title: Functionalized N,N-Diphenylamines as Potent and Selective EPAC2 Inhibitors.
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.
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Wild
authors.affiliation: Department of Integrative Biology and Pharmacology and Texas Therapeutics Institute, University of Texas Health Science Center , Houston, Texas 77030, United States.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Ye
authors.initials: Y
authors.lastname: Na
authors.affiliation: Department of Integrative Biology and Pharmacology and Texas Therapeutics Institute, University of Texas Health Science Center , Houston, Texas 77030, United States.
authors.forename: Fang
authors.initials: F
authors.lastname: Mei
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Ynalvez
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Integrative Biology and Pharmacology and Texas Therapeutics Institute, University of Texas Health Science Center , Houston, Texas 77030, United States.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
keywords: Buchwald−Hartwig amination; Exchange proteins directly activated by cAMP (EPAC) inhibitors; diphenylamines; structure−activity relationship