Novel bivalent positive allosteric modulators of AMPA receptor.

A positive allosteric modulator of AMPA receptors has been designed using computer-aided molecular modeling techniques. It possessed a record high experimentally confirmed potency in the picomolar concentration range and belongs to a new type of bivalent AMPA receptor ligands containing bicyclo[3.3.

Calculation of aqueous solubility of crystalline un-ionized organic chemicals and drugs based on structural similarity and physicochemical descriptors.

Solubilities of crystalline organic compounds calculated according to AMP (arithmetic mean property) and LoReP (local one-parameter regression) models based on structural and physicochemical similarities are presented. We used data on water solubility of 2615 compounds in un-ionized form measured at 25±5 °C. The calculation results were compared with the equation based on the experimental data for lipophilicity and melting point.

[Acute intravenous toxicity to mice calculations on the basis local regression models in superoverlapping clusters (LRMSC)].

Modeling of quantitative structure--activity relationships between physicochemical descriptors of organic chemicals and their acute intravenous toxicity in mice have been presented. This approach includes three steps: structure-similarity chemicals selection for every chemical-of-interest (clusterization); construction of quantitative structure--toxicity models for every cluster (without including of chemical-of-interest); application of obtained QSAR equations for chemical-of-interest toxicity estimation. This approach has been applied for acute intravenous toxicity calculations of 10241 organic chemicals.

[Study of the neuroprotective action of hybrid structures based on fullerene C60].

The neuroprotective action of hybrid structures based on fullerene C60 with attached proline amino acid has been studied. Hybrid structures contained natural antioxidant carnosine or addends with one or two nitrate groups. It has been shown that all studied compounds had antioxidant activity and decreased the concentration of malondialdehyde in homogenates of the rat brain.

Prediction of Acute Rodent Toxicity on the Basis of Chemical Structure and Physicochemical Similarity.

A development of the Arithmetic Mean Toxicity (AMT) approach is presented in this article. Twenty six physicochemical descriptors, calculated by using the HYBOT program, along with molecular weight and lipophilicity were included in the selection of structural and physicochemical neighbours (analogues). Toxicity predictions of 906 chemicals from the REACH Pre-Registration Substance (PRS) list were carried out with the application of six nearest structural neighbours and three pairs of structural/physicochemical neighbours on the basis of molecular polarizability, the sum of negative atomic charges in a molecule, the sum of H-bond acceptor and donor factors and the octanol-water partition coefficient.