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A series of 2-[4-(aryl substituted) piperazin-1-yl]-N-benzylacetamides were synthesized and the target compounds (3a–j) were evaluated for atypical antipsychotic activity by studying apomorphine induced climbing behavior, 5-HTP induced head twitches behavior and catalepsy in mice. The physicochemical similarity of the target compounds with respect to standard drugs clozapine, ketanserin and risperidone was assessed by calculating from a set of physicochemical properties using software programs. The test compounds (3a–j) demonstrated good similarity values with respect to the standard drugs. Among them, compound 3b has emerged as an important lead compound showing potential atypical antipsychotic-like profile.

Serotonin (5-hydroxytryptamine) is a small molecule that acts both in the central and peripheral nervous system as a neurotransmitter and a hormone, respectively. Serotonin is synthesized via a multi-stage pathway beginning with l-tryptophan, which is converted by an enzyme called tryptophan hydroxylase into L-5-Hydroxytryptophan. It is well-known for its significance in the control of mood, anxiety, depression, and insomnia as well as in normal human functions such as sleep, sexual activity, and appetite. Thus, for medical chemists and pharmaceutical firms, serotonin is one of the most desirable targets. Among the seven different classes of serotonin receptors, the 5-HT 1A was one of the first discovered serotonin receptors, and the 5-HT 7 was the last addition to the serotonin receptor family. Both the classes were thoroughly examined. 5-HT 1A neurotransmission-related dysfunctions are linked to many psychological conditions such as anxiety, depression, and movement disorders. 5-HT 7 is a member of the cell surface receptor GPCR superfamily and is regulated by the serotonin neurotransmitter. It has been the focus of intensive research efforts since its discovery, which was prompted by its presence in functionally important regions of the brain. The thalamus and hypothalamus have the highest 5-HT 7 receptor densities. They are also found in the hippocampus and cortex at higher densities. Thermoregulation, circadian rhythm, learning and memory, and sleep are all associated with the 5-HT 7 receptor. It is also suspected that this receptor may be involved in the control of mood, indicating that it may be a beneficial target for depression treatment. Several differently structured molecules such as aminotetralins, ergolines, arylpiperazines, indolylalkylamines, aporphines, and aryloxyalkyl-amines are known to bind to 5-HT 1A and 5-HT 7 receptor sites. In brain serotonin receptors 5-HT 1A and 5-HT 7 are strongly co-expressed in regions involved in depression. However, their functional interaction has not been identified. An overview of the 5-HT 1A and 5-HT 7 receptor ligands belonging to different chemical groups is mentioned in this review., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)