Zinc Complexes of Fluorosubstituted N-[2-(Phenyliminomethyl)phenyl]-4-methylbenzenesulfamides: Synthesis, Structure, Luminescent Properties, and Biological Activity.

Mono-, di-, and trifluorophenyl substituted in different positions of amine fragments bis [2-[[(E)-((fluorophenyl)iminomethyl]-N-(p-tolylsulfonyl)anilino]zinc(II) complexes were synthesized. Their crystal structure, photo- and electroluminescent properties, and protistocidal, fungistatic, and antibacterial activities were studied. It has been shown that the introduction of fluorine atoms and an increase in their number in the ligand structure of the resulting metal complexes promote the luminescence quantum yields and values of performance and brightness in EL cells compared to their previously studied chlorine-substituted analogs.

Discovery and evaluation of biphenyl derivatives of 2-iminobenzimidazoles as prototype dual PTP1B inhibitors and AMPK activators with in vivo antidiabetic activity.

This work describes the synthesis of series hydrobromides of N-(4-biphenyl)methyl-N'-dialkylaminoethyl-2-iminobenzimidazoles, which, due to the presence of two privileged structural fragments (benzimidazole and biphenyl moieties), can be considered as bi-privileged structures. Compound 7a proved to activate AMP-activated kinase (AMPK) and simultaneously inhibit protein tyrosine phosphatase 1B (PTP1B) with similar potency. This renders it an interesting prototype of potential antidiabetic agents with a dual-target mechanism of action. Using prove of concept in vivo study, we show that dual-targeting compound 7a has a disease-modifying effect in a rat model of type 2 diabetes mellitus via improving insulin sensitivity and lipid metabolism.

Synthesis, Structure, Spectral-Luminescent Properties, and Biological Activity of Chlorine-Substituted N-[2-(Phenyliminomethyl)phenyl]-4-methylbenzenesulfamide and Their Zinc(II) Complexes.

New azomethine compounds of 2-(N-tosylamino)benzaldehyde or 5-chloro-2-(N-tosylamino)benzaldehyde and the corresponding chlorine-substituted anilines, zinc(II) complexes based on them have been synthesized. The structures of azomethines and their complexes were determined by elemental analysis, IR, 1H NMR, X-ray spectroscopy, and X-ray diffraction. It is found that all ZnL2 complexes have a tetrahedral structure according to XAFS and X-ray diffraction data. The photoluminescent properties of azomethines and zinc complexes in methylene chloride solution and in solid form have been studied. It is shown that the photoluminescence quantum yields of solid samples of the complexes are an order of magnitude higher compared to the solutions and range from 11.34% to 48.3%. The thermal properties of Zn(II) complexes were determined by thermal gravimetric analysis (TGA) and differential scanning calorimetry. The TGA curves of all the compounds suggest their high thermal stability up to temperatures higher than 290 °C. The electrochemical properties of all complexes were investigated by the cyclic voltammetry method. The multilayered devices ITO/PEDOT:PSS/NPD/Zn complex/ TPBI/LiF/Al with wide electroluminescence (EL) color range spanning the range from bluish-green (494 nm) to green (533 nm) and the high values of brightness, current and power efficiency were fabricated. The biological activity of azomethines and zinc complexes has been studied. In the case of complexes, the protistocidal activity of the zinc complex with azomethine of 5-chloro-2-(N-tosylamino)benzaldehyde with 4-chloroaniline was two times higher than the activity of the reference drug toltrazuril.

Towards multi-target antidiabetic agents: Discovery of biphenyl-benzimidazole conjugates as AMPK activators.

Type 2 diabetes mellitus is a complex metabolic disorder requiring polypharmacology approaches for effective treatment. Combinatorial library of fifteen new tricyclic benzimidazole derivatives have been designed and synthesized to combine fragments commonly found in allosteric AMPK activators and AT1 receptor antagonists. It was found that 2'-cyanobiphenyl serves as the pharmacophore of AMPK-activating activity, which also increases with the expansion of the external hydrogenated cycle. Also, pronounced antiplatelet activity is characteristic of the studied compounds. One of derivatives was identified as a potent inhibitor of the formation of advanced protein glycation end-products with reactive dicarbonyl scavenging activity. Two submicromolar AMPK activators 2b and 3b prevents inflammatory activation of murine macrophages. Along with good water solubility and synthetic availability, these results render biphenyl derivatives of fused benzimidazoles as a valuable starting point for the development of AMPK activators with multi-target antidiabetic activity.

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties.

A series of derivatives of 2-hetaryl-1,3-tropolone (ß-tropolone) was prepared by the acid-catalyzed reaction of 2-methylbenzoxazoles, 2-methylbenzothiazoles and 2,3,3-trimethylindoline with 3,4,5,6-tetrachloro-1,2-benzoquinone. The molecular structures of the three representative compounds were determined by X-ray crystallography. In crystal and (as shown by the DFT PBE0/6-311+G** calculations) in solution, 2-hetaryl-4,5,6,7-tetrachloro- and 2-hetaryl-5,6,7-trichloro-1,3-tropolones exist in the NH-tautomeric form with a strong resonance-assisted intramolecular N-H···O hydrogen bond. The mechanism of the formation of 1,3-tropolones in the reaction of methylene-active five-membered heterocycles with o-chloranil in acetic acid solution has been studied using density functional theory (DFT) methods. The reaction of 2-(2-benzoxa(thia)zolyl)-5,6,7-trichloro(4,5,6,7-tetrachloro)-1,3-tropolones with alcohols leads to the contraction of the seven-membered tropone ring with the formation of 2-(2-benzoxa(thia)zolyl)-6-alkoxycarbonylphenols. The molecular structure of 2-(2-ethoxycarbonyl-6-hydroxy-3,4,5-trichlorophenyl)benzoxazole has been determined by X-ray diffraction. 2-(2-Benzoxa(thia)zolyl)-6-alkoxycarbonylphenols display intense green fluorescence with anomalous Stokes shifts caused by the excited state intramolecular proton transfer (ESIPT) effects.