1383539-69-2Relevant academic research and scientific papers
MODULATORS OF EXCHANGE PROTEINS DIRECTLY ACTIVATED BY CAMP (EPACS)
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Paragraph 0158, (2013/08/28)
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).
5-Cyano-6-oxo-1,6-dihydro-pyrimidines as potent antagonists targeting exchange proteins directly activated by cAMP
Chen, Haijun,Tsalkova, Tamara,Mei, Fang C.,Hu, Yaohua,Cheng, Xiaodong,Zhou, Jia
, p. 4038 - 4043 (2012/07/03)
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.
