Nasser Amri

Mechanochemical activation offers a powerful means of expanding the reactivity of hypervalent iodine reagents while advancing solvent-free synthetic methodologies. This review surveys the evolution of iodine(III) and iodine(V) chemistry in the solid state, from foundational solvent-free oxidations to mechanochemical approaches that enable efficient heterocycle construction, C–H functionalization, cascade dioxygenation, fluoroiodane-mediated fluorocyclization, and redox-initiated polymerization. Mechanical energy alters aggregation, enhances reagent–substrate contact, and promotes transformation pathways not readily accessible in solution. These developments showcase the distinctive advantages of mechanochemical hypervalent iodine chemistry and its growing impact on sustainable synthetic methodology development.

Isoquinolinoquinazolines and their derivatives represent a significant class of nitrogenbased heterocycles that have attracted substantial interest from researchers worldwide. This review builds on our previous work by summarizing recent advancements in this class of compounds, specifically focusing on novel isoquinolino[2,3-a] quinazolines published between 1991 and 2026. It highlights their pharmacological and biological activities, as well as the mechanisms of action underlying these effects. Advances in synthetic modification strategies have significantly enhanced the synthesis of isoquinolino[2,3-a] quinazolines, enabling their successful production. Over 128 molecules demonstrating a wide range of biological activities, including antitumor, antimicrobial, analgesic, antioxidant, and cardioprotective effects, have been synthesized and discussed. The total synthesis of Isoquinolino[2,3-a] quinazolines was discussed across 7 classes, each involving distinct compounds, reagents, and methods. This review provides new insights and opportunities for drug discovery involving Isoquinolino[2,3-a] quinazolines.

Heterocyclic compounds, such as pyrazole, triazole, and imidazopyridine and their derivatives, are highly significant in biological applications due to their antimicrobial, antiviral, anticancer, antioxidant, antibiotic, antitubercular, analgesic, and anti‐inflammatory activities. We prepared a series of novel products, including 2‐(sub‐benzylidene)‐indene‐1,3‐diones (2–5) , 2‐(substituted‐ylmethylene)‐1( H )‐indene‐1,3‐diones (6–8) , and more complex derivatives such as 2‐((2‐( p ‐chloro‐phenyl)imidazo [1,2‐ a ]pyridine)methylene)‐indene‐1,3‐dione (9) , as well as various pyrazolyl and benzofuranyl and 1,2,3‐triazolyl derivatives (10–12) . These compounds were characterized using spectroscopic methods, including IR, NMR, and MS. Their antimicrobial activities were evaluated in vitro, with comparisons made against standard drugs cefotaxime sodium and nystatin. This research highlights the medicinal potential of these heterocyclic structures and the diversity of imidazo[1,2‐ a ] pyridine, triazole, and pyrazole derivatives linked to indane‐1,3‐dione. The findings may contribute to future drug discovery and therapeutic development. The compounds' antimicrobial activity was tested in vitro. The results indicated that products ( 9–12) had the highest antimicrobial activity. Molecular docking analyses and studies exploring the relationship between these compounds' structures and their activity further supported this finding. Consequently, compounds (9–12) are regarded as promising multi‐target agents that could potentially be developed into standard drugs in the future.

Isoquinolino[1,2-b] quinazolines are heterocyclic compounds that have gained significant attention in recent years due to their important applications in the pharmaceutical, agricultural, and chemical industries. They are used as antiviral, anticancer, and antimicrobial agents. This review examines various synthetic strategies for producing isoquinolino[1,2-b]quinazolines, focusing on ruthenium(II) and rhodium catalysts. It includes derivatives that incorporate quinazoline and isoquinoline building blocks. Additionally, the review discusses the reactivity of isoquinolino[1,2-b] quinazolines in ring-opening and ring-expansion reactions. It also highlights the total syntheses of selected isoquinolino[1,2-b]quinazoline derivatives, employing diverse methodologies, and explains their biological activities. Most of the literature reviewed consists of reports published since 1996, although some earlier significant contributions are also referenced.

