this study validates our assay as a simple, efficient, and HTS compatible method for the identification of Tat and T2SS inhibitors.

  DOI：

  10.3389/fcimb.2019.00250
• 作为产物：
  描述：

  2-甲氧基苯甲醇 、 4-氨基-2-氯-5-氟嘧啶 在 sodium hydride 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 以73%的产率得到5-fluoro-2-(2-methoxybenzyloxy)pyrimidin-4-amine
  参考文献：
  名称：

  Development, Optimization, and Validation of a High Throughput Screening Assay for Identification of Tat and Type II Secretion Inhibitors of Pseudomonas aeruginosa

  摘要：

  Antibiotics are becoming less effective in treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa. Antimicrobial therapies based on the inhibition of specific virulence-related traits, as opposed to growth inhibitors, constitute an innovative and appealing approach to tackle the threat of P. aeruginosa infections. The twin-arginine translocation (Tat) pathway plays an important role in the pathogenesis of P. aeruginosa, and constitutes a promising target for the development of anti-pseudomonal drugs. In this study we developed and optimized a whole-cell, one-well assay, based on native phospholipase C activity, to identify compounds active against the Tat system. Statistical robustness, sensitivity and consequently suitability for high-throughput screening (HTS) were confirmed by a dry run/pre-screening test scoring a Z' of 0.82 and a signal-to-noise ratio of 49. Using this assay, we evaluated ca. 40,000 molecules and identified 59 initial hits as possible Tat inhibitors. Since phospholipase C is exported into the periplasm by Tat, and subsequently translocated across the outer membrane by the type II secretion system (T2SS), our assay could also identify T2SS inhibitors. To validate our hits and discriminate between compounds that inhibited either Tat or T2SS, two separate counter assays were developed and optimized. Finally, three Tat inhibitors and one T2SS inhibitor were confirmed by means of dose-response analysis and additional counter and confirming assays. Although none of the identified inhibitors was suitable as a lead compound for drug development, this study validates our assay as a simple, efficient, and HTS compatible method for the identification of Tat and T2SS inhibitors.

  DOI：

  10.3389/fcimb.2019.00250

文献信息

• 5-FLUORO PYRIMIDINE DERIVATIVES
  申请人：Benko Zoltan L.

  公开号：US20090203647A1

  公开（公告）日：2009-08-13

  This present disclosure is related to the field of 5-fluoro pyrimidines and their derivatives and to the use of these compounds as fungicides.

  本公开涉及5-氟嘧啶及其衍生物领域，以及将这些化合物用作杀真菌剂的用途。
• 5-fluoro pyrimidine derivatives
  申请人：DOW AGROSCIENCES LLC

  公开号：US09204653B2

  公开（公告）日：2015-12-08

  This present disclosure is related to the field of 5-fluoro pyrimidines and their derivatives and to the use of these compounds as fungicides.

  本公开涉及5-氟嘧啶及其衍生物领域，以及将这些化合物用作杀真菌剂的用途。
• 5-FLUORO PYRIMIDINE DERIVATIVES AS FUNGICIDES
  申请人：Dow AgroSciences, LLC

  公开号：EP2562165A1

  公开（公告）日：2013-02-27

  This present disclosure is related to the field of 5-fluoro pyrmidines and their derivatives and to the use of these compounds as fungicides.

  本公开涉及 5-氟吡啶及其衍生物领域，以及这些化合物作为杀菌剂的用途。
• 4-AMINO-5-FLUORO-PYRIMIDINE DERIVATIVES AS FUNGICIDES
  申请人：Dow AgroSciences LLC

  公开号：EP2252594B1

  公开（公告）日：2015-08-19
• N-CYANO-4-AMINO-5-FLUORO-PYRIMIDINE DERIVATIVES AS FUNGICIDES
  申请人：Dow AgroSciences, LLC

  公开号：EP2562162B1

  公开（公告）日：2015-08-19