Structure-Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors.

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.

• Authors: Yogesh A Sonawane, Yingmin Zhu, Jered C Garrison, Edward L Ezell, Muhammad Zahid, Xiaodong Cheng, Amarnath Natarajan
• Journal: ACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 8 Issue 11 Pg. 1183-1187 (Nov 09 2017) ISSN: 1948-5875 [Print] United States
• PMID: 29375750 (Publication Type: Journal Article)