Structure-Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors

Yogesh A. Sonawane; Yingmin Zhu; Jered C. Garrison; Edward L. Ezell; Muhammad Zahid; Xiaodong Cheng; Amarnath Natarajan

doi:10.1021/acsmedchemlett.7b00358

Structure-Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors

Yogesh A. Sonawane, Yingmin Zhu, Jered C. Garrison, Edward L. Ezell, Muhammad Zahid, Xiaodong Cheng, Amarnath Natarajan

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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	https://doi.org/10.1021/acsmedchemlett.7b00358
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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10.1021/acsmedchemlett.7b00358

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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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AU - Sonawane, Yogesh A.

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AU - Zahid, Muhammad

AU - Cheng, Xiaodong

AU - Natarajan, Amarnath

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

Abstract

Keywords

ASJC Scopus subject areas

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