Heart failure is a common and complex cardiovascular disease associated with elevated mortality and morbidity. Currently, there is no cure and the pharmacological therapy is based on a regimen of drugs often including &beta;-blockers where the goal is to slow down the progression and increase the quality of life. However, despite advances in both medicines and management, patients with heart failure generally experience a poor prognosis, making the disease a major public health problem. Exploring new suitable molecules that interfere selectively with targets in the &beta;-adrenergic/cAMP/PKA pathway may provide to abolish the challenges linked to the therapy. Upon sympathetic stimulation of &beta;-adrenergic receptors in cardiac myocytes, an activation of adenylyl cyclase and protein kinase A (PKA) leads to phosphorylation of several intracellular substrates, thereby increasing the rate and force of contraction. The key protein phospholamban (PLB) gets stimulated through this pathway and regulates the sarcoplasmic reticulum calcium pump. In its dephosphorylated state, PLB binds to sarcoplasmic Ca2+-ATPase (SERCA2) and suppresses its ATPase activity. The inhibitory effect is reversed by PKA-catalyzed phosphorylation, stimulating the re-uptake of cytosolic Ca2+ into the sarcoplasmic reticulum (SR). The A-kinase anchoring protein (AKAP), AKAP18&delta;, plays an important role in modulating PKA-dependent phosphorylations through association with the enzyme and recruiting it to its substrates like PLB, resulting in effective Ca2+- influx through SERCA2. The disruption of the AKAP18&delta;-PLB complex by specific molecules may prevent SERCA2 activity and possibly provide a more targeted therapy that protects the post-infarction heart against further damage. Based on earlier work, seven new compounds were synthesized and in vitro AlphaScreen technology was utilized to screen for their efficacy as inhibitors of the AKAP18&delta;-PLB interactions. One compound was identified as one of the most potent substances described in this project, and a chemical analysis of the molecules was conducted to obtain knowledge about the relationship between structure and activity.