(5-cyano-4-cyclohexyl-6-oxo-1,6-dihydro-pyrimidln-2-ylsulfanyl)-acetic acid

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (5-cyano-4-cyclohexyl-6-oxo-1,6-dihydro-pyrimidln-2-ylsulfanyl)-acetic acid
• 英文别名: (5-cyano-4-cyclohexyl-6-oxo-1,6-dihydropyrimidin-2-ylsulfanyl)acetic acid；2-[(5-cyano-4-cyclohexyl-6-oxo-1H-pyrimidin-2-yl)sulfanyl]acetic acid
• 化学式: C₁₃H₁₅N₃O₃S
• 分子量: 293.346
• InChiKey: SMSRANLRYFGDLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (5-cyano-4-cyclohexyl-6-oxo-1,6-dihydro-pyrimidln-2-ylsulfanyl)-acetic acid 、 2,4,6-三甲基苯胺 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以80%的产率得到2-(5-cyano-4-cyclohexyl-6-oxo-1,6-dihydro-pyrimidin-2-ylsulfanyl)-N-(2,4,6-trimethyl-phenyl)-acetamide
  参考文献：
  名称：

  5-Cyano-6-oxo-1,6-dihydro-pyrimidines as potent antagonists targeting exchange proteins directly activated by cAMP

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2012.04.082
• 作为产物：
  描述：

  环己烷基甲醛 在 哌啶 、 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 9.0h， 生成 (5-cyano-4-cyclohexyl-6-oxo-1,6-dihydro-pyrimidln-2-ylsulfanyl)-acetic acid
  参考文献：
  名称：

  用于葡萄糖神经酰胺水解的 ß-葡萄糖脑苷脂酶激活剂的鉴定

  摘要：

  我们首次报道了激活天然葡萄糖脑苷脂酶（GCase）底物葡萄糖神经酰胺水解成神经酰胺和葡萄糖的新型化合物。来自两种不同化学型的化合物结合到 GCase 上的两个不同位点：一个 ( 32 ) 靠近底物结合位点，而另一个 ( 31 ) 距离催化袋更远。 GlcCer：葡萄糖神经酰胺

  DOI：

  10.1002/cmdc.202300548

文献信息

• [EN] MODULATORS OF EXCHANGE PROTEINS DIRECTLY ACTIVATED BY CAMP (EPACS)<br/>[FR] MODULATEURS DE PROTÉINES D'ÉCHANGE DIRECTEMENT ACTIVÉES PAR L'AMPC (EPAC)
  申请人：UNIV TEXAS

  公开号：WO2013119931A1

  公开（公告）日：2013-08-15

  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).

  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）。
• 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）。
• METHODS OF TREATING RICKETTSIA USING EXCHANGE PROTEINS DIRECTLY ACTIVATED BY CAMP (EPACS) INHIBITORS
  申请人：Gong Bin

  公开号：US20140348853A1

  公开（公告）日：2014-11-27

  Embodiments of the invention are directed to compounds that inhibit an activity of EPAC proteins and methods of using the same.
• US9539256B2
  申请人：——

  公开号：US9539256B2

  公开（公告）日：2017-01-10
• [EN] ANTIMICROBIAL METHODS USING INHIBITORS OF EXCHANGE PROTEINS DIRECTLY ACTIVATED BY CAMP (EPAC)<br/>[FR] PROCÉDÉS ANTIMICROBIENS UTILISANT DES INHIBITEURS DE PROTÉINES D'ÉCHANGE DIRECTEMENT ACTIVÉES PAR L'AMPC (EPAC)
  申请人：UNIV TEXAS

  公开号：WO2014123680A1

  公开（公告）日：2014-08-14

  Embodiments of the invention are directed to compositions and method for treating a viral infection. Embodiments of the invention are directed to medicine and health care. Certain embodiments are directed to methods of treating infectious disease. Additional embodiments are directed to the use of inhibitors of exchange proteins directly activated by cAMP (Epac) to treat viral infections.