Novel structural analogs of isothiobarbamine, which differ from the prototype scaffold by the substituent at position 2 of the pyrimidine heterocycle, were for the first time synthesized and characterized. Data acquired in pharmacological experiments in vivo revealed that compounds 1b—d and 10 increase physical productivity, whereas compounds 1c and 10 exhibit a nootropic effect, compound 8a shows a psychostimulating effect, and compound 1b exhibits anxiolytic properties. The results reported herein indicate that the drug discovery based on new structural analogs of isothiobarbamine is promising since it may lead to drugs for the prevention and treatment of asthenia (chronic fatigue syndrome).

Synthesis of the novel Isothiobarbamine analogues with lowered basicity has been prepared. The peculiarities of their synthesis and preliminary data on their biological activity are presented.

During the synthesis of new structural analogs of isothiobarbamine, the amidoalkylation of 6-hydroxy-5-isopropyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one was found to give a mixture of mono-, di-, and trisubstituted products. Possible explanations for low regioselectivity of the reaction are given.

The Tscherniac–Einhorn reaction of 6-methyl and 6-(trifluoromethyl) derivatives of 2-thiouracil with N -(bromomethyl)phthalimide in under basic catalysis leads to the formation of S -amidomethylation products. When using 6-amino-2-thiouracil, decomposition of the alkylation products occurs. An in vitro study of the compounds obtained showed their lack of cytotoxicity and anti-HIV-1/2 activity.

Special features of the synthesis and chemical transformations of novel functional derivatives of 6-[1-(2,6-dihalophenyl)cyclopropyl]pyrimidin-4(3 H )-one and ethyl esters of 3-[1-(2,6-dihalophenyl)cyclopropyl]-2-methyl-3-oxopropanoic acids prepared from 2-(2,6-dihalophenyl)acetonitriles have been revealed. Novel achiral structural analogs of experimental anti-HIV agent МС-1501 have been synthesized.

The aminolysis of 6-[1-(2,6-difluorophenyl)cyclopropyl]-5-methyl-2-(nitroamino)pyrimidin-4(3H)-one with various amines in butan-1-ol and under solvent-free conditions is successful when the amino group in the reagent is sterically unshielded and the reaction medium is characterized by a high dielectric permittivity. Reactions of the title compound with sterically shielded amines are accompanied by alcoholysis where the amine acts as a base catalyst.

Pentapeptide analogs of somatostatin containing an (R)-1,3-thiazolidine fragment (Thz) of the general formula X-Thz-Phe-D-Trp-Lys(Y)-Thr-Z were synthesized for the first time. The synthesized compounds were tested for cytotoxic activity against three cancer cell lines (MCF-7, PC3, and HCT-116) and against human embryo fibroblasts.

New Boc-protected pentapeptide amides of the general formula Boc-Cys(Boc)-Phe-d-Trp-Lys(Boc)-Thr-NHR, which are analogs of the natural hormone somatostatin, were synthesized. The cytotoxic activity of the new compounds was evaluated against the cancer cell lines MCF-7, PC 3, and HCT-116 by the MTT test, and some of these compounds were found to exhibit activity at micromolar concentrations.

The reactions of 5-alkyl-6-(2,6-dihalobenzyl)-2-thioxo-1,2-dihydropyrimidin-4(3H)-one with 2-methyloxirane in an alkaline medium afforded uracil and 2-[(2-hydroxyprop-1yl)sulfanyl]pyrimidin-4(3H)-one derivatives. The mechanism proposed for these transformations was studied using the DFT/B3LYP/311+G** quantum chemical method, and the influence of the Nathan—Baker effect on the chemical nature and composition of the reaction products was shown.

Ethyl 5-hydroxy-1-methyl-2-(trans-2-phenylcyclopropyl)-1H-indole-3-carboxylate is the first prototype of conformationally restricted analogs of umifenovir. It has been prepared using a one-pot method and has undergone an antiviral study.

AbstractThe title compound (VI) does not exhibit any marked antiviral activity.