The stereoselective synthesis of 1,2,3-triol derivatives having contiguous stereogenic centers from alpha,beta-unsaturated acylsilanes 1 was described. The oxidation of an olefin moiety of 1 with ...osmium tetroxide proceeded smoothly to give the corresponding 2,3-syn-dihydroxyacylsilanes 2. The protection of two hydroxy groups of 2 followed by a nucleophilic reaction to the silyl carbonyl group gave the corresponding silylated triol derivatives (7 and 8) with high stereoselectivity, depending on the kind of nucleophilic reagents. The deprotection for 7 and 8 and the following protodesilylation gave two isomers of possible four 1,2,3-triol derivatives. The stereoselective triol synthesis by asymmetric diolization of alpha-silylated allyl alcohols 11 derived by nucleophilic addition to 1 was also investigated.
Most of the anti-inflammatory drugs in clinical practice are becoming outdated owing to their potential side and adverse effects. These are found to be highly unsafe for long term use. Thus, since ...last few years, new anti-inflammatory agents are being developed and number of them are in advanced stages of clinical trials. Heterocyclic molecules have gained great attention of chemists due to their similarity to different biological precursors. In the current review, we have highlighted the recent developments (2015 onwards) in designing and synthesis of various heterocyclic anti-inflammatory molecules along with detailed SAR studies. The principal objective of this review is to provide a profound overview of the recently explored heterocyclic anti-inflammatory agents belonging to various classes such as pyrazole, pyrimidine, benzimidazole, indole, and other related heterocyclic compounds. In addition, an enlarged view on potential interactions of synthetic preparations with target inflammatory enzymes or cytokines has been provided. We have also enlisted lead compounds undergoing different clinical trials against inflammation. The elementary aim of this review is to provide restructured knowledge regarding heterocyclic molecules which will be valuable for the scientists working in the field of anti-inflammatory chemistry. The authors believe that lead compounds mentioned in the report will help to design and develop novel anti-inflammatory drug molecules targeting various factors involved in the progression of inflammation.
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•This review is focused on the recent developments in heterocyclic anti-inflammatory agents (2015 onwards).•Anti-inflammatory agents bearing different heterocyclic moieties are discussed.•The SAR of newly synthesized derivatives is explained for understanding designing strategies.•This review may help medicinal chemists to design and develop novel anti-inflammatory drug molecules.
The use of alternative energy sources, such as microwaves (MW) or ultrasounds (US), and their mutual cross-combination have been widely described in the literature in the development of new synthetic ...methodologies in organic and medicinal chemistry. In this review, our attention is focused on representative examples, reported in the literature in the year range 2013-2023 of selected N-containing bicyclic heterocycles, with the aim to highlight the advantages of microwave- and ultrasound-assisted organic synthesis.
•Structural changes on the scaffold of interest affected in vitro liver cytotoxicity.•Higher toxicity was observed in the more metabolically competent cell line.•A safety profile for the compounds ...was derived using activity and toxicity data.
2-Phenylaminophenylacetic acid is a widely-exploited chemical scaffold whereby notable NSAIDs such as diclofenac and lumiracoxib were derived. Yet, their clinical usage has been associated with toxicities in the liver. While some studies have attributed toxicities to the bioactivation of both drugs to reactive intermediates, the structural predisposition for toxicity, as well as relationship between this toxicity and COX inhibitory activity has not been elucidated. In this study, we aimed to address their intricate link by synthesizing compounds that possess the 2-phenylaminophenylacetic acid backbone with varying alkyl and halogen substituents at three positions critical to the COX inhibitory pharmacophore. These compounds were subjected to cytotoxicity testing on two liver cell lines of contrasting metabolic competencies. We observed higher toxicity in the more metabolically competent cell line, supporting the role of bioactivation as a prerequisite for toxicity. We have also shown that structural changes on the chemical scaffold exerted pronounced effect on liver cytotoxicity. The most lipophilic and brominated compound (24) was identified as the most cytotoxic of all the compounds. A concurrent determination of their pharmacological activity using COX inhibition assays allowed us to derive a safety profile, which showed that selectivity towards COX-2 negatively affected activity and toxicity.
