The therapeutic potential of scaffold containing substituted amine derivatives in the drug design of antidepressant compounds.

Depression is a complex, progressive mental disorder and a major risk factor for suicide. The available therapeutics are highly unmet the clinical demands in terms of safety and efficacy. The presence of the substituted amine structural fragment in numerous pharmaceutical compounds has shown a wide range of biological activities, including those of central nervous system (CNS) depressant drugs. Results of different studies showed the presence of substituted amine in many bioactive natural compounds exhibiting potent antidepressant activity. The substituted amine motif-containing derivatives showed the antidepressant action through varied mechanisms that include selective serotonin/norepinephrine reuptake inhibitors, blocking of N-methyl-d-aspartate (NMDA) receptors, 5-Hydroxytryptamine receptors (5-HT7) antagonist, monoamine oxidase A (MAO-A) inhibition, etc. Cumulative research from the last few decades showed that these derivatives, having a substituted amine motif, possess antidepressant potential. These reported compounds showed progress in tackling side effects and improving the antidepressant potential of the newly developed compounds. Therefore, it can be postulated that substituted amine might possess a significant role in the design of therapeutic modalities that can act as promising therapeutics in the central nervous system (CNS) disorders, such as depression. This review presents the synthetic derivatives containing substituted amine in various scaffolds such as indole, piperidine, piperazines, quinazolines, aryl-sulfonamides, and cinnamamide. Further, we have included the results of the heatmap study for predicting the comparative potency, matrix-based visualization, and metabolic stability from the multiple published studies to support the design of substituted amine-containing compounds. The analysis of the structure-activity relationship (SAR) of these substituted amine-containing derivatives discussed in the article will further support the progression of safer antidepressants.