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Five of thiourea derivatives were prepared using as a starting compound 3-(trifluoromethyl)aniline, 4-chloro-3-nitroaniline, 1,3-thiazol-2-amine, 2H-1,2,3-triazol-4-amine and commercial isothiocyanates. All compounds were evaluated in vitro for antimicrobial activity. Derivatives 2 and 3 showed the highest inhibition against Gram-positive cocci (standard and hospital strains). The observed MIC values were in the range of 0.5-8 μg/ml. The products effectively inhibited the formation of biofilms of methicillin-resistant and standard strains of Staphylococcus epidermidis. Inhibitory activity of thioureas 2 and 3 against Staphylococcus aureus topoisomerase IV was studied. The examined compounds were nongenotoxic.

A set of arylpiperazine derivatives with imide fragments, 1-(1H-pyrrol-1-ylmethyl)-10-oxa-4-azatricyclo[5.2.1.0(2,6)-]dec-8-ene-3,5-dione connected by propyl and butyl linkers, were synthesized and tested for the potential anxiolytic and antidepressant activities. Compounds 3a and 3b demonstrated antidepressant activity in the forced swimming tests in mice and were devoid of neurotoxic effects. (chimney test in mice).

A series of 10 thiourea derivatives have been synthesized by the reaction of aromatic amine with a substituted aryl (compounds 1-3, 6-8) and alkylphenyl (4, 5, 9, 10) isothiocyanates. Their in vitro and in vivo pharmacological properties were studied. Among the evaluated compounds, two displayed very high affinity for the 5-HT2A receptor (1-0.043 nM and 5-0.6 nM), being selective over the 5-HT2C receptor. Derivatives 3, 5, 9, 10 by 70-89% diminished L-5-HTP-induced head twitch episodes. Compounds 1 and 5 as the 5-HT2A receptor antagonists produced a dose-dependent decrease in the number of DOI-elicited HTR. Compounds 1-5 strongly reduced amphetamine-evoked hyperactivity in rodents. In another test, 1 and 2 caused hyperthermia in mice, whereas 9 and 10 led to hypothermia. Antinociceptive and anticonvulsant properties of selected derivatives were demonstrated. Molecular docking studies using a homology model of 5-HT2A revealed a significant role of hydrogen bonds between both thiourea NH groups and Asp155/Tyr370 residues, as well as π-π interaction with Phe339., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

A series of halogeno derivatives of thiourea bearing a polycyclic imide core has been efficiently synthesized and evaluated for antimicrobial activity. The structures of the compounds were established by 1H and 13C NMR and MS methods. The molecular structure of 4Clc was determined by an X-ray crystallography. Compounds containing 3-chloro-4-fluorophenyl substituent (3Cl4Fb, 3Cl4Fd) were found to be the most promising against Gram-positive bacteria (MIC values ranged from 8 to 32 pg/mL for standard and 32 - 64 µg/mL for hospital strains). The in vitro cytotoxicity against MT-4 cells of all compounds was evaluated.

A total of 31 of thiourea derivatives was prepared reacting 3-(trifluoromethyl)aniline and commercial aliphatic and aromatic isothiocyanates. The yields varied from 35% to 82%. All compounds were evaluated in vitro for antimicrobial activity. Derivatives 3, 5, 6, 9, 15, 24 and 27 showed the highest inhibition against Gram-positive cocci (standard and hospital strains). The observed MIC values were in the range of 0.25-16 μg/ml. Inhibitory activity of thioureas 5 and 15 against topoisomerase IV isolated from Staphylococcus aureus was studied. Products 5 and 15 effectively inhibited the formation of biofilms of methicillin-resistant and standard strains of Staphylococcus epidermidis. Moreover, all obtained thioureas were evaluated for cytotoxicity and antiviral activity against a large panel of DNA and RNA viruses. Compounds 5, 6, 8-12, 15 resulted cytotoxic against MT-4 cells (CC50 ≤ 10 μM)., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The preparation of 16 derivatives of 3,5,8-trioxo-4-azatricyclo- [5.2.2.0(2.6)]undec-1-yl acetate and 8 derivatives of 1-isobutoxy-4-azatricyclo[5.2.2.0(2.6)]undecane-3,5,8-trione was described. Substituents to the imide N-atom were alkyl-(aryl)piperazine fragments with an alkyl linker being propyl or butyl group. Selected newly obtained compounds were evaluated in vitro against anti-HIV-1 activity. A broad group o fderivatives were tested for their antibacterial and antifungal activity. The pharmacological properties of butyl derivatives of imide 6 were evaluated in three behavioral tests in mice. The molecular structures of starting polycyclic 6-acetyl-imides, 1 and 5, were determined by X-ray crystallography. Presented tests have not revealed any activity of the compounds, however, selected derivatives exerted no neurotoxicity in behavioral tests.

