Abstract As part of our ongoing antileishmanial structure–activity relationship study, a structural simplification of the 3‐nitroimidazo[1,2‐a]pyridine ring to a 5-nitroimidazole moiety was conducted. A series of novel 2,4-disubsituted 5-nitroimidazole derivatives, including the 5-nitroimidazole analog of Hit A and the 4-phenylsulfonylmethyl analog of fexinidazole, were obtained by using the vicarious nucleophilic substitution of hydrogen (VNS) reaction, to substitute position 4, and by using the tetrakis(dimethylamino)ethylene methodology to modulate position 2. The molecular structures of eight novel 5-nitroimidazoles were characterized by 1H NMR, 13C NMR, LC/MS, and HRMS. The in vitro antileishmanial activity of these compounds was evaluated against the promastigote form of Leishmania infantum and their influence on cell viability was assessed on the human hepatocyte HepG2 cell line. The 4-phenylsulfonylmethyl analog of fexinidazole showed the best selectivity index of the series, displaying good activity against both the promastigote form of L. infantum (EC50 = 0.8 µM, SI > 78.1) and the promastigote form of Leishmania donovani (EC50 = 4.6 µM, SI > 13.6), and exhibiting low cytotoxicity on the HepG2 cell line (CC50 > 62.5 µM).

Abstract Triazoles act as important pharmacophores in showing biological activity such as antibacterial, antifungal, antitumour/anticancer, anti-inflammatory activities. Literature review suggests that triazoles have been maximally used in carrying research related activities in reference to biological evaluation as compared to other nitrogen containing five membered heterocycles like tetrazoles, pentazoles, pyrazoles, and imidazoles. The first compound of this class was discovered by Janseen Group in 1960s. The microbes act counteractively towards antibiotics which in turn challenge the efficacy of the drugs and thus create room for the progression of more potent avant-garde drugs. Thus, the synthesis of hybrid molecules has been accelerated from last two decades as the hybrids possess more potency, vigour, and adequacy than its constituting pharmacophores. So, this review represents a condensed report of the research carried out in relation to synthetical procedures and assessment of the antibacterial and antifungal activity of triazoles.

Abstract Imidazoles have a unique position in heterocyclic chemistry as these constitute the basic framework of several bio-molecules. Thus, increasing research is being carried out on the synthesis of imidazoles and their derivatives, mainly because of the application of imidazoles in pharmaceutical and medicinal research. Keeping sustainability in mind, researchers are developing synthetic pathways for the synthesis of imidazoles and their derivatives by employing techniques involving green tools, thus leading to sustainable pathways. In this review, we aim to compile such synthetic methodologies involving green tools for the synthesis of imidazoles. The review will cover the synthetic reactions that involve green tools such as microwave irradiation, ultrasound irradiation, and ball milling. We aim to highlight the scope and relevance of such green tools in today’s synthetic research. Through this review, we wish to contribute towards the synthesis of imidazoles that serve as a useful class of heterocyclic compounds involved in the development of pharmaceutically active molecules. We sincerely hope that this review will serve as a relevant guide for future sustainable research in the synthesis of imidazoles and their derivatives.

Abstract Imidazole and its derivatives possess remarkable versatility, finding applications in medicine, synthetic chemistry, and industry. This review explores the latest advancements observed over the last few years (2018–2022), focusing on diverse multicomponent reactions conducted under different conditions. It highlights the role of catalysts and diverse conditions, optimizing synthetic efficiency. The review offers concise insights into emerging trends, making it a valuable resource for researchers and practitioners seeking greener and more efficient imidazole synthesis.

Abstract Research on gold catalysis has flourished over the last 20 years, and gold catalysts are now acknowledged as the “best choice” for a range of organic transformations. Gold complexes have emerged as promising candidates for this use in recent years because of their high reactivity, which enables them to induce a broad range of transformations under mild conditions. Extensive demonstrations have showcased the extraordinary efficiency of synthesizing complex organic compounds from the basic starting components. In addition to its traditional applications in catalysis, gold catalysis has expanded to include the total synthesis of natural compounds, which is a complex and demanding undertaking. The class of molecules known as carbo- and heterocycles, which is arguably the most important, has a significant impact on the synthesis of agrochemicals and pharmaceuticals among the numerous additional products made possible by the novel procedures pioneered. The main topic of this review is how to use Au salts in homogeneous catalysis to create cyclization processes for small heterocyclic and carbocyclic systems. This study gives an overview of most of the books and articles written after 2013 that discuss making three- and four-membered carbo- and heterocyclic rings with gold as a catalyst. We have made every effort to include all outstanding reports on this subject; nonetheless, we apologize for any omissions.

