Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors

[Image: see text] 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...

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Detalles Bibliográficos
Autores principales: Sonawane, Yogesh A., Zhu, Yingmin, Garrison, Jered C., Ezell, Edward L., Zahid, Muhammad, Cheng, Xiaodong, Natarajan, Amarnath
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774307/
https://www.ncbi.nlm.nih.gov/pubmed/29375750
http://dx.doi.org/10.1021/acsmedchemlett.7b00358
Descripción
Sumario:[Image: see text] 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.

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