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...

Descripción completa

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
_version_ 1783293734541066240
author Sonawane, Yogesh A.
Zhu, Yingmin
Garrison, Jered C.
Ezell, Edward L.
Zahid, Muhammad
Cheng, Xiaodong
Natarajan, Amarnath
author_facet Sonawane, Yogesh A.
Zhu, Yingmin
Garrison, Jered C.
Ezell, Edward L.
Zahid, Muhammad
Cheng, Xiaodong
Natarajan, Amarnath
author_sort Sonawane, Yogesh A.
collection PubMed
description [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.
format Online
Article
Text
id pubmed-5774307
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-57743072018-01-25 Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors Sonawane, Yogesh A. Zhu, Yingmin Garrison, Jered C. Ezell, Edward L. Zahid, Muhammad Cheng, Xiaodong Natarajan, Amarnath ACS Med Chem Lett [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. American Chemical Society 2017-10-02 /pmc/articles/PMC5774307/ /pubmed/29375750 http://dx.doi.org/10.1021/acsmedchemlett.7b00358 Text en Copyright © 2017 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Sonawane, Yogesh A.
Zhu, Yingmin
Garrison, Jered C.
Ezell, Edward L.
Zahid, Muhammad
Cheng, Xiaodong
Natarajan, Amarnath
Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors
title Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors
title_full Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors
title_fullStr Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors
title_full_unstemmed Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors
title_short Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors
title_sort structure–activity relationship studies with tetrahydroquinoline analogs as epac inhibitors
url 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
work_keys_str_mv AT sonawaneyogesha structureactivityrelationshipstudieswithtetrahydroquinolineanalogsasepacinhibitors
AT zhuyingmin structureactivityrelationshipstudieswithtetrahydroquinolineanalogsasepacinhibitors
AT garrisonjeredc structureactivityrelationshipstudieswithtetrahydroquinolineanalogsasepacinhibitors
AT ezelledwardl structureactivityrelationshipstudieswithtetrahydroquinolineanalogsasepacinhibitors
AT zahidmuhammad structureactivityrelationshipstudieswithtetrahydroquinolineanalogsasepacinhibitors
AT chengxiaodong structureactivityrelationshipstudieswithtetrahydroquinolineanalogsasepacinhibitors
AT natarajanamarnath structureactivityrelationshipstudieswithtetrahydroquinolineanalogsasepacinhibitors

Ejemplares similares