The pharmacophore hypotheses of Ikr potassium channel blockers: novel class Ⅲ antiarrhythmic agents
Predictive pharmacophore models were developed for a large series of Ikr, potassium channel blockers as class Ⅲ antiarrhythmic agents using HypoGen in Catalyst software. The pharmacophore hypotheses were generated using a training set con sisting of 34 compounds carefully selected from documents. Their biological data, expressed as IC50, spanned from 1.5nM to 2.8 mM with 7 orders difference. The most predictive hypothesis (Hypol), consisting of four features (one positive ionizable feature, two aromatic rings and one hydrophobic group), had a best correlation coefficient of 0.825, a lowest rms deviation of 1.612, and a highest cost difference (null cost-total cost) of 77.552, which represents a true correlation and a good predictivity. The hypothesis Hypol was then validated by a test set consisting of 21 compounds and by a cross-validation of 95％ confidence level with randomizing the data using CatScramble program. Accordingly, our model has strong predictivity to identify structural diverse Ikr potassium channel blockers with desired biological activity by virtual screening.
Pharmacophore Hypothesis IKr potassium channel Blockers.
Lü-Pei Du Keng-Chang Tsai Min-Yong Li Qi-Dong You Lin Xia
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China Institute of Molecular Medicine and Department of Life Science, National Tsinghua Unviersity, Hsinch
国际会议
杭州
英文
1453-1459
2007-04-01（万方平台首次上网日期，不代表论文的发表时间）