An overview of docking models of chain arylpiperazines to different subtypes of serotonin receptors belonging to the GPCR family is presented. The theory of a ligand-receptor interaction has been briefly summarized. The review covers more than twenty models, beginning with the early models of a ligand interaction with the 5-HT1A and 5-HT2A receptor, and ending with a ligand-5-HT7 receptor docking studies.

The present paper discusses models of 5-HT(1A) and 5-HT(2A) receptors, developed by conformational analysis and 3D-QSAR methods. Hypotheses concerning the ligand-5-HT(7) receptor interaction were complemented by models constructed on the basis of the receptor's structure. Various pharmacophore concepts are supported by structures of exemplary ligands and groups of compounds, derived from chain polycyclic arylpiperazines, used for models generations.

In the title compound, C20H17NO3 (alternative name: N-hy-droxy-9,10-dimethyl-9,10-ethano-anthracene-11,12-dicarboximide), the rigid ethano-anthracene-dicarboximide moiety has a roof-shaped geometry, the inter-planar angle between the two terminal phenyl rings being 124.9 (6)°. In the crystal, mol-ecules are linked via O-H⋯O hydrogen bonds, forming chains along [010]. C-H⋯O and C-H⋯π inter-actions link adjacent chains, leading to the formation of a three-dimensional structure.

The title mol-ecule, C(8)H(6)BrNS(2), is almost planar with a dihedral angle of 0.9 (1)° between the benzene and thia-zole rings. The values of the geometry-based index of aromaticity (HOMA) and the nucleus-independent chemical shift (NICS) for the two cyclic fragments of the title mol-ecule are 0.95 and -9.61, respectively, for the benzene ring, and 0.69 and -7.71, respectively, for the thia-zole ring. They show that the benzene ring exhibits substanti-ally higher cyclic π-electron delocalization than the thia-zole ring. Comparison with other similar benzothia-zole fragments reveals a similar trend.

The title compound, C(10)H(12)FN(3)S, crystallizes in the same space group (P2(1)/c) as two polymorphic forms of 4-phenyl-1-(propan-2-yl-idene)thio-semicarbazone [Jian et al. (2005). Acta Cryst. E61, o653-o654; Venkatraman et al. (2005). Acta Cryst. E61, o3914-o3916]. The arrangement of mol-ecules relative to the twofold screw axes is similar to that in the crystal structure of the lower density polymorph. In the solid state, the mol-ecular conformation is stabilized by an intra-molecular N-H⋯N hydrogen bond. The mol-ecules form centrosymmetric R(2) (2)(8) dimers in the crystal through pairs of N-H⋯S hydrogen bonds.

Antibacterial and antifungal activity of 2,4-dihydro- [1,2,4]triazol-3-one derivatives were examined by the disc-diffusion method (growth inhibition zone diameter in agar medium). The MIC's for the most active agents were determined. Of all the tested compounds, aminomethyl derivatives of 2,4-dihydro-[1,2,4]triazol-3-one exhibit activity against the majority of microorganisms studied.

A series of aminoalkanol derivatives of 4-hydroxy-1,7,8,9,10-pentamethyl-4-aza-tricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione have been prepared. The pharmacological profile of selected compounds was evaluated for their affinities at beta-adrenoreceptors.

3-(Oxiran-2-ylmethoxy)-l ,5-diphenyl-lH-1,2,4-triazole [I] was obtained in the reaction of 1,5-di-phenyl-IH-1,2,4-triazol-3-ol with 2-(chloromethyl) oxirane. Then I was converted into the corresponding aminoalkanol derivatives of 1,5-diphenyl-IH-1,2,4-triazol-3-ol, IIa,b -VIIa,b. Molecular structure of I was confirmed by an X- ray structure analysis. The receptor affinities for IVa, VIIa were determined.

A series of new derivatives of isoindole in the reaction of nucleophilic substitution with ethyl chloroformate, ethyl bromoacetate and ethyl 3-bromopropanoate were synthesized.

In the reaction of (4-phenyl- or 3,4-diphenyl-5-oxo-1,2,4-triazeolin-1-ylmethyl)-carbohydrazide (IIa, IIb) with isothiocyanates the thiosemicarbazide derivatives [IIIa, b - IXa, b] were obtained. Cyclization of those compounds in the presence of 2% or 10% NaOH led to formation of derivatives with the 1,2,4-triazolin-5-thione system [Xa, b - XV[a, b]. Molecular structure proposed for this group of compounds was confirmed by X-ray structure analysis of Xa and XIVa. Compounds Xa, XIIa and XIVa were investigated pharmacologically for their central properties in mice. It was shown that only compound XIIa produced antinociceptive effects in mice.