Formation of 2‑Imino Benzo[<i>e</i>]‑1,3-oxazin-4-ones from Reactions of Salicylic Acids and Anilines with HATU: Mechanistic and Synthetic Studies

We describe a new 1-[Bis­(dimethylamino)­methylene]-1<i>H</i>-1,2,3-triazolo­[4,5-<i>b</i>]­pyridinium 3-oxide hexafluorophosphate (HATU)-mediated coupling reaction to produce 2-imino benzo­[<i>e</i>]-1,3-oxazin-4-ones from salicylic acids and anilines. Mechanistic studies support a reaction pathway in which HATU mediates carbon transfer to the initially formed salicylanilides to form in succession reactive tetramethylisouronium and <i>N</i>-acyl­(dimethyl)­isouronium intermediates, which then undergo imine–iminium exchange to generate the desired oxazinones

Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors

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 <b>12a</b> exists as a mixture of inseparable <i>E</i> (major) and <i>Z</i> (minor) rotamers. The rotation about the <i>N</i>-formyl group indeed impacts the activity against EPAC

Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors

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 <b>12a</b> exists as a mixture of inseparable <i>E</i> (major) and <i>Z</i> (minor) rotamers. The rotation about the <i>N</i>-formyl group indeed impacts the activity against EPAC