2-(2,5-dimethylbenzylsulfanyl)-6-oxo-4-piperidin-4-yl-1,6-dihydro-pyrimidine-5-carbonitrile | 1383539-75-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(2,5-dimethylbenzylsulfanyl)-6-oxo-4-piperidin-4-yl-1,6-dihydro-pyrimidine-5-carbonitrile
• 英文别名: 2-(2,5-Dimethylbenzylsulfanyl)-6-Oxo-4-Piperidin-4-Yl-1,6-Dihydro-Pyrimidine-5-Carbonitrile；2-[(2,5-dimethylphenyl)methylsulfanyl]-6-oxo-4-piperidin-4-yl-1H-pyrimidine-5-carbonitrile
• CAS: 1383539-75-0
• 化学式: C₁₉H₂₂N₄OS
• 分子量: 354.476
• InChiKey: UURFXOBWODKYTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(5-cyano-2-mercapto-6-oxo-1,6-dihydro-pyrimidin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 20.0h， 生成 2-(2,5-dimethylbenzylsulfanyl)-6-oxo-4-piperidin-4-yl-1,6-dihydro-pyrimidine-5-carbonitrile
  参考文献：
  名称：

  [EN] MODULATORS OF EXCHANGE PROTEINS DIRECTLY ACTIVATED BY CAMP (EPACS)
  [FR] MODULATEURS DE PROTÉINES D'ÉCHANGE DIRECTEMENT ACTIVÉES PAR L'AMPC (EPAC)

  摘要：

  该发明的实施例涉及抑制EPAC蛋白活性的化合物以及使用这些化合物的方法。发明人已经开发了一种敏感且稳健的高通量筛选（HTS）测定方法，用于识别EPAC特异性抑制剂（Tsalkova等人（2012年）PLOS ONE 7(1)：e30441）。

  公开号：

  WO2013119931A1

文献信息

• MODULATORS OF EXCHANGE PROTEINS DIRECTLY ACTIVATED BY CAMP (EPACS)
  申请人：The Board of Regents of the University of Texas System

  公开号：US20150110809A1

  公开（公告）日：2015-04-23

  Embodiments of the invention are directed to compounds that inhibit an activity of EP AC proteins and methods of using the same. The inventors have developed a sensitive and robust high throughput screening (HTS) assay for the purpose of identifying EPAC specific inhibitors (Tsalkova et al. (2012) PLOS ONE 7 (1):e30441).

  本发明的实施例涉及抑制EPAC蛋白活性的化合物及其使用方法。发明人开发了一种灵敏且强大的高通量筛选（HTS）检测方法，以识别EPAC特异性抑制剂（TSalkova等人（2012）PLOS ONE 7（1）：e30441）。
• 5-Cyano-6-oxo-1,6-dihydro-pyrimidines as potent antagonists targeting exchange proteins directly activated by cAMP
  作者：Haijun Chen、Tamara Tsalkova、Fang C. Mei、Yaohua Hu、Xiaodong Cheng、Jia Zhou

  DOI：10.1016/j.bmcl.2012.04.082

  日期：2012.6

  Exchange proteins directly activated by cAMP (Epac) are a family of guanine nucleotide exchange factors that regulate a wide variety of intracellular processes in response to second messenger cAMP. To explore the structural determinants for Epac antagonist properties of high throughput screening (HTS) hit ESI-08, pyrimidine 1, a series of 5-cyano-6-oxo-1,6-dihydro-pyrimidine analogues have been synthesized and evaluated for their activities for Epac inhibition. Structure-activity relationship (SAR) analysis led to the identification of three more potent Epac antagonists (6b, 6g, and 6h). These inhibitors may serve as valuable pharmacological probes for further elucidation of the physiological functions and mechanisms of Epac regulation. Our SAR results and molecular docking studies have also revealed that further optimization of the moieties at the C-6 position of pyrimidine scaffold may allow us to discover more potent Epac-specific antagonists. (C) 2012 Elsevier Ltd. All rights reserved.
• US9539256B2
  申请人：——

  公开号：US9539256B2

  公开（公告）日：2017-01-10