Antiviral Drugs in Influenza

Flu is a serious health, medical, and economic problem, but no therapy is yet available that has satisfactory results and reduces the occurrence of these problems. Nearly 20 years after the registration of the previous therapy, baloxavir marboxil, a drug with a new mechanism of action, recently appeared on the market. This is a promising step in the fight against the influenza virus. This article presents the possibilities of using all available antiviral drugs specific for influenza A and B. We compare all currently recommended anti-influenza medications, considering their mechanisms of action, administration, indications, target groups, effectiveness, and safety profiles. We demonstrate that baloxavir marboxil presents a similar safety and efficacy profile to those of drugs already used in the treatment of influenza. Further research on combination therapy is highly recommended and may have promising results

Eco-friendly methods of synthesis and preliminary biological evaluation of sulfonamide derivatives of cyclic arylguanidines

The chemotype of arylsulfonamide derivatives of cyclic arylguanidines is a source of molecules with valuable biological activities, including antimicrobial and antitumor properties. The methods of the synthesis presented in the literature are characterized with low selectivity and high environmental nuisance. In this publication, we present a developed alternative and earlier undescribed pathway C, for the synthesis of arylsulfonamide derivatives of cyclic arylguanidines (N-(1H-arylimidazol-2-yl)arylsulfonamides and N-(1,4-dihydroquinazolin-2-yl)arylsulfonamides), including reaction between 2-(methylsulfanyl)-benzimidazole or 2-(methylsulfanyl)-3,4-dihydroquinazoline with arylsulfonamides. We also optimized previously reported methods; A (reaction of 2-aminobenzimidazole or 2-amino-3,4-dihydroquinazoline with arylsulfonyl chlorides) and B (reaction of dimethyl-(arylsulfonyl)carbonodithioimidate with aryldiamines). The conducted research allowed achieving two independent ecological and quick methods of obtaining the desired products. We used ecological methods of ultrasound-assisted or microwave synthesis, solvent-free reactions and a “green” reaction environment. In both pathways, it has proven advantageous to use H(2)O as the solvent and K(2)CO(3) (1 or 3 equivalent) as the basic agent. In the sonochemical variant, the efficiency reached B: 37–89 %, C: 90 % in 60 min (P = 80 W and f = 40 kHz), while in the microwave synthesis it was B: 38–74 %, C: 63–85 % in 0.5–4 min (P = 50 W). Path A led to a complementary substitution product (i.e. 1-(arylsulfonyl)-1H-benzimidazol-2-amine or 1-(arylsulfonyl)-1,4-dihydroquinazolin-2-amine). We obtained a small group of compounds that were tested for cytotoxicity. The 10f (N-(1,4-dihydroquinazolin-2-yl)naphthalene-1-sulfonamide) showed cytotoxic activity towards human astrocytoma cell line 1321 N1. The calculated IC(50) value was 8.22 µM at 24 h timepoint (doxorubicin suppressed 1321 N1 cell viability with IC(50) of 1.1 µM). The viability of the cells exposed to 10f for 24 h dropped to 48.0 % compared to vehicle control, while the cells treated with doxorubicin experienced decline to 47.5 %. We assessed its potential usefulness in pharmacotherapy in the ADMET study, confirming its ability to cross the blood–brain barrier (Pe = 5.0 ± 1.5 × 10(-6) cm/s) and the safety of its potential use in terms of DDI and hepatotoxicity

New Pharmaceutical Salts of Trazodone

New pharmaceutically acceptable salts of trazodone (trazodone hydrogen bromide and trazodone 1-hydroxy-2-naphthonic acid) for the treatment of central nervous system disorders are synthesized and described. Although trazodone salts are poorly crystalline, single-crystal X-ray diffraction data for trazodone 1-hydroxy-2-naphthonic acid were collected and analyzed as well as compared to the previously described crystal structure of commercially available trazodone hydrochloride. The powder samples of all new salts were characterized by Fourier transform infrared spectroscopy, X-ray diffraction and 13C solid-state nuclear magnetic resonance spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of carbon chemical shielding constants. The main goal of our research was to find salts with better physicochemical properties and to make an attempt to associate them with both the anion structure and the most prominent interactions exhibited by the protonated trazodone cation. The dissolution profiles of trazodone from tablets prepared from various salts with lactose monohydrate were investigated. The studies revealed that salts with simple anions show a fast release of the drug while the presence of more complex anion, more strongly interacting with the cation, effects a slow-release profile of the active substance and can be used for the preparation of the tables with a delay or prolonged mode of action

Coordination modes of 2-mercapto-1,3-benzothiazolate in gallium and indium complexes

