Current Organic Chemistry - Volume 27, Issue 1, 2023

The EGFR (Epidermal Growth Factor Receptor) regulates cell proliferation, survival, and differentiation. The EGFR is a cell surface receptor that belongs to the ErbB tyrosine kinase family. One of the most important targets for cancer therapy is EGFR inhibition. Because EGFR over-activation is seen in a wide range of malignancies, targeting EGFR and its downstream signaling cascades is a sensible and beneficial strategy in cancer therapy. This review highlighted the most potent EGFR inhibitors with SAR studies and their synthetic chemical pathways discovered between 2010-2020, employed for treating Liver, Breast, Lung, Pancreatic, and Colorectal cancers. We also include the clinical trials and the registered patents in our review.

Arylsilanes are the basic raw material for the synthesis of advanced silicone new materials such as phenylsilicone resin, phenylsilicone oil and phenyl silicone rubber, etc. The silicone polymers containing aryl groups were applied widely in the fields including electronics, and aerospace. In the past decades, arylsilanes have been widely used in organic synthesis, such as Hiyama coupling, C-N bond formation, synthesis of biaryl, polyketone polymer, and so on. Therefore, synthetic research on arylsilanes has also received wide attention. In this paper, the research progress of the synthesis and applications of arylsilanes in the past decades has been reviewed.

1,3-Benzazoles (BZs) are interesting compounds in medicinal chemistry. For instance, compounds with the BZ nucleus exhibit diverse biological activities and some of them are broadly utilized in clinical applications. In this sense, medicinal chemists aim at the development of new procedures to synthesize these kinds of molecules. The 2-aminobenzimidazole 2ABI derivatives, such as Enviradine (antiviral), Astemizole (antihistaminic), and Albendazole (antimicrobial), which contain the intra-cyclic guanidine nucleus, are used in medicinal chemistry. The guanidine group, considered a super base, when bonded to a benzazole ring, results in the 2-guanidinobenzazoles (2GBZs), modifying the biological activity of these heterocycles. The structure of 2GBZs is of significance as the 10-π electron system of the aromatic benzazole ring is conjugated with the exocyclic guanidine group to acquire a planar delocalized structure. This class of molecules has at least four nitrogen atoms with free lone pairs and four labile hydrogen atoms, resulting in these compounds having amphoteric character. On the other hand, synthetic chemists have used 2GBZs as a building block to produce derivatives as medicinally important molecules. On these bases, in this work, we prepared a bibliographic review of the methodologies reported in the literature used in the synthesis of 2GBZ derivatives of pharmacological interest. We focused the investigation on 2-guanidinebenzoxazol (2GBO), 2-guanidinebenzothiazol (2GBT) and 2-guanidinebenzimidazole (2GBI) as building blocks. We found that compounds derivatives were N-substituted-2GBZs, 2-(pyrimidyl)-ABZs and 1,3,5-triazino[1,2-a]-BZs, which are described chronologically. This work will help searchers related to bioorganic chemistry, inorganic chemistry, medicinal chemistry and pharmaceutical industry in the recent methodologies to synthetize 2-guanidinobenzazole derivatives to be proposed as materials in the different areas. This topic will provide information on the utility for medicinal chemists dedicated to the design and synthesis of this class of compounds to be tested with respect to their biological activities and be proposed as new pharmacophores.

C-C bond formation in a regiospecific and atom economic manner has been a challenge, which was tried to be resolved through directing group and organometals-based C-H activation strategy. The C-H activation and its advantages are well explored in the field of organic chemistry, with the relevant mechanistic approach of the regioselective C-H activation of the aryl group. Organometals like Ru, Pd, Pt, Ni, etc. have been best discovered for the innate C-H activation where the pre-activation of the inert C-H bond was not found necessary. In the progress of these reactions through organometals, the various forms of ruthenium have been tried with the different directing groups as well as the substrate. Here in we are focusing mainly on cationic ruthenium, and its use in the C-H activation. The cationic ruthenium shows unique characteristics like reactivity with an inert substrate, which is been highlighted here in the examples. The formation and its, mechanistic role is also exemplified with the diagrammed representation of C-H activation and its catalytic cycle. The application of the cationic ruthenium will give complete knowledge about cationic ruthenium and its application in C-H activation.

Aims: In this study, the synthesis and biological activity of new 1,3,4-oxadiazole derivatives will be discussed. Background: Microbial contagion via different bacterial strains discomposes the healthcare system globally. In 2019 E. coli, S. aureus, K. pneumoniae, and S. pneumoniae were reported as the most bacteremia deaths causes. Over time, bacteria develop different ways to overcome antibiotic activity, causing multidrug resistant bacteria (MDR). The MDR is considered one of the biggest concerns to scientists worldwide due to its direct effect on patients' lives. As a result, developing new drugs has become imperative for scientists to protect human life. Objective: Developing new water soluble antibacterial drugs from cheap and commercially available materials. Methods: Microdilution Assay Antimicrobial potential was performed based on the reported experimental procedure with slight modifications. Briefly, chemical preparations were serially diluted (2-fold) ten times with Muller Hinton broth. Well number eleven was considered a negative control of bacterial growth, while well number twelve contained nutrient broth only and was used as a positive control for bacterial growth. The achieved ten concentrations of the chemical solutions were from 10 mg/mL to 9 μg/mL. A serial two-fold dilution of DMSO with Muller Hinton broth was prepared to ensure that the antimicrobial potential was not from DMSO. Moreover, the blank or the background was a two-fold dilution for each chemical with broth. The final bacterial concentration in each well (except positive control) was adjusted to 0.75 × 10⁶ CFU/ml. After the inoculation of bacteria, the plates were covered and incubated overnight at 37°C for 24 hours. The plates were then scanned with an enzyme-linked immunosorbent assay (ELISA) reader at 600 Nano moles to examine the bacterial density. The lowest concentration of the chemical that did not allow any visible microbial growth in the test broth was considered the minimal inhibitory concentration (MIC), which was then further confirmed by culturing each (MIC) well on Muller Henton agar and incubating overnight at 37°C for twenty-four hours. The molecular geometries of compounds 4a, 4e, 4j, and 4p were optimized at the B3LYP/6-311+G(d,p) level of theory using DFT calculations. Results: The antimicrobial examination results show that compound 4j has an interesting activity against E. faecium with MIC value of 9 μg/mL. However, it was found to have low activity against E.coli and K. pneumoniae with an MIC value of 625 μg/mL. On the other hand, compound 4e showed very good activity against E.coli with an MIC value of 78 μg/mL and good activity against K. pneumoniae with an MIC value of 312 μg/mL. The structural properties were further investigated by density functional theory (DFT) calculations. The most biologically active compounds 4e and 4j were optimized in the gas phase using B3LYP method and 6-31+G(d,p) as a bases set. The resulting ground-state structures take a V shape as the two conjugated system are connected by methylene group. The molecular electrostatic potential map (MEP) of 4e and 4j was calculated and the results indicate that, the most intense blue region with the largest positive potential is distributed over the pyridinium ring, which indicates its binding with the chloride ion.