Abstract
Protein structures and inhibitors of cGMP-specific phosphodiesterase 5 (PDE 5) have been widely studied. A new drug takes a lot time and money from lab to market. With the methodology of computer-aided drug design, it is able to save and decrease time and money in R&D. Using the way of protein-based and ligand-based design to provide information of finding new possible PDE5 inhibitors of high selectivity. First part of the experiment is based on mechanism of inhibition of tadalafil, and 1500 compounds are found out with two different scoring functions (Goldscore and Chemscore) in GOLD software. Then we get 90 compounds through the filter of Pscore, Druglike and more precise parameter settings. Secondly, one hydrophobic, one ring aromatic, one hydrogen bond donor, and one hydrogen bond acceptor based pharmacophore models which are developed by a series of Tadalafil derivatives is able to estimate the inhibition activity of compounds, provide the clue of different inhibition mechanism between cis- form and trans-form derivatives, and virtually screen the chemical database.