2-(2-(Fluorosulfonyloxy)phenyl)benzoxazole

Jin X., Ma X., Zhong W., Cao Y., Zhao H., Leng X., Yang J., Zhou H., She M.

Specifically, visually, and quantitatively monitor copper ion (Cu2+) is critical in the area of biological and environmental detection. Herein, a ratiometric fluorescent probe with benzoxazole appended xanthenes skeleton was constructed and further employed to monitor Cu2+ in Hela cells, real water samples, and test strips. An easily distinguishable colorimetric (colorless to red) and fluorescence (green to red) change could be observed by naked eye under the portable UV lamp (365 nm) and the changes could be recovered by adding S2−. Furthermore, electrospinning technique was employed to fabricate a probe composited fluorescent sensing film (PMMA) for realizing the visual and recyclable monitoring of Cu2+, indicating that the probe-composited fluorescent sensing film has great potential for on-site and naked-eye detection of Cu2+ in practical.

Ghoshal T., Patel T.M.

According to the report published recently by the World Health Organization, the number of cancer cases in the world will increase to 22 million by 2030. So the anticancer drug research and development is taking place in the direction where the new entities are developed which are low in toxicity and are with improved activity. Benzoxazole and its derivative represent a very important class of heterocyclic compounds, which have a diverse therapeutic area. Recently, many active compounds synthesized are very effective; natural products isolated with benzoxazole moiety have also shown to be potent towards cancer. In the last few years, many research groups have designed and developed many novel compounds with benzoxazole as their backbone and checked their anticancer activity. In the review article, the recent developments (mostly after 2015) made in the direction of design and synthesis of new scaffolds with very potent anticancer activity are briefly described. The effect of various heterocycles attached to the benzoxazole and their effect on the anticancer activity are thoroughly studied and recorded in the review. These compiled data in the article will surely update the scientific community with the recent development in this area and will provide direction for further research in this area.

Barrow A.S., Smedley C.J., Zheng Q., Li S., Dong J., Moses J.E.

SuFEx (Sulfur Fluoride Exchange) is a modular, next generation family of click reactions, geared towards the rapid and reliable assembly of functional molecules.

Singh S., Veeraswamy G., Bhattarai D., Goo J., Lee K., Choi Y.

In recent years, the emergence of biologically active compounds that contain a heterocyclic ring has gained a great deal of attention among medicinal chemists. Among these, benzoxazole-based compounds are particularly attractive because of their wide range of pharmacological activities. In this focus review, we highlight recent advancements in the development of benzoxazole-based pharmacologically active compounds since the year 2000.

Demmer C.S., Bunch L.

The benzoxazole heterocycle is often found in ligands targeting a plethora of receptors and enzymes. By analysis of published X-ray structures, this review aims at highlighting key interactions which the benzoxazole may engage in with its host protein. Furthermore, bioavailability, metabolism and the use of benzoxazole as a bioisostere are discussed. The review is extended to cover structure-activity relationship studies of 2-substituted benzoxazoles, 2-substituted oxazolopyridines, and in perspective, application of the recently published novel heterocycle oxazolopyrazine in medicinal chemistry studies.

Dong J., Krasnova L., Finn M.G., Sharpless K.B.

AbstractAryl sulfonyl chlorides (e.g. Ts‐Cl) are beloved of organic chemists as the most commonly used SVI electrophiles, and the parent sulfuryl chloride, O2SVICl2, has also been relied on to create sulfates and sulfamides. However, the desired halide substitution event is often defeated by destruction of the sulfur electrophile because the SVICl bond is exceedingly sensitive to reductive collapse yielding SIV species and Cl−. Fortunately, the use of sulfur(VI) fluorides (e.g., R‐SO2‐F and SO2F2) leaves only the substitution pathway open. As with most of click chemistry, many essential features of sulfur(VI) fluoride reactivity were discovered long ago in Germany.6a Surprisingly, this extraordinary work faded from view rather abruptly in the mid‐20th century. Here we seek to revive it, along with John Hyatt’s unnoticed 1979 full paper exposition on CH2CH‐SO2‐F, the most perfect Michael acceptor ever found.98 To this history we add several new observations, including that the otherwise very stable gas SO2F2 has excellent reactivity under the right circumstances. We also show that proton or silicon centers can activate the exchange of SF bonds for SO bonds to make functional products, and that the sulfate connector is surprisingly stable toward hydrolysis. Applications of this controllable ligation chemistry to small molecules, polymers, and biomolecules are discussed.

