V. P. Lezina

Synthesis and antidepressant and anxiolytic activity of derivatives of pyrazolo[4,3-c]pyridine and 4-phenylhydrazinonicotinic acids

The synthesis of compounds effective in the treatment of anxiety—depression disorders is described. It is established that 4,6-dimethyl-2-(4-chlorophenyl)-2,3-dihydro-1H-pyrazolo[4,3-c]pyridine-3-one hydrochloride (IVa) possesses combined antidepressant and anxiolytic properties. Advantages of IVa are low toxicity and the absence of side effects typical of antidepressants (elevated anxiety) and benzodiazepine anxiolytics (myorelaxant and sedative action).

Nitration of 2- and 5-benzyl-3-hydroxypyridines and their N-oxides

The nitration of 2- and 5-benzyl-3-hydroxpyridines and their N-oxides takes place in the para position of the phenyl ring. The introduction of an N-oxide group into the Β-pyridol ring does not affect the orientation of substitution.

Imine-enamine tautomerism of tropanone Schiff's bases

Using PMR spectroscopy, we have demonstrated the existence of an imine-enamine tautomerism and optically active forms in tropanone Schiffs bases. We have studied the effect of solvents and substituents on the tautomeric equilibrium of the system. By reaction with acid chlorides, we obtain the N-acylation products of the enamine form of the Schiffs bases.

4-Methyl-5-hydroxypyrimidine and its N-oxides: Synthesis and investigation of the reactivities in electrophilic substitution

A new more accessible method for the synthesis of 4-methyl-5-hydroxypyrimidine is proposed; its 1- and 3-oxides were obtained. An attempt was made to evaluate the reactivities of the individual positions of the heterocyclic ring of pyrimidine and its 3-oxide in aminomethylation.

Investigation of the acid- and base-induced transformations of nitrogen heterocycles by NMR spectroscopy. 1. Substituted pyridines and pyrimidines

The principles of the changes in the chemical shifts of the protons of substituted pyridines, pyrimidines, 3-hydroxypridines, and 5-hydroxypyrimidines as a function of the basicity of the medium were investigated. The ionization constants and the possible forms of existence of the molecules were determined. The character of the effect of substituants (alkyl and hydroxy groups) on the basicities of the investigated compounds was ascertained. A spectral parameter that correlates satisfactorily with the pKa values is proposed.

Synthesis of 3-(2-aryloxazolidin-3-yl)tropanes

We obtained 3-(2-aryloxazolidin-3-yl)tropanes by reaction of aromatic aldehydes with 3-[N-(2-hydroxyethyl)amino]tropane. We obtained 3-benzyloxazolidine-2-spiro-3-(8-carbethoxy)nortropane by reaction of benzylaminoethanol with 8-carbethoxynortropan-3-one.

Investigation of acid deuterium exchange in a number of isoquinoline and 4-hydroxyisoquinoline derivatives

The acid deuterium exchange of isoquinoline and 4-hydroxy- and 3-methyl-4-hydroxyisoquinolines at 145°C in 94% D2SO4 was investigated by PMR spectroscopy. The sequence of substitution and the rate constants for deuterium exchange of the protons of the isoquinoline ring were determined. The most reactive protons in isoquinoline and 3-methyl-4-hydroxyisoquinoline are those of the benzene ring, while the proton in the 3 position of the β-pyridol ring is the most reactive in 4-hydroxyisoquinoline.

Developing analytical methods for the creation of the state reference sample of noopept

The physicochemical properties of noopept, a new domestic original drug with nootropic action, have been studied with a view to developing analytical methods, establishing quality criteria for the parent drug substance, and creating the state reference sample (SRS). These methods will be included in a draft of the regulation on the SRS of noopept.

Development of analytical methods for hydrochloride salts of cardiocyclide, a new Russian class III antiarrhythmic

Cardiocyclide, a new Russian class III antiarrhythmic agent, was developed at the State V. V. Zakusov Science Research Institute Pharmacology, Russian Academy of Medical Sciences. The aims of the present work were to study the physicochemical properties of the hydrochloride salt of this agent (N1-(3-diethylaminopropyl)-N1-(p-nitrobenzoyl)aminoacetic acid N,N-dicyclohexylamide HCl) and to develop an analytical method for this compound. IR, 1H NMR, and UV spectra were obtained for cardiocyclide; its solubility was studied; its melting temperature, weight loss on drying and the transparency, color, and pH of its solutions were determined. The purity of material containing compound I was determined by thin-layer chromatography; quantitative cardiocyclide contents were estimated by non-aqueous titration.

Synthesis, conformation analysis, and anxiolytic activity of retropeptide analogs of 4-cholecystokinin

Potential dipeptide anxiolytics with the general formula Ph(CH2)5 CO-X-L-Trp-NH2(X = Gly, β-Ala, GABA, L-Pro) have been synthesized on the basis of the 4-cholecystokinin structure. These compounds exhibit anxiolytic activity in the elevated plus-maze test in rats at doses of 0.01–0.5 mg/kg (i.p.). The activity among these derivatives increases in the following order: GABA → β-Ala → Gly → Pro. Conformation analysis of dipeptides in solution by 1H NMR method with the use of the nuclear Overhauser effect and peptide vicinal 3J(H-NCα-H) coupling constants has been carried out. It is established that the percentage of βI-turn conformation stabilized by hydrogen bonds with the participation of C-end amide group proton also increases in the order β-Ala → Gly → Pro derivatives. It is concluded that the βI-turn conformation is probably the biologically active one in the synthesized substituted dipeptides.