Discovery of hydroxamic acid analogs as dual inhibitors of phosphodiesterase-1 and -5

HTS and the following synthesis of a series of the compounds led us to the discovery of hydroxamic acid analogs as potent dual inhibitors of phosphodiesterase (PDE)-1 and 5. These compounds have highly related structure and deviation of the structure usually resulted in reduced potency. This result can be used to design other molecules that may be utilized for the therapy of cardiovascular symptoms that relates to cGMP level.

Graphical abstractHTS and the following synthesis of a series of compounds led us to the discovery of hydroxamic acid analogs as potent dual inhibitors of phosphodiesterase (PDE)-1 and -5. Some of them showed the expected potent vasodilatory effects with a rising level of cGMP.Figure optionsDownload full-size imageDownload as PowerPoint slide