Epstein L.F., Chen H., Emkey R., Whittington D.A.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that, when genetically altered by mutation, amplification, chromosomal translocation or inversion, has been shown to play an oncogenic role in certain cancers. Small molecule inhibitors targeting the kinase activity of ALK have proven to be effective therapies in certain ALK-driven malignancies and one such inhibitor, crizotinib, is now approved for the treatment of EML4-ALK-driven, non-small cell lung cancer. In neuroblastoma, activating point mutations in the ALK kinase domain can drive disease progression, with the two most common mutations being F1174L and R1275Q. We report here crystal structures of the ALK kinase domain containing the F1174L and R1275Q mutations. Also included are crystal structures of ALK in complex with novel small molecule ALK inhibitors, including a classic type II inhibitor, that stabilize previously unobserved conformations of the ALK activation loop. Collectively, these structures illustrate a different series of activation loop conformations than has been observed in previous ALK crystal structures and provide insight into the activating nature of the R1275Q mutation. The novel active site topologies presented here may also aid the structure-based drug design of a new generation of ALK inhibitors.

Xing L., McDonald J.J., Kolodziej S.A., Kurumbail R.G., Williams J.M., Warren C.J., O’Neal J.M., Skepner J.E., Roberds S.L.

Structure-based virtual screening was applied to design combinatorial libraries to discover novel and potent soluble epoxide hydrolase (sEH) inhibitors. X-ray crystal structures revealed unique interactions for a benzoxazole template in addition to the conserved hydrogen bonds with the catalytic machinery of sEH. By exploitation of the favorable binding elements, two iterations of library design based on amide coupling were employed, guided principally by the docking results of the enumerated virtual products. Biological screening of the libraries demonstrated as high as 90% hit rate, of which over two dozen compounds were single digit nanomolar sEH inhibitors by IC(50) determination. In total the library design and synthesis produced more than 300 submicromolar sEH inhibitors. In cellular systems consistent activities were demonstrated with biochemical measurements. The SAR understanding of the benzoxazole template provides valuable insights into discovery of novel sEH inhibitors as therapeutic agents.

Thomsen R., Christensen M.H.

In this article we introduce a molecular docking algorithm called MolDock. MolDock is based on a new heuristic search algorithm that combines differential evolution with a cavity prediction algorithm. The docking scoring function of MolDock is an extension of the piecewise linear potential (PLP) including new hydrogen bonding and electrostatic terms. To further improve docking accuracy, a re-ranking scoring function is introduced, which identifies the most promising docking solution from the solutions obtained by the docking algorithm. The docking accuracy of MolDock has been evaluated by docking flexible ligands to 77 protein targets. MolDock was able to identify the correct binding mode of 87% of the complexes. In comparison, the accuracy of Glide and Surflex is 82% and 75%, respectively. FlexX obtained 58% and GOLD 78% on subsets containing 76 and 55 cases, respectively.

RIDA S., ASHOUR F., ELHAWASH S., ELSEMARY M., BADR M., SHALABY M.

