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Review
. 2023 Jun 13;16(6):873.
doi: 10.3390/ph16060873.

Recent Advances in the Green Synthesis of Active N-Heterocycles and Their Biological Activities

Suman Majee  1   2 , Shilpa  2 , Mansi Sarav  2 , Bimal Krishna Banik  3 , Devalina Ray  1   2
Affiliations
Review

Recent Advances in the Green Synthesis of Active N-Heterocycles and Their Biological Activities

Suman Majee et al. Pharmaceuticals (Basel). .

Abstract

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.

Keywords: N-heterocyclic compounds; bioactivity; drug design and development; green synthesis; pharmaceutical activity.

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Conflict of interest statement

There is no conflict of interest or known competing financial interest that could have appeared to influence the work reported in this paper.

Figures

Figure 1
Figure 1
Natural-product-derived N-heterocyclic drugs and bioactive compounds.
Figure 2
Figure 2
Synthetic N-heterocyclic drugs and bioactive compounds approved by FDA recently.
Scheme 1
Scheme 1
Synthesis of pyrazole derivatives via MCR under microwave heating.
Scheme 1
Scheme 1
Synthesis of pyrazole derivatives via MCR under microwave heating.
Figure 3
Figure 3
Bioactivity of pyrazole derivatives in cell lines A-549 and HepG2.
Scheme 2
Scheme 2
Synthesis of pyrazole derivatives via MCR under microwave heating and their biological evaluation.
Scheme 3
Scheme 3
Synthesis and cytotoxic effect of benzimidazole derivatives against MCF-7 cells.
Scheme 4
Scheme 4
Microwave-irradiated synthesis of sugar–benzimidazole conjugates for antibacterial evaluation.
Scheme 5
Scheme 5
Microwave-assisted synthesis of tetracyclic benzimidazole derivatives.
Figure 4
Figure 4
Bioevaluation of benzimidazole derivatives in various cell lines.
Scheme 6
Scheme 6
Microwave-assisted synthesis of benzimidazole derivatives and their antiviral activity.
Scheme 7
Scheme 7
Microwave-assisted synthesis of 1,2,3,4-tetrhydropyrimidines derivatives.
Scheme 8
Scheme 8
Synthesis of pyridopyrimidine-2-thiones in ionic liquid under microwave conditions for AChE and BChE inhibition.
Scheme 9
Scheme 9
Microwave-assisted synthesis of pyridopyrimidine derivatives.
Scheme 10
Scheme 10
Microwave-irradiated synthesis of coumarin–pyrimidine conjugates.
Scheme 11
Scheme 11
Microwave-assisted synthesis of pyrimidine derivatives.
Scheme 12
Scheme 12
Microwave-irradiated synthesis of quinoline derivatives.
Scheme 13
Scheme 13
Synthesis of pyrazolo[4,3′:5,6]pyrido[2,3-d]pyrimidine derivatives.
Scheme 14
Scheme 14
Microwave-assisted click reaction of bisazides with alkynes.
Figure 5
Figure 5
Antimicrobial activities of 1,2,3-triazole-benzodiazepine conjugates.
Scheme 15
Scheme 15
Synthesis of mono and bis-1,2,3-triazole-conjugated benzodiazepines.
Scheme 16
Scheme 16
Microwave-assisted synthesis of tetrazole–benzodiazepines conjugates and their antifungal activity.
Scheme 17
Scheme 17
Microwave-irradiated synthesis of 1,5-benzodiazepine derivatives and their antibacterial evaluation.
Scheme 18
Scheme 18
Synthesis of pentacyclic benzodiazepines under microwave irradiation.
Scheme 19
Scheme 19
Synthesis of tetrahydropyrimidine-4-yl pyrimidines and their inhibitory activities of cholinesterase enzymes.
Scheme 20
Scheme 20
Solvent-free synthesis of substituted 3,4-dimethoxy-phenyl ethylamines.
Scheme 21
Scheme 21
Synthesis of isoindolo[2,1-a]quinazolines as potent inhibitors of TNF-α.
Scheme 22
Scheme 22
Synthesis of imidazole scaffolds with reduced graphene oxide/NiO nanocomposites.
Scheme 23
Scheme 23
Synthesis of tetrazole derivatives and their bioevaluation against hAChE and hBuChE.
Scheme 24
Scheme 24
Ultrasound mediated-synthesis of N-substituted pyrrole derivatives.
Scheme 25
Scheme 25
Ultrasound-promoted synthesis of novel pyrimidine derivatives.
Scheme 26
Scheme 26
Synthesis of substituted 1,5-benzodiazepines using biocatalyst and their IC50 values in different cancer cell lines.
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