2. Academic Validation
  3. Structure-Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors

Structure-Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors

  • ACS Med Chem Lett. 2017 Oct 2;8(11):1183-1187. doi: 10.1021/acsmedchemlett.7b00358.
Yogesh A Sonawane 1,  Yingmin Zhu 2,  Jered C Garrison 1,  Edward L Ezell 1,  Muhammad Zahid 1,  Xiaodong Cheng 2,  Amarnath Natarajan 1 1 1 1
Affiliations

Affiliations

  • 1 Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, Departments of Pharmaceutical Sciences, Environmental, Agricultural and Occupational Health, and Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68022, United States.
  • 2 Department of Integrative Biology and Pharmacology and Texas Therapeutics Institute, University of Texas Health Science Center, Houston, Texas 77030, United States.
PMID: 29375750 DOI: 10.1021/acsmedchemlett.7b00358
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.

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