N-heterocyclic scaffolds represent a privileged architecture in the process of drug design and development. It has widespread occurrence in synthetic and natural products, either those that are established or progressing as potent drug candidates. Additionally, numerous novel N-heterocyclic analogues with remarkable physiological significance and extended pharmaceutical applications are escalating progressively. Hence, the classical synthetic protocols need to be improvised according to modern requirements for efficient and eco-friendly approaches. Numerous methodologies and technologies emerged to address the green and sustainable production of various pharmaceutically and medicinally important N-heterocyclic compounds in last few years. In this context, the current review unveils greener alternatives for direct access to categorically differentiated N-heterocyclic derivatives and its application in the establishment of biologically active potent molecules for drug design. The green and sustainable methods accentuated in this review includes microwave-assisted reactions, solvent-free approaches, heterogeneous catalysis, ultrasound reactions, and biocatalysis.

An ecofriendly, atom-economical, iodine-catalyzed, regioselective C-5 chalcogenation of 8-aminoquinolines and its application in the late stage derivatization of primaquine analogues under mild conditions has been established.

The synthesis of heterocyclic compounds has drawn considerable attention in the scientific community due to their existence in the majority of medicinal & pharmaceutically important compounds as well as natural products. Among them, the remarkable existence of tetrazoles has been realized in several commercially available drugs. In this regard, various synthetic protocols to access tetrazoles have been developed to address the efficiency and environmental impacts in terms of minimization of the steps, elevating yields, and conducting environmentally benign and sustainable chemistry. The management and detrimental environmental impact of waste has been recognised as a consistent concern, along with the costs associated with its disposal. Among various approaches to minimise unwanted materials from a process, one of the best alternatives is to perform a reaction in the absence of excess chemical reagents and catalysts. Other options include the reactions affected by the application of heat, light, sound, or electrolysis. The multicomponent reactions (MCR) display a unique approach establishing a step forward toward clean, step and atom-economical chemical synthesis. Most of them utilize the required substrates, eliminating the stoichiometric use of reagents, reducing the possibility of forming unwanted side products. The present review displays the concepts of MCR in the synthesis and functionalization of tetrazole, which contributes to green and sustainable chemistry.

COVID-19 has currently emerged as the major global pandemic affecting the lives of people across the globe. It broke out from Wuhan Province of China, first reported to WHO on 31st December 2019 as “Pneumonia of unknown cause”. Over time more people were infected with this virus, and the only tactic to ensure safety was to take precautionary measures due to the lack of any effective treatment or vaccines. As a result of unavailability of desired efficacy for previously repurposed drugs, exploring novel scaffolds against the virus has become the need of the hour. In the present study, 23 new annomontine analogues were designed representing β-Carboline based scaffolds. A hypothesis on its role as an effective ligand was laid for target-specific binding in SARS-CoV-2. These molecules were used for molecular docking analysis against the multiple possible drug targets using the Maestro Interface. To ensure the drug safety of these molecules ADME/Tox analysis was also performed. The molecular docking analysis of the 23 novel molecules indicated the efficiency of these derivates against COVID-19. The efficiency of molecules was computed by the summation of the docking score against each target defined as LigE Score and compared against Hydroxycholoquine as a standard. Based on the docking score, the majority of the annomontine derivatives were found to have increased binding affinity with targets as compared to hydroxycholoquine. Due to the lack of efficiency, effectiveness, and failure of already repurposed drugs against the COVID-19, the exploration of the novel scaffold that can act as effective treatment is much needed. The current study hence emphasizes the potential of Annomontine based - β- Carboline derivatives as a potential drug candidate against COVID-19.