Alzheimer’s disease (AD), the most common form of dementia, is an irreversible neurodegenerative disorder associated with brain atrophy. The highest known risk factor for AD is advanced age, thus the severity of AD is expected to accelerate with the increased life expectancy of the world’s population. Currently available FDA approved drugs for AD only contribute to having minimal symptomatic relief. The amyloid-β (Aβ) hypothesis has been considered as one of the core pathological hallmarks of AD and the leading therapeutic target. Unfortunately, all the clinical trials of potential drug development based on Aβ clearance has failed to deliver significant outcome as of 2019. Thus, novel approaches are required to address the Aβ hypothesis. The cyclic neuropeptide somatostatin (SSTs) have been identified to promote the degradation of Aβ in CNS through the upregulation of the endopeptidase neprilysin (NEP). The SSTs subtype 4 (SST4) is highly expressed in cortex and hippocampus and several studies suggest that selective activation of SST4, could enhance NEP activity and thus reduce Aβ oligomers. Thus, the development of SST4 agonists as a therapeutic agent for AD can be a promising solution. This research aims to synthesize a new series of SST4 agonists based on the 3,4,5-trisubstituted-1,2,4-triazole scaffold and studies their structure-activity relationship in order to optimize the drug-like properties of the lead compound NNC-269100. The primary goal of the project was to synthesize SST4 agonists with enhanced physiochemical and drug-like properties i.e with improved solubility, binding affinity while maintaining high selectivity towards the SST4 receptor.