In an effort to establish new candidates with improved antineoplastic, anti-HIV-1 and antimicrobial activities we report here the synthesis and in vitro biological evaluation of various series of 2-substituted benzoxazoles: 2-[(Arylhydrazono, arylidene, cycloalkylidene and N-substituted thiocarbamoyl)cyanomethyl]-benzoxazoles(2-4 and 7, respectively); 2-[(4- or 5-oxothiazoliden-2-yliden)benzoxazoles (5 and 6) and 2-(4-amino-3-substituted-2-thioxo-2,3-dihydrothiazol-5-yl)benzoxazoles (8), together with the synthesis of some substituted 3H-pyrido[2,1-b]benzoxazoles (9-11). The absolute configuration of compound 3b was determined by X-ray crystallography. The results of the in vitro anticancer screening revealed that some of the tested compounds exhibited broad spectrum antitumor activity. The most active compounds are 2a, 3b, 8a and 8d, their GI50 MG-MID values: 37.7, 19.1, 20.0 and 15.8 microM; TGI MG-MID values: 75.9, 53.7, 53.7, and 58.9 microM; and LC50 MG-MID values: 97.7, 93.3, 89.1 and 93.3 microM, respectively. The in vitro microbiological data showed that compound 7c was the most active against Staphylococcus aureus (minimal inhibitory concentration (MIC)

Sun L., Chen J., Takaki K., Johnson G., Iben L., Mahle C.D., Ryan E., Xu C.

A novel series of benzoxazole derivatives was synthesized and evaluated as melatoninergic ligands. The binding affinity of these compounds for human MT(1) and MT(2) receptors was determined using 2-[(125)I]-iodomelatonin as the radioligand. The results of the SAR studies in this series led to the identification of compound 28, which exhibited better MT(1) and MT(2) receptor affinities than melatonin itself. This work also established the benzoxazole nucleus as a melatoninergic pharmacophore, which served as an isosteric replacement to the previously established alkoxyaryl core.

Stoykov I.I., Antipin I.S., Burilov V.A., Kurbangalieva A.R., Rostovsky N.V., Pankova A.S., Balova I.A., Remizov Y.O., Pevzner L.M., Petrov M.L., Vasily A.V., Averin A.D., Beletskaya I.P., Nenaydenko V.G., Beloglazkina E.K., et. al.

An overview of the main scientific achievements of Russian universities in the field of organic chemistry for the period 2018–2023 is presented.

Stoikov I.I., Antipin I.S., Burilov V.A., Kurbangalieva A.R., Rostovskii N.V., Pankova A.S., Balova I.A., Remizov Y.O., Pevzner L.M., Petrov M.L., Vasilyev A.V., Averin A.D., Beletskaya I.P., Nenajdenko V.G., Beloglazkina E.K., et. al.

An overview of the main scientific achievements of Russian universities in the field of organic chemistry over the period 2018–2023 is presented.

Danilenko N.V., Lutsuk M.O., Patlasova S.E., Korotkova E.I., Khlebnikov A.I.

New 2-(4-(fluorosulfonyloxy)phenyl)benzoxazole (2) was synthesized through the SuFEx click reaction in a two-chamber reactor. The effect of silylation on the yield of the target compound was investigated. The fluorescent properties of compound 2 were determined using experimental and computational methods.

Rodygin K.S., Lotsman K.A., Erokhin K.S., Korabelnikova V.A., Ananikov V.P.

The syntheses of various chemical compounds require heating. The intrinsic release of heat in exothermic processes is a valuable heat source that is not effectively used in many reactions. In this work, we assessed the released heat during the hydrolysis of an energy-rich compound, calcium carbide, and explored the possibility of its usage. Temperature profiles of carbide hydrolysis were recorded, and it was found that the heat release depended on the cosolvent and water/solvent ratio. Thus, the release of heat can be controlled and adjusted. To monitor the released heat, a special tube-in-tube reactor was assembled using joining part 3D-printed with nylon. The thermal effect of the reaction was estimated using a thermoimaging IR monitor. It was found that the kinetics of heat release are different when using mixtures of water with different solvents, and the maximum achievable temperature depends on the type of solvent and the amount of water and carbide. The possibility of using the heat released during carbide hydrolysis to initiate a chemical reaction was tested using a hydrothiolation reaction—the nucleophilic addition of thiols to acetylene. In a model experiment, the yield of the desired product with the use of heat from carbide hydrolysis was 89%, compared to 30% in this intrinsic heating, which was neglected.