<p>2-Mercapto-1,3-benzothiazole (mbztH) may act as a chelating or bridging ligand. In this study, reactions of mbztH with Me₃Ga and Me₃In were examined. The products were characterized by NMR spectroscopy, elemental analyses, melting point, and molecular weight determinations. Formation of mononuclear chelating complexes Me₂M(mbzt) (M = Ga, In) was observed in solutions. Crystallization of Me₂M(mbzt) yielded uncommon non-symmetrical dinuclear complexes Me₄M₂(mbzt)₂, in which one metal is bonded to two sulfurs and the other to two nitrogens.</p

Mechanochemical Synthesis Method for Drugs Used in the Treatment of CNS Diseases under PTC Conditions

Phase transfer catalysis (PTC) is an excellent possibility in the synthesis of organic compounds as it allows the reactions to be carried out under the conditions of green chemistry, while maintaining high yields and selectivity. The great advantage of these reactions is also the possibility of carrying out the reactions not only under conventional conditions, but also mechanochemically in solvent-free processes. Bearing this in mind, we decided to develop a new method for the synthesis of known biologically active compounds from the group of long-chain arylpiperazines (LCAPs). The first mortar trials were very promising and prompted us to carry out a series of ball mill reactions. One of the technological problems that we encountered while conducting reactions in the ball mill was the difficulty in extracting the post-reaction mixture. We tested the effects of additives improving the insulation of the product, such as, e.g., starch, zeolites, and silica. Research has proven that with appropriate process conditions using TBAB as a catalyst and in the presence of potassium carbonate and a small amount of Zeolite ZSM5 or silica, aripiprazole can be obtained with a yield of 90% in just five minutes. The obtained results are very promising and it is worth considering them as an alternative to the synthesis of other compounds from the LCAPS group

Mechanochemical Synthesis Method for Drugs Used in the Treatment of CNS Diseases under PTC Conditions

Phase transfer catalysis (PTC) is an excellent possibility in the synthesis of organic compounds as it allows the reactions to be carried out under the conditions of green chemistry, while maintaining high yields and selectivity. The great advantage of these reactions is also the possibility of carrying out the reactions not only under conventional conditions, but also mechanochemically in solvent-free processes. Bearing this in mind, we decided to develop a new method for the synthesis of known biologically active compounds from the group of long-chain arylpiperazines (LCAPs). The first mortar trials were very promising and prompted us to carry out a series of ball mill reactions. One of the technological problems that we encountered while conducting reactions in the ball mill was the difficulty in extracting the post-reaction mixture. We tested the effects of additives improving the insulation of the product, such as, e.g., starch, zeolites, and silica. Research has proven that with appropriate process conditions using TBAB as a catalyst and in the presence of potassium carbonate and a small amount of Zeolite ZSM5 or silica, aripiprazole can be obtained with a yield of 90% in just five minutes. The obtained results are very promising and it is worth considering them as an alternative to the synthesis of other compounds from the LCAPS group

Substituent and Solvent Effects on Intermolecular Interactions in Crystals of <i>N</i>‑Acylhydrazone Derivatives: Single-Crystal X‑ray, Solid-State NMR, and Computational Studies

New crystalline forms of hydrated and anhydrous <i>N</i>-acylhydrazones are reported. The studied crystal structures were determined by single-crystal X-ray diffraction at 90 or 100 K. Transferred aspherical atom model (TAAM) structure refinements were performed with the aid of the most recent version of the University at Buffalo Databank (UBDB). The resulting crystal structures were analyzed in terms of molecular conformations, intermolecular interaction energies, and crystal packing motifs. For this purpose, solid-state NMR studies and theoretical calculations were conducted supplementarily. It was found that all studied hydrazones adopt the <i>E</i> configuration around the azine N–N bond and imino NC function in the solid state, whereas the hydrazide N–N–CO moiety exhibits the <i>E</i> and <i>Z</i> arrangement in the <i>N</i>-acyl and <i>N</i>-aroyl derivatives, respectively. The constrained energy scans confirmed the <i>E</i> conformation of the hydrazide unit and the <i>E</i> arrangement of pyridine and hydrazone N atoms as the most stable ones. The association modes in the studied crystals are dominated by strong hydrogen bonds of the N–H···O or N–H···N-type involving the amide group as a proton donor. Consequently, as indicated by lattice energy calculations, a significant increase in the crystal cohesive energy per asymmetric unit is observed when water molecules are incorporated into the crystal structure, because this enables efficient saturation of the hydrogen bond acceptor and donor atoms. On the other hand, a substantial contribution of π···π stacking interactions to the overall stabilization of the crystal nets was also found. Thus, when more bulky phenyl substituents are introduced, the cohesive energy becomes more favorable