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The key importance of lipophilicity in bio-studies is discussed for beta-blockers. Examples of their lipophilicity-dependent pharmacological properties including pharmacokinetic, pharmacodynamic and clinical aspects are reviewed. Comprehensive lipophilicity compilations of beta-blockers are lacking so far. LogP calculations with 10 programs for 30(More)
ATP-sensitive potassium channels (K(ATP) channels) are heteromeric complexes of pore-forming inwardly rectifying potassium channel subunits and regulatory sulfonylurea receptor subunits. K(ATP) channels were identified in a variety of tissues including muscle cells, pancreatic beta-cells, and various neurons. They are regulated by the intracellular ATP/ADP(More)
About 20 non-peptide angiotensin II receptor antagonists are in various stages of clinical development. Different modeling approaches were used to predict the pharmacophoric requirements for AT(1) (angiotensin II receptor subtype 1) affinity. However, to our knowledge, none was used to predict both the selectivity toward AT(1) and AT(2) (angiotensin II(More)
The predictive power of four calculation procedures for molecular lipophilicity is checked by comparing with experimental data (log P and chromatographical RMw) taken from the literature. Two sets of test compounds are used: the first comprises simple organic molecules and the second consists of more complicated drug molecules. Our comparative evaluation(More)
An investigation was carried out towards a qualitative and quantitative structure-activity relationship of verapamil based on an analysis of the frequency-dependent negative inotropic action exerted in cat papillary muscles by various groups of verapamil derivatives. (1) Substituents of the benzene ring near the asymmetric carbon atom and the isopropyl(More)
Binding of antiarrhythmics to phospholipids has been quantified by measuring the drug-induced fluorescence increase in 8-anilino-1-napthalenesulfonate (ANS)-treated phosphatidylcholine membranes. The ability of test compounds to increase fluorescence intensity to 50% varies between 1.3 and 88 X 10(-6) M, exhibiting a potency ratio of 1.8 log units. The(More)
We first review the state-of-the-art in development of log P prediction approaches falling in two major categories: substructure-based and property-based methods. Then, we compare the predictive power of representative methods for one public (N = 266) and two in house datasets from Nycomed (N = 882) and Pfizer (N = 95809). A total of 30 and 18 methods were(More)
All four currently FDA-approved drug-eluting stents (DESs) contain a durable polymeric coating which can negatively impact vascular healing processes and eventually lead to adverse cardiac events. Aim of this study was the pre-clinical assessment of two novel rapamycin-eluting stent (RES) coating technologies that abstain from use of a durable polymer. Two(More)
Ligand- (GRIND) and structure-based (GLUE/GRIND) 3D-QSAR approaches were compared for 55 (aryl-)bridged 2-aminobenzonitriles inhibiting HIV-1 reverse transcriptase (HIV-1 RT). The ligand-based model was built from conformers selected by in vacuo minimization. The available X-ray structure of 3v in complex with HIV-1 RT allowed comparative structure-based(More)
Virtual fragment screening (VFS) is a promising new method that uses computer models to identify small, fragment-like biologically active molecules as useful starting points for fragment-based drug discovery (FBDD). Training sets of true active and inactive fragment-like molecules to construct and validate target customized VFS methods are however lacking.(More)