[QSAR investigation of acute toxicity of organic compounds during oral administration to mice].

The effect of the structure of organic compounds on the acute toxicity upon oral injection in mice was studied using 2D simplex representation of the molecular structure and Random forest (RF) methods. Satisfactory quantitative structure-activity relationship (QSAR) models were constructed (R2 test = 0,61-0,62). The interpretation of the obtained QSAR models was carried out.

Contribution assessment of multiparameter optimization descriptors in CNS penetration.

Assessment of the influence of six physicochemical properties used in the multiparameter optimization (MPO) approach for chemical penetration of the blood-brain barrier was carried out by means of application of logistic regression and multiple linear regression, using a data set of 578 diverse chemicals. It was found that use of an aggregation MPO-score descriptor did not give satisfactory results with central nervous system (CNS)/non-CNS classification. Thus an application of the MPO approach for CNS penetration is ambiguous.

Classification (Agonist/Antagonist) and Regression "Structure-Activity" Models of Drug Interaction with 5-HT6.

Introduction: One promising target for novel psychotropic drugs is the 5-HT6 receptor, GProtein- Coupled Receptor (GPCR) family, displaying seven transmembrane domains. There is considerable interest in how both 5-HT6 receptor agonist and antagonist compounds can have marked procognitive effects.

Methods: An exact structure of the 5-HT6 receptor is not available, so application of powerful methods of (Q)SAR and molecular modelling, which play an essential role in modern drug design, are currently limited to structure-based homology models.

Aqueous Drug Solubility: What Do We Measure, Calculate and QSPR Predict?

Detailed critical analysis of publications devoted to QSPR of aqueous solubility is presented in the review with discussion of four types of aqueous solubility (three different thermodynamic solubilities with unknown solute structure, intrinsic solubility, solubility in physiological media at pH=7.4 and kinetic solubility), variety of molecular descriptors (from topological to quantum chemical), traditional statistical and machine learning methods as well as original QSPR models.

Applications of Multi-Target Computer-Aided Methodologies in Molecular Design of CNS Drugs.

The discovery of drugs for diseases of the central nervous system (CNS) faces high attrition rates in clinical trials. Neural diseases are extremely complex in nature and typically associated with multiple drug targets. A conception of multi-target directed ligands (MTDL), widely applied to the discovery of cancer pharmaceuticals, may be a perspective solution for CNS diseases.