Abstract Since many of the U.S. Food and Drug Administration (FDA)-approved medications contain oxygen-containing heterocyclic molecules, they have been discovered to be quite important. Moreover, over the past 10 years, the field of reusable nanocatalysts has expanded quickly. Therefore, the development of nanotechnology has led to a wide range of applications for nanocatalysis in the synthesis of heterocyclic molecules. The domains of organic chemistry and pharmaceuticals have recently shown a great deal of interest in nanocatalyzed organic processes. Such nanocatalysts enable non-toxic, simpler, environmentally friendly, and more affordable synthetic processes that give only the most desirable compounds in higher quantities and provide simple catalyst separation. As a result of their efficient methods for separating catalysts and products, nanocatalysts were chosen over other catalysts for the synthesis of heterocyclic compounds. This review emphasized the preparation of nanocatalysts, synthetic approaches, and recycling studies of highly excited catalytic systems employed for the synthesis of oxygen-containing heterocyclic compounds.

Abstract A series of novel 5-aryldiazenyl-1,2,4-triazol-3-ones are synthesized at room temperature in short reaction time, and excellent yields via four-component reaction between 4-aryldiazenyl-salicylaldehydes, ammonium acetate, arylhydrazine, and carbon dioxide using bis(thioglycolic acid)-vanillin (2,2′-(((4-hydroxy-3-methoxyphenyl)methylene)bis(sulfanediyl))diacetic acid)‐functionalized silica-coated Fe3O4 magnetic nanocomposite (Fe3O4@SP-vanillin-TGA MNCs). The present protocol offers several advantages such as gentle reaction conditions, excellent performance, simple fabrication, separation methods, and reduction of detrimental environmental consequences. The catalyst could be easily recovered and reused for six runs with nearly steady activity. The structures of the synthesized 5-aryldiazenyl-1,2,4-triazol-3-ones have been confirmed with the aid of using 1H, 13C NMR, and fourier transform infrared spectral data and elemental analyses.

Abstract Quinoxalines are a family of nitrogen-based heterocyclic compounds that have garnered much interest because of their wide range of applications. 2,3-Dichloroquinoxaline is an aromatic molecule that frequently serves as a synthetic intermediate in materials science, pharmaceuticals, and organic chemistry. 1,3-Dithiolo[4,5-b]quinoxaline derivatives 8a–c and thiazolo[4,5-b]quinoxaline derivatives 11a,b were synthesized by the reaction of 2,3-dichloro-6-sulfonyl quinoxaline derivative 5 with 1,3-binucleophiles. Moreover, 1,3-dithiolo[4,5-b]quinoxalin2-ylidene derivatives 8a–c were obtained by treating 2,3-dichloro-6-sulfonyl quinoxaline derivative 5 with potassium salts of hydrazonodithioates 7a–c at room temperature. Additionally, 2,3-dichloroquinoxaline derivative 5 was reacted with thioureas 9a,b in 1,4-dioxane to yield 6-(pyrrolidin-1-yl sulfonyl)thiazolo[4,5-b]quinoxalin-2(3H)-imines 11a,b rather than thiazolo[5,4-b]quinoxaline 10. Elemental analysis, infrared spectroscopy, 1H NMR, 13C NMR, and mass spectroscopy were used to confirm the structures of the newly synthesized compounds. Finally, we used artificial intelligence to perform biological evaluation via predicting the possible molecular targets and antimicrobial activity of the designed derivative. The results showed good bacterial activity, weak fungal potency, and potential biological targets.

Abstract The present work deals with the synthesis of 2-cyano-N′-(3-(2-(2-cyanoacetyl) hydrazinyl) cyclohex-2-en-1-ylidene) acetohydrazide 3 that used as a key precursor in the manufacture of new heterocyclic derivatives, such as pyrazole, pyrane, pyridine, and pyrole incorporating cyclohexene moiety via its reaction with a variety of nucleophilic and electrophilic reagents. The newly synthesized compounds were characterized by their elemental analyses (IR, 1H-NMR, 13C-NMR, and Mass spectra) and assessed for their anti-microbial activity.

Abstract N-Substituted-2-propanamide analogues of 1,3,4-oxadiazole have been synthesized using a multi-step synthetic protocol to explore new therapeutic anti-enzymatic agents. Herein, we have merged sulfonyl, piperidine, oxadiazole and amide into a single unit to synthesize a library of unique compounds, 8a–n. The molecular structures of all synthesized compounds were verified by 13C-NMR, 1H-NMR, HRMS and IR spectroscopy. Furthermore, the compounds were screened for their inhibition potential against acetylcholinesterase (AChE), urease and lipoxygenase (LOX) enzymes. A considerable inhibition potential was observed for three compounds against LOX with quercetin as a reference standard, two compounds against urease with thiourea as a reference standard and two compounds against AChE with eserine as a reference standard. Through molecular docking investigations, we were able to correlate the overall impact and inhibition criteria by the structure–activity relationship via the interactions between synthesized compounds and active sites of enzymes. Pharmacodynamics, pharmacokinetics and in vivo studies may be investigated further for the most active compounds to substantiate them as potential anti-enzymatic medications.