Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1183-1187 |
| Number of pages | 5 |
| Journal | ACS Medicinal Chemistry Letters |
| Volume | 8 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 9 2017 |
Keywords
- dynamic NMR
- exchange protein directly activated by cAMP
- rotamer
- tetrahydroquinoline
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry
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Sonawane, Y. A., Zhu, Y., Garrison, J. C., Ezell, E. L., Zahid, M., Cheng, X., & Natarajan, A. (2017). Structure-Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors. ACS Medicinal Chemistry Letters, 8(11), 1183-1187. https://doi.org/10.1021/acsmedchemlett.7b00358