Identification of phosphodiesterase-1 and 5 dual inhibitors by a ligand-based virtual screening optimized for lead evolution.
We identified new lead candidates which showed potent dual inhibition against phosphodiesterase-1 and 5 by a ligand-based virtual screening optimized for lead evolution. This virtual screening method, consisting of classification and regression tree analysis using 168 2-center pharmacophore descriptors and 12 macroscopic descriptors, demonstrated a high predictive ability for bioactivity of new chemical compounds. The obtained lead candidates were structurally diverse, although only the structure-activity relationship data of hydroxamic acid derivatives were used to configure the prediction model for the virtual screening.
Yamazaki
Kazuto
K
Sumitomo Pharmaceuticals Co., Ltd, 1-98, Kasugade Naka 3-Chome, Konohana-ku, Osaka 554-0022, Japan. kazuto-yamazaki@ds-pharma.co.jp
Kusunose
Naoto
N
Fujita
Katsuya
K
Sato
Hideshi
H
Asano
Shigehiro
S
Dan
Akihito
A
Kanaoka
Masaharu
M
D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006877:Hydroxamic Acids; D008024:Ligands; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases