cGMP has a short-term effect on smooth muscle tone and a longer-term effect on responses to chronic drug treatment or proliferative signals. cGMP-Phosphodiesterase type 5 (PDE5) hydrolizes cGMP, and the result is smooth muscle contraction. PDE5 is a relatively novel therapeutic target
of various diseases, such as erectile dysfunction and pulmonary hypertension. The most intensively examined and marketed PDE5 inhibitor was sildenafil (Viagra) but recently vardenafil (Levitra) and tadalafil (Cialis) were launched with beneficial ADME parameters and PDE5 selectivity. The increasing
interest in PDE5 inhibition made it reasonable to collect the available inhibitory data from the scientific literature and set up a structure-activity relationship study. Chemical structures of 438 compounds and their cGMP-PDE5 inhibitory data (IC50) were collected from recently published
articles. In this paper physiology, regulation and inhibition of PDE5 (and briefly other PDE-s) are discussed and inhibitors are tabulated by the core structures. Finally, a general QSAR model built from these data is presented. All data used in the QSAR study were summarized in a Supplement
(for description please see the online version of the article).
Semmelweis University, Department of Pharmaceutical Chemistry, Hogyes E. u. 9., Budapest, 1092, Hungary.
Publication date: July 1, 2008
More about this publication?
Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.