Functionalized N,N-Diphenylamines as Potent and Selective EPAC2 Inhibitors

Christopher T. Wild; Yingmin Zhu; Ye Na; Fang Mei; Marcus A. Ynalvez; Haiying Chen; Xiaodong Cheng; Jia Zhou

doi:10.1021/acsmedchemlett.5b00477

Functionalized N,N-Diphenylamines as Potent and Selective EPAC2 Inhibitors

Christopher T. Wild, Yingmin Zhu, Ye Na, Fang Mei, Marcus A. Ynalvez, Haiying Chen, Xiaodong Cheng, Jia Zhou

Pharmacology & Toxicology

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

15 Scopus citations

Abstract

N,N-Diphenylamines were discovered as potent and selective EPAC2 inhibitors. A study was conducted to determine the structure-activity relationships in a series of inhibitors of which several compounds displayed submicromolar potencies. Selectivity over the related EPAC1 protein was also demonstrated. Computational modeling reveals an allosteric site that is distinct from the cAMP binding domain shared by both EPAC isoforms, providing a theory with regards to subtype selectivity.

Original language	English (US)
Pages (from-to)	460-464
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	7
Issue number	5
DOIs	https://doi.org/10.1021/acsmedchemlett.5b00477
State	Published - May 12 2016

Keywords

Buchwald-Hartwig amination
Exchange proteins directly activated by cAMP (EPAC) inhibitors
diphenylamines
structure-activity relationship

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/acsmedchemlett.5b00477

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abstract = "N,N-Diphenylamines were discovered as potent and selective EPAC2 inhibitors. A study was conducted to determine the structure-activity relationships in a series of inhibitors of which several compounds displayed submicromolar potencies. Selectivity over the related EPAC1 protein was also demonstrated. Computational modeling reveals an allosteric site that is distinct from the cAMP binding domain shared by both EPAC isoforms, providing a theory with regards to subtype selectivity.",

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AU - Zhu, Yingmin

AU - Na, Ye

AU - Mei, Fang

AU - Ynalvez, Marcus A.

AU - Chen, Haiying

AU - Cheng, Xiaodong

AU - Zhou, Jia

PY - 2016/5/12

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AB - N,N-Diphenylamines were discovered as potent and selective EPAC2 inhibitors. A study was conducted to determine the structure-activity relationships in a series of inhibitors of which several compounds displayed submicromolar potencies. Selectivity over the related EPAC1 protein was also demonstrated. Computational modeling reveals an allosteric site that is distinct from the cAMP binding domain shared by both EPAC isoforms, providing a theory with regards to subtype selectivity.

KW - Buchwald-Hartwig amination

KW - Exchange proteins directly activated by cAMP (EPAC) inhibitors

KW - diphenylamines

KW - structure-activity relationship

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Functionalized N,N-Diphenylamines as Potent and Selective EPAC2 Inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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