Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors

EPAC proteins are therapeutic targets for the potential treatment of cardiac hypertrophy and cancer metastasis. Several laboratories use a tetrahydroquinoline analog, CE3F4, to dissect the role of EPAC1 in various disease states. Here, we report SAR studies with tetrahydroquinoline analogs that expl...

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Published in:ACS medicinal chemistry letters 2017-11, Vol.8 (11), p.1183-1187
Main Authors: Sonawane, Yogesh A, Zhu, Yingmin, Garrison, Jered C, Ezell, Edward L, Zahid, Muhammad, Cheng, Xiaodong, Natarajan, Amarnath
Format: Article
Language:English
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Letter
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Summary:EPAC proteins are therapeutic targets for the potential treatment of cardiac hypertrophy and cancer metastasis. Several laboratories use a tetrahydroquinoline analog, CE3F4, to dissect the role of EPAC1 in various disease states. Here, we report SAR studies with tetrahydroquinoline analogs that explore various functional groups. The most potent EPAC inhibitor 12a exists as a mixture of inseparable E (major) and Z (minor) rotamers. The rotation about the N-formyl group indeed impacts the activity against EPAC.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.7b00358