γ-Aminopropylsilatrane has been reported to possess biological activity against tumor cancer cells with low cytotoxicity in many kinds of silatranes. So some N-substituted γ-aminopropylsilatrane ...derivatives were synthesized and assayed by a primary anticancer screening against HT-29, Hela, and MDAMB435 cells by the use of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The structures of these derivatives were confirmed by 1H NMR, electrospray ionization-mass spectrometry, and elemental analysis. The structure-activity relationship showed that the N-substituted derivatives exhibit better activity in which the γ-amino group of the silatrane is connected with stronger electron-withdrawing groups. PUBLICATION ABSTRACT
The thermotropic properties and self-assembly of two different series of hexa-peri-hexabenzocoronenes (HBC) bearing either linear or branched perfluoroalkylated side chains, each with a wide range of ...alkyl spacer and perfluorinated tail lengths, have been studied. Correlations between thermogravimetric analysis, differential scanning calorimetry, polarised optical microscopy and small-angle X-ray scattering experiments revealed, as expected, that the transition temperatures and phase stability are influenced by the determining roles of the aliphatic spacer length and odd/even nature, as well as the size and structure (linear vs. bifurcation) of the perfluorinated sections. Most of the investigated HBC derivatives showed a single-column hexagonal columnar phase, where the columns are structured by a double segregation process between HBC aromatic cores and aliphatic spacers, on the one hand, and between aliphatic spacers and fluorinated tails, on the other hand. For the derivatives with long linear spacers, cores of untilted or quasi-untilted HBC stacks are surrounded by a cylindrical aliphatic envelope segregated from the fluorinated periphery, whereas for those with shorter linear spacers, the same structure is kept, except that the aliphatic envelope deviates from cylindricality and causes a symmetry break to rectangular envelope for the first term of the series. Of the four HBC with branched spacers, two are amorphous, whereas a columnar phase is maintained for the other two derivatives, but with tilted HBC stacks. Consequently, the evolution of the polymorphism in the series could be correlated with the variation of both interface areas. PUBLICATION ABSTRACT
An expanded family of ruthenium‐based metathesis catalysts bearing cyclic alkyl amino carbene (CAAC) ligands was prepared. These catalysts exhibited exceptional activity in the ethenolysis of the ...seed‐oil derivative methyl oleate. In many cases, catalyst turnover numbers (TONs) of more than 100 000 were achieved, at a catalyst loading of only 3 ppm. Remarkably, the most active catalyst system was able to achieve a TON of 340 000, at a catalyst loading of only 1 ppm. This is the first time a series of metathesis catalysts has exhibited such high performance in cross‐metathesis reactions employing ethylene gas, with activities sufficient to render ethenolysis applicable to the industrial‐scale production of linear α‐olefins (LAOs) and other terminal‐olefin products.
A new series of olefin‐metathesis catalysts containing cyclic alkyl amino carbene (CAAC) ligands exhibit unprecedented activity in the ethenolysis of methyl oleate. This work advances the state‐of‐the‐art of the ethenolysis reaction and is expected to find particular use in large‐scale industrial applications.
Metal halide perovskites and derivatives exhibit a high sensitivity and low detection limit as direct X‐ray detectors. Inorganic 2D bismuth halide perovskites are promising for X‐ray detections, but ...have not been reported. Moreover, the quantitative relationship between the structural dimensionality of A3B2X9 perovskites and their compositions has never been investigated, and the underlying mechanism is unclear. Here, the key structural descriptors for 2D A3B2X9 perovskite derivatives are reported: i) octahedral factor μ, 0.377 < μ < 0895; ii) tolerance factor t, 0.8 < t < 1.06; iii) (rA‐0.55)/t < 1.48 Å. Accordingly, a new 2D A3B2X9 perovskite derivative, Rb3Bi2I9, with high X‐ray attenuation coefficients is found. The assembled X‐ray detector exhibits a high μτ product of 2.51 × 10−3 cm2 V−1, good sensitivity for 159.7 μC Gyair−1 cm−2, and a record low detection limit of 8.32 nGyair s−1 among all direct and indirect perovskite X‐ray detectors. The device also exhibits good stability toward external bias and continuous gamma ray radiations (480 000 Gy). This work provides crystal structural insights to rationally design 2D perovskites for new types of radiation detectors.
The key structural descriptors are reported for 2D A3B2X9 perovskite derivatives. By following the above designing rules, Rb3Bi2I9 is assembled into an X‐ray detector, exhibiting a low detection limit of 8.32 nGyair s−1 and suppressed ions migration. The inorganic composition also guarantees excellent stability toward continuous radiation from the 60Co source.
We examine the effects of new regulations introduced by Korean government to cool down overheated Korean ELW markets. We also investigate whether ELWs are fairly priced as noted in the previous ...research. The empirical findings are as follows. Firstly, ELW was more expensive than KOSPI200 option not only before but also after the introduction of the new regulations. But degrees of the overpricedness are decreased significantly with the new regulations. Secondly, we confirm the well known facts in the literature that liquidity providers get extra profits as monopolistic providers for ELWs. Thirdly, we analyze the determinants of the differences in premiums between ELW and KOSPI200 option. The trading volume is negatively correlated with premium difference, however, timeto-maturity and market share are not statistically significant. Even though it seems that the financial regulator achieve their primary purpose to control the overheated market, we find that the new regulations have almost no effects on the overpricing problem, which implies that overpricing in ELW is not related to the market inefficiency.
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