Mstislav Igorevich Lavrov

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[3.3.1]nonane scaffold. The suggested structure could serve as a basis for further optimization and development of drugs for the treatment of neurodegenerative diseases, cognition enhancement, and improvement of memory.

Synthesis and AMPA-receptor modulating activity of benzodioxanecarboxylic and piperonylic acid derivatives

A series of amides of benzodioxane-6-carboxylic and piperonylic acids have been synthesized. Biological studies showed that some of the synthesized compounds influence the central nervous system (in particular, AMPA receptors).

The binding site for allosteric modulators of AMPA receptor

AMPA receptors, named after the selective agonist 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA), are classified in the group of glutamate ionotropic receptors and participate in many important neurophysiological processes involved in rapid synaptic stimulation transduction, memory formation, etc. [1]. The disturbance of activation of AMPA receptor causes certain pathologies including the most various neurodegenerative diseases (Parkinson’s disease, primary neuronal degeneration, etc.) and acute neurodegenerative disorders (hypoxia, ischemia, etc.) [1, 2]. For this reason, ligands of AMPA receptor were shown to be effective neuroprotective drugs, and the efforts of many researchers are aimed at searching for new effective ligands of this receptor.

Pharmacophore analysis of positive allosteric modulators of AMPA receptors

A 3D QSAR study of a set of positive allosteric modulators of AMPA receptors was performed using the CoMFA approach. It was shown that the van der Waals component introduces the major contribution to the predicted pEC50 values, while the contribution of the electrostatic component is minor. The pharmacophore hypothesis for positive allosteric modulators was generated and validated.

MM-GBSA and MM-PBSA performance in activity evaluation of AMPA receptor positive allosteric modulators

MM-GBSA and MM-PBSA performance in activity evaluation of AMPA receptor positive allosteric modulators Dmitry S. Karlov , Mstislav I. Lavrov, Vladimir A. Palyulin* and Nikolay S. Zefirov Department of Chemistry, Lomonosov Moscow State University, 1 Build. 3, Leninskie Gory, Moscow, 119991 Russian Federation; Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severny proezd, Chernogolovka, Moscow Region 142432, Russian Federation