Development of heterocyclic-based frameworks as potential scaffold of 5-HT1A receptor agonist and future perspectives: A review

Abstract

As a subtype of the 5-hydroxytryptamine (5-HT) receptor, 5-HT1A receptors are involved in the pathological process of psychiatric disorders and is an important target for antidepressants. The research groups focus on these area have tried to design novel compounds to alleviate depression by targeting 5-HT1A receptor. The heterocyclic structures is an important scaffold to enhance the antidepressant activity of ligands, including piperazine, piperidine, benzothiazole, and pyrrolidone. The current review highlights the function and significance of nitrogen-based heterocyclics 5-HT1AR represented by piperazine, piperidine, benzothiazole, and pyrrolidone in the development of antidepressant.

Figure 1.

Proposed activation process of 5-HT_1AR by agonist.

Figure 2.

Piperazine-based fananserin derivatives as antidepressants.

Figure 3.

Piperazine-based 1H-imidazo[2,1-f] purine-2,4(3H,8H)-dione derivatives as antidepressants.

Figure 4.

Piperazine-based antidepressants: compounds 6 to 9.

Figure 5.

Potent antidepressant activity after replacing piperazine rings with piperidine derivatives: compounds 10 to 20.

Figure 6.

Structure of potent benzothiazole compounds 21 to 28.

Figure 7.

Binding affinity of pyrrolidine-2,5-dione derivatives for 5-HT_1A receptor.