Indole and quinoxaline are important alkaloids that make up a significant subset of natural products. Many of these alkaloids exhibit biological activity due to their nitrogen-containing structures, which demonstrate notable antiviral, antitumor, antimicrobial, antimalarial, herbicidal, and anti-plasmodial properties. This review focuses on the preparation of heterocycles and bioactive compounds related to indolo[2,3-b] quinoxaline derivatives. It also discusses multiple synthesis methods and their associated biological activities. We cover a wide range of compounds and reagents used in the synthesis of indolo[2,3-b] quinoxaline and its derivatives, with a particular emphasis on their yields. Over 140 compounds are discussed in this review, supported by more than 85 references. Additionally, we explore various chemical reactions, including condensation, cyclization, Suzuki-Miyaura cross-coupling reaction, substitution, alkylation, multi-component reactions, hydrolysis, oxidation, reduction, Mannich base formation, and the Vilsmeier–Haack reaction, and others. Given the significant biological activities of indolo[2,3-b] quinoxaline derivatives, which are found in certain medications, such as the aza-analogues of the cytotoxic agents ellipticine and cryptoleptine, these synthetic methods enable the efficient production of these compounds. This advancement will foster further research into their potential applications in the pharmaceutical industry.

Background: Recently, compounds such as pyrimidine, pyridazine, 1,2,4-triazepine, 1,3,4,6-oxatriazepine, pyridazino[1,2-a]pyrimidine, and pyridazino[1,2-c] pyrimidine, as well as their derivatives, have attracted attention due to their diverse biological activities. Objective: This study focuses on the synthesis of new heterocyclic compounds that feature a seven-membered ring, including pyridazinopyrimido[2,1-c] [1,2,4]triazepine-tetraones (4), pyridazinopyrimidotriazepine-triones (5–8), aminopyri-dazinopyrimido[2,1-c][1,2,4]triazepine-tetraone (9), and 6-amino-8-imino-pyridazino pyrimido[2,1-c] [1,2,4]triazepine-trione (10). These new compounds were synthesized starting from 1-(4-oxo-1,4-dihydropyrimidine)-1,2-dihydropyridazine-3,6-dione (3) and were then evaluated for their antimicrobial activity. Methods: A new series of pyridazino[1,2-a]pyrimido[2,1-c][1,2,4]triazepines and 1,3,4,6-oxatriazepines were synthesized using modern techniques and advanced technology, achieving yields between 72% and 90%. Results: All new compounds were confirmed through IR, ¹H NMR, ¹³C NMR, and mass spectroscopy (MS) and tested for in vitro antimicrobial activity. Compounds (8-10) exhibited excellent antimicrobial activity. Computational analysis provided a comprehensive evaluation of the broad-spectrum inhibitory potential of four lead compounds (6, 8, 9, and 10) against key microbial and fungal targets. These compounds demonstrated consistently superior binding affinities compared to control drugs cefotaxime and nystatin across a range of enzymes essential for pathogen viability and virulence. Conclusions: The structure–activity relationship (SAR) study established a correlation between the tested compounds and their antimicrobial activity. Molecular docking analysis indicated that the in silico results strongly suggest that compounds (6, 8, 9, and 10) are promising multi-target agents capable of disrupting essential bacterial processes and critical fungal pathways, making them excellent candidates for the development of novel antimicrobial therapeutics. These consistent findings support the conclusion that both practical and theoretical studies of the new compounds align with their antimicrobial effectiveness.

Isoquinoline, quinoline, and pyrimidine are heterocyclic compounds with great potential for developing new drugs. When combined in isoquinoline-pyrimidine-inspired hybrids, they demonstrate numerous beneficial biological properties. Recently, many studies have focused on the synthesis and medicinal chemistry applications of pyrimido[4,5-c]isoquinoline ring systems (PyisoQs4,5- c). This review offers a comprehensive overview of the synthesis of Py-isoQs4,5-c using pyrimidine, 6-amino-1,3-dimethyl-pyrimidine-dione, 6-amino-2-thioxopyrimidinone, 5-chlorodimethylpyrimidin- 4-amine, ethyl benzoate, cyclohexane-dione, cyclopentadiene, benzoquinone, naphthalene-dione, dihydronaphthalenone, isophthalonitrile, dihydroxybenzaldehyde, cycloheptanone, furan-methanol, dimethyl but-2-ynedioate, and their derivatives. These compounds are synthesized through various chemical reactions, including condensation, cyclocondensation, alkylation, substitution, one-pot three-component, cross-coupling, Vilsmeier, Suzuki–Miyaura, Diels- Alder reactions, and Pictet–Spengler reactions. These synthetic approaches allow for the efficient construction of Py-isoQs4,5-c, facilitating further exploration and investigation of their potential medicinal applications.

