Synthetic route optimization of Sumepirin antiepileptic drug candidate

In this work we describe the transformation of synthetic route of the antiepileptic drug candidate Sumepirin starting from discovery stage. Initial method included six step process requiring two steps of purification using colon chromatography and has poor overall yield of target compound. The process developed is convenient, scalable, technological and meet the most of conditions of green chemistry. The overall yield was increased up to 62.5% in four steps without colon chromatography purification which allows to obtain the target compound with purity of 99.5+% which is especially important for the active ingredient

Novel approach to 6-alkenyl-substituted pyridoxine derivatives based on the Heck reaction

© 2018 Elsevier Ltd A new synthetic approach to 6-alkenyl-substituted pyridoxine derivatives was developed based on the Heck reaction. The reaction, which was catalyzed using a mixture of Pd(OAc)2, (o-Tol)3P and Bu3N as a base, led to seven new 6-alkenyl pyridoxine derivatives. When acrylic acid was used the products of decarboxylation and dimerization were formed

Regioisomeric oximes and thiosemicarbazones derived from 6-substituted pyridoxines

The selective oxidation of 2- and 4-positioned hydroxymethyl groups of 6-methyl-2,3,4-tris(hydroxymethyl)pyridin-5-ol was developed and the thus obtained aldehydes were converted into their oximes and thiosemicarbazones. © 2012 Mendeleev Communications. All rights reserved

SYNTHETIC ROUTE OPTIMIZATION OF SUMEPIRIN ANTIEPILEPTIC DRUG CANDIDATE

Epilepsy is one of the most common chronic diseases of the nervous system in the world, which affects both children and adults. 30% of patients with epilepsy are pharmacoresistant. Sumepirin 1 is a novel antiepileptic drug candidate developed in the Scientific and Educational Center of Pharmaceutics of the Kazan Federal University and having pronounced antiseizure effect and improved safety profile. This compound is pyridoxine-based molecule with residue of methanesulfonic acid in the 6th position of pyridoxine ring.This work was supported by subsidy allocated to Kazan Federal University for the state assignment in the sphere of scientificactivities (project number 0671-2020-0053

The Study of the Conformation and Dynamics of the New Quaternary Phosphonium Salts by NMR Spectroscopy

A number of quaternary phosphonium salts on the basis of pyridoxine derivatives were investigated by nuclear magnetic resonance (NMR) spectroscopy methods. Conformational exchange processes for each compound in solution were studied using dynamic NMR experiments. Energy barriers of the conformational transitions were determined. © 2014 Springer-Verlag Wien

In-vitro antitumor activity of new quaternary phosphonium salts, derivatives of 3-hydroxypyridine

© 2018 Wolters Kluwer Health, Inc. All rights reserved. This work presents the results of in-vitro biological activity studies of three novel anticancer agents, phosphonium salts based on the 3-hydroxypyridine scaffold, including one derivative of 4-deoxypyridoxine. Proliferation and viability of cells treated with these compounds was assessed by the colony formation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Effects of the compounds on apoptosis and cell cycle were studied by flow cytometry using annexin V-FITC/propidium iodide and propidium iodide staining, respectively. The influence of the compounds on mitochondrial membrane potential and intracellular reactive oxygen species was evaluated using tetramethyl rhodamine ethyl and DCFHA staining. Western blot analysis was used to study the changes in the expression of Bcl-xL, Bax, and caspase-3 apoptotic proteins. The treatment of ovarian adenocarcinoma cells OVCAR-4 with the tested compounds inhibited the growth and induced cell cycle arrest in the G1 phase. 3-Hydroxypyridine derivatives induced apoptosis by hyperexpression of Bax and caspase-3, whereas 4-deoxypyridoxine derivative induced cell death partly by reactive oxygen species generation and caspase-3 hyperexpression. These results indicate that the quaternary phosphonium salts studied represent potential therapeutic agents for the treatment of ovarian cancer

Synthesis of novel 6-substituted sulfur-containing derivatives of pyridoxine

An efficient synthesis of novel 6-substituted derivatives of pyridoxine was achieved. The reactions of various thiols with mono-, bis-, and tris(hlorine) derivatives of 6-methyl-2,3,4-tris(hydroxymethyl)pyridin-5-ol (6-hydroxymethylpyridoxine) gave sulfur-containing derivatives of pyridoxine. © 2012 Elsevier Ltd. All rights reserved

Two types of adsorbed water in natural montmorillonites at low temperatures by dielectric spectroscopy

Dielectric spectroscopy was applied to natural clay mineral - montmorillonite with the exchangeable K+ and Ni2+ cations where the effect of water adsorption in the samples on the dielectric response was examined in the temperature from -115°C to -75°C and frequency from 1 Hz to 1 MHz ranges. Two relaxation processes (1 and 2) were revealed. The process 1 was related to the adsorbed ordered water structures formed on the interior surface of interlayer channels while the relaxation process 2 was attributed to the disordered water structures built between two surface water monolayers

Kinetics of the conformer reactions: II. 1 significance of media in the electrophilic addition reactions

The kinetics of electrophilic addition reaction of bromine to a multiple bond in a series of conformationally unhomogenous 2-substituted 1,3-dioxa-5-cycloheptenes was studied. We found that the compounds with trans structure are formed. The partial reaction rate constant for chair and twist forms and the reaction susceptibility parameters to the substituent electronic effect at the C2 atom are obtained. Relative reactivity of the alternative steric structures is defined by the specific solvation of the substrate. The result obtained are compared with those achieved without accounting for conformational term

Theoretical and experimental study on cyclic 6-methyl-2,3,4- tris(hydroxymethyl)pyridin-5-ol acetonides

Methods for the preparation of three cyclic 2,3,4-tris(hydroxymethyl)-6- methylpyridin-5-ol acetonides have been developed by variation of the reaction conditions. The six-membered acetonide turned out to be thermodynamically more stable than the seven-membered acetonide and bis-acetonide. The experimental data were consistent with the results of quantum-chemical calculations. The structure of the isolated compounds was proved by X-ray analysis. © 2010 Pleiades Publishing, Ltd