title: 3D-QSAR studies on sildenafil analogues, selective phosphodiesterase 5 inhibitors.
abstract: Sildenafil, one of selective phosphodiesterase 5 (PDE5) inhibitors, is a widely used oral agent for the treatment of erectile dysfunction. To develop new PDE5 inhibitors with improved therapeutic efficacy, a series of sildenafil analogues have been prepared and their in vitro PDE5 inhibitory activities were evaluated. Their IC(50) values ranged from 423 to 0.05 nM. Herein, the results of 3D-QSAR (CoMFA and CoMSIA) analyses on these inhibitors are reported. Both CoMFA and CoMSIA gave reliable models with q(2) values >0.75 and r(2) values >0.99. The resulting CoMFA and CoMSIA models reveal a good correlation between the contour maps and the active site residues critical for the interaction with inhibitor, and nicely predict the key structural features of new analogues with improved activity and selectivity.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors.forename: Jakyung
authors.initials: J
authors.lastname: Yoo
authors.forename: Khac-Minh
authors.initials: KM
authors.lastname: Thai
authors.forename: Dae-Kee
authors.initials: DK
authors.lastname: Kim
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Park
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D008958:Models, Molecular; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology; D011687:Purines / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5