The oxadiazepine moiety and its derivatives are crucial in developing new drugs. Combined with various compounds such as phthalazine, imidazole, pyrazole, indole, benzofuran, and thiazolopyrimidine, they exhibit beneficial biological properties. Recent studies have made significant progress in synthesizing oxadiazepine derivatives, enhancing our understanding of their potential medicinal applications. This review offers a comprehensive overview of these advancements, detailing the synthesis of various oxadiazepine derivatives and the chemical reactions involved. Here are some examples of the compounds discussed in this review: 3,6-di-nitro-1,3,6- oxadiazepane; 1,3,6-oxadiazepinodiphthalazine; 6-(1,3,6-oxadiazepane)-glycyl-L-alanine; benzoimidazo- 1,3,6-oxadiazepine; azepino[1,2-c][1,3,6]oxadiazepine; dipyrazolo-1,3,6-oxadiazepine; sub-1,3,6-oxadiazepine-diindole; benzooxazino[3,4-b]benzo[5,6][1,4] oxazino[4,3-f][1,3,6]- oxadiazepine-6,8-diol and 2-(2-chloroethyl)-11-methyl-1,3,6-oxadiazepino[3,4-a]indole derivatives. These compounds are created through chemical reactions such as alkylation, condensation, cyclization, coupling, substitution, oxidation, reduction, multi-component reactions, intramolecular Mannich bases, and hydrolysis. Considering the significant biological activity of oxadiazepine derivatives, which are found in certain drugs such as staurosporine, these synthetic methods facilitate the efficient production of these compounds, thus encouraging further research into their potential pharmaceutical applications.

Quinoline, isoxazole, and pyridothiazolopyrimidinone derivatives are novel compounds with significant biological activity, exhibiting anticancer properties and holding promising therapeutic applications. This investigation synthesized new heterocyclic compounds in high yields from quinoline-2-thioxo-pyridopyrimidinone and assessed their anticancer activities. Additionally, it conducted molecular docking, ADMET analysis, and molecular dynamics simulations. A new series of quinoline-pyridothiazolopyrimidine derivatives has been synthesized using advanced techniques. The structures of the new compounds were confirmed using IR, NMR, MS and elemental analysis. All compounds were tested in vitro for their anticancer activity. Isoxazole and thiazolopyridopyrimidinones displayed the highest activity against several cancer cell lines. Docking simulations revealed that compounds 5d, 5e, 11a, and 11b exhibited favorable binding energies and effectively interacted with the active sites of the EGFR, CDK2, ERα, and VEGFR receptors. The ADMET analysis of these compounds demonstrated compliance with Pfizer's rules. Molecular dynamics simulations confirmed the stability of complexes formed by compounds 5d, 11a, and 11b with CDK2, ERα, VEGFR, and EGFR. The root mean square deviation (RMSD) values were recorded, while the root mean square fluctuation (RMSF) values ranged from 0.10 to 0.6 nm. The solvent-accessible surface area (SASA) values were measured to be between 135-145 nm², 125-130 nm², 155-165 nm², and 160-175 nm². The cytotoxicity (IC₅₀) and selectivity index are presented in Tables. Molecular docking analyses showed that compounds 5d, 5e, 11a, and 11b demonstrated significant binding energies. These consistent results support the notion that both practical and theoretical studies align regarding the anticancer properties of these new compounds. Furthermore, these findings emphasize the potential of these compounds in ongoing drug development efforts.