title: High-throughput prediction of blood-brain partitioning: a thermodynamic approach.
abstract: A high-throughput in silico screening tool for potentially CNS active compounds was developed on the basis of the correlation of solvation free energies and blood-brain partitioning (log(cbrain/cblood) = log BB) data available from experimental sources. Utilizing a thermodynamic approach, solvation free energies were calculated by the fast and efficient generalized Born/surface area continuum solvation model, which enabled us to evaluate more than 10 compounds/min. Our training set involved a structurally diverse set of 55 compounds and yielded a function of log BB = 0.035Gsolv + 0.2592 (r = 0.85, standard error 0.37). Calculation of solvation free energies for 8700 CNS active compounds (CIPSLINE database) revealed that Gsolv is higher than -50 kJ/mol for the 96% of these compounds which can be used as suitable criteria for the identification of compounds preferable for CNS penetration.
authors.affiliation: Computer Assisted Drug Discovery, Gedeon Richter Ltd, Budapest, Hungary. gy.keseru@richter.hu
authors.forename: G M
authors.initials: GM
authors.lastname: Keserü
authors.forename: L
authors.initials: L
authors.lastname: Molnár
mesh_terms: D001812:Blood-Brain Barrier; D002491:Central Nervous System Agents / Q000737:chemistry / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D008954:Models, Biological; D013816:Thermodynamics
chemical_list: D002491:Central Nervous System Agents