Table 32.

Comprehensive SAR of the reported N-heterocyclic scaffolds.

N-Heterocyclic Scaffold	SARs	Key Highlights	References
Triazole		•Inhibits the MTase inhibitor. •The presence of bulkier substituents on the silyl group and triazole moiety enhances inhibition activity.	[91]
		•Inhibits the ns2B-nsP3 protease. •The presence of halogens as substituents affects inhibition.	[92]
Pyrazole		•Inhibits DENV. •EDG decreases inhibitory activity. •EWG increases inhibitory activity.	[101]
		•Inhibits DENV2. •The existence of –SO2NH2 at the R2-position exhibited the highest inhibition.	[102]
		•Inhibits DENV2. •The existence of fluorine exhibits maximum inhibition.	[103]
Imidazole		•Inhibits the RdRp DENV polymerase. •The existence of cyano substituent on the imidazole ring exerts greater inhibitory activity as compared to the amide substituent. •The rate of inhibition got enhanced when the substituent on the ribofuranosyl is oxygen followed by sulfur and selenium.	[115]
Pyridine & Fused Pyridine		•Inhibits the RdRp DENV polymerase. •Involved in chelation of the divalent metal ions present on the active site of DENV RdRp polymerase.	[120]
		•Shows greater affinity towards GAK. •Electron-donating substituents on the phenyl ring of the fused isothiazole scaffold enhanced the inhibition activity. •Substituents on the phenyl ring and the isothiazole ring are crucial for showing anti-dengue activity.	[124]
		•Shows inhibition towards GAK. •The existence of substituted morpholine group at 3-position and aryl substituent at 6-position is responsible for exhibiting GAK inhibition.	[127]
Pyrazine		•Inhibits DENV. •Pyrazine moiety contributes significantly to the inhibition activity. •Electron-donating, as well as electron-withdrawing substituents, play a critical role in the rate of inhibition.	[101]
Pyrimidine		•The existence of electron-donating and electron-withdrawing groups on the substituted pyrimidine scaffold affects DENV. •The existence of the –OCF3 group at a different position on the phenyl ring affects the inhibition activity.	[139]
		•Suppresses activity against all the DENV serotypes. •The presence of the Piperidine ring and the length of the side-chain on the pyrimidine scaffolds enhance the dengue inhibition. •Heterocyclic scaffolds as side-groups posed a decrease in the inhibition activity.	[141]
Indole		•Inhibits the larvicidal activity of Aedes aegypti mosquitoes. •The existence of chlorine and bromine as the side groups of the indole-ring hinders the growth of larvae. •The existence of the –COOH group increases the growth of larvae.	[151]
		•Inhibits DENV2. •The presence of the methoxy-group at the meta-position is responsible for the maximum and selective inhibition. •Monocyclic or bicyclic aryl groups are the preferred choice for displaying inhibition activity.	[152]
		•Inhibits DENV2. •The p-nitro hydrazine substituents significantly enhance the anti-dengue activity. •The presence of silylating protecting groups suppresses dengue replication.	[153]
		•Inhibits DENV-2 protease. •The presence of the furyl-group enhances the anti-dengue activity. •The existence of cyclohexyl or piperidine substituents at the R′-position displayed improved inhibition.	[154]
Quinoline		•The electronic substituents on the quinoline scaffold and substituted aniline can significantly affect the inhibition activity. •Bromine as the substituent as the R-group on the quinoline scaffold showed an increase in the inhibition. •The electron-donating groups and heterocyclic scaffolds as the R′-position displayed improved inhibition.	[162]
Quinazoline		•Inhibits NS2B-protease. •The electron-releasing groups at the p-position possess better inhibition ability as compared to the m-position. •The side-groups at 2- and 4-position of the aminoquinazoline derivatives are vital for showing inhibition activity.	[169]
		•The electron-withdrawing groups on the R1-position enhance the inhibition activity. •Halogen substituents except for the fluoro-group cause an increase in the inhibition rate. •The electron-withdrawing substituents decrease the inhibition activity present in the R2-position.	[170]
		•R4 and R5 positions are significant for greater inhibition. •The presence of acetylene further strengthens the rate of inhibition.	[171]