161063-30-5Relevant articles and documents
Synthesis and structure of thia and selena heterocycles containing cycloamidine substructures
Fleischhauer, Jan,Beckert, Rainer,Guenther, Wolfgang,Kluge, Stefan,Zahn, Stefan,Weston, Jennie,Berg, Dorothea,Goerls, Helmar
, p. 2839 - 2848 (2007)
Cyclization of a bis-arylimidoyl chloride with an acylselenourea leads to the construction of a 1,3-selenazolidine with a heteroradialene structure. Another reaction of the bis-arylimidoyl chloride (hydrazinolysis) leads to the formation of Δ2-1,2-diazetines, which we have shown previously to be reactive precursors for ring transformation reactions that yield unusual heterocycles. We now demonstrate that the reaction of these Δ2- 1,2-diazetines with various isothio- or isoselenocyanates affords an efficient entry to highly substituted 1,3,4-thia- or -selenadiazines. The structures of these novel derivatives were confirmed by NMR and mass spectroscopy, elemental analysis, and X-ray structural analysis. Detailed multidimensional 77Se NMR experiments as well as density functional theory (DFT) calculations show structural specifics of these compounds. Georg Thieme Verlag Stuttgart.
Design, synthesis and anticonvulsant activity of new diacylthiosemicarbazides
Belenichev, I. F.,Berest, G. G.,Bukhtiayrova, N. V.,Kazunin, M. S.,Kholodniak, O. V.,Kovalenko, S. I.,Stavytskyi, V. V.
, p. 125 - 142 (2021/06/08)
Aim. A targeted search for anticonvulsant agents among unknown diacylthiosemicarbazides with the analysis of the structure-activity relationship (SAR-analysis). Methods. Organic synthesis; molecular docking; spectral methods; pentylenetetrazole convulsions, statistical methods. Results. A strategy of search for new anticonvulsant agents among unknown diacylthiosemicarbazides has been developed. It included virtual-oriented screening towards [the] active centers of enzymes and sodium channels that underlie the mechanism of antiepileptic drugs activity. The synthesis of diacylthiosemicarbazides was carried out by the in situ method, namely, accomplishing the interaction of cycloalkanecarbonyl chlorides with ammonium isothiocyanate and the subsequent nucleophilic addition of cycloalkyl-(aralkyl-, aryl-, hetaryl-) carboxylic acid hydrazides. The peculiarities of the structure of the synthesized compounds were confirmed by spectral methods (LCMS and1H NMR spectra). Biological screening showed that diacylthiosemicarbazides (2) in the experimental model of pentyleneterazole seizures in rats increased the latency period of seizures by 2.77–7.82 times, reduced the duration of tonic-clonic seizures by 1.23–5.59 minutes and prevented mortality by 30–60 %, relative to the control group of animals. It was shown that diacylthiosemicarbazides (2.6, 2.15, 2.22, 2.18) with cyclopropane-or cyclopentanecarboxamide groups show the anticonvulsant activity that exceeds that of the reference drug Depakine or competes with it. Conclusions. A range of new diacylthiosemicarbazides were obtained and the primary screening of their anticonvulsant activity was performed, the SAR-analysis was provided, and the hit-compound was identified for further in-depth pharmacological studies.
Novel N-Cycloalkylcarbonyl-N′-arylthioureas: Synthesis, Design, Antifungal Activity and Gene Toxicity
Kholodniak, Olena V.,Kazunin, Maksym S.,Meyer, Fatuma,Kovalenko, Sergiy I.,Steffens, Karl G.
, (2020/07/04)
A synthesis method of novel N-cycloalkylcarbonyl-N′-arylthioureas was developed. It consists of sequential addition of equimolecular amounts of ammonium isothiocyanate and substituted anilines to cycloalkylcarbonyl chlorides. The identity and purity of products were confirmed by LC/MS spectra, their structure by elemental analysis, IR and 1H-NMR spectra. Preliminary antimicrobial screening for standard microorganisms and molecular docking allowed to select several structures for antifungal and genetic toxicity studies. Conducted in vitro screening of 9 compounds for antifungal potential against 11 phytopathogenic fungi and three Phytophthora strains revealed that two N-(arylcarbamothioyl) cyclopropanecarboxamides at a concentration of 50 μg/ml exhibited activities comparable to the standard antifungal agent ‘Cyproconazole’. Analysis of mutagenicity of novel thioureas using the Salmonella reverse mutagenicity assay (‘Ames Test’) showed a low gene-toxicity profile.
