1423915-05-2Relevant academic research and scientific papers
Structure-Activity Relationship Studies of Substituted 2-(Isoxazol-3-yl)-2-oxo-N′-phenyl-acetohydrazonoyl Cyanide Analogues: Identification of Potent Exchange Proteins Directly Activated by cAMP (EPAC) Antagonists
Ye, Na,Zhu, Yingmin,Chen, Haijun,Liu, Zhiqing,Mei, Fang C.,Wild, Christopher,Chen, Haiying,Cheng, Xiaodong,Zhou, Jia
, p. 6033 - 6047 (2015/08/24)
Exchange proteins directly activated by cAMP (EPAC) as guanine nucleotide exchange factors mediate the effects of the pivotal second messenger cAMP, thereby regulating a wide variety of intracellular physiological and pathophysiological processes. A series of novel 2-(isoxazol-3-yl)-2-oxo-N′-phenyl-acetohydrazonoyl cyanide EPAC antagonists was synthesized and evaluated in an effort to optimize properties of the previously identified high-throughput (HTS) hit 1 (ESI-09). Structure-activity relationship (SAR) analysis led to the discovery of several more active EPAC antagonists (e.g., 22 (HJC0726), 35 (NY0123), and 47 (NY0173)) with low micromolar inhibitory activity. These inhibitors may serve as valuable pharmacological probes to facilitate our efforts in elucidating the biological functions of EPAC and developing potential novel therapeutics against human diseases. Our SAR results have also revealed that further modification at the 3-, 4-, and 5-positions of the phenyl ring as well as the 5-position of the isoxazole moiety may allow for the development of more potent EPAC antagonists.
MODULATORS OF EXCHANGE PROTEINS DIRECTLY ACTIVATED BY CAMP (EPACS)
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Paragraph 0214; 0215, (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).
Efficient synthesis of ESI-09, a novel non-cyclic nucleotide EPAC antagonist
Chen, Haijun,Ding, Chunyong,Wild, Christopher,Liu, Huiling,Wang, Tianzhi,White, Mark A.,Cheng, Xiaodong,Zhou, Jia
, p. 1546 - 1549 (2013/03/14)
A concise and efficient synthetic approach to producing a novel non-cyclic nucleotide EPAC antagonist ESI-09 and its new analogs is reported. Key features of the synthesis include a mild and reliable one-pot procedure for an isoxazole synthon, as well as a modified one-pot protocol for the cyanomethyl ketone key intermediate. The synthesis requires inexpensive starting materials and only three linear steps for the completion in a total yield of 53%.
