E. J. Sybertz*, M. Czarniecki and H.-S. Ahn Pages 373 - 390 ( 18 )
The evolving biology of cGMP and understanding of its mechanisms of regulation are opening up new opportunities for discovery of drugs which can produce therapeutically desirable effects through alteration of cGMP levels. In particular the identification of potent and selective inhibitors of phosphodiesterases (PDE) which hydrolyze cGMP has been the objective of large drug discovery programs in recent years. This paper reviews the structure activity relationships of the recently discovered cGMP PDE inhibitors. Particular emphasis has been placed on the identification of novel structures and the structural elements which contribute to activity. The therapeutic potential of cGMP PDE inhibition is reviewed with an emphasis on cardiovascular diseases. Citing studies of Zaprinast, E4021, Win 58237 and SCH 51866 pharmacology the opportunities for the development of novel agents to treat angina pectoris, congestive heart failure, myocardial infarction, hypertension and atherosclerosisis are presented.