Heart failure is a serious and disabling disease and the outlook for diagnosed patients is worrying. Modern treatment consists of a regimen of drugs often including β-blockers, which targets the regulatory mechanisms initiated by the body as a response to the reduced cardiac output. The adrenergic stimulation results in pacing of the heart, which in the long term is harmful and thus worsens the condition. β-blockade inhibits the adrenergic drive and delays the inevitable development of the disease. β-blockers have multiple adverse effects and contraindications that limits its clinical use. New targets downstream of regular adrenergic antagonists may serve to isolate wanted effects and abolish side effects. The adrenergic β-receptor signals through the cAMP-dependent PKA pathway and stimulates the phosphorylation of phospholamban (PLB). Phospholamban is a key regulator of heart rate and contractility. PLB inhibits the SR Ca2+-ATPase (SERCA2) in its dephosphorylated state, but releases SERCA2 upon phosphorylation by PKA. This allows SERCA2 to consume large amounts of energy in order to pump Ca2+ back into SR to complete the cardiac contraction period. The activity of SERCA2 is the rate limiting for the raise in heart rate and controls the length of the relaxation period and thus the rational filling of the heart. The anchoring protein AKAP18δ recruits PKA into close proximity with PLB, which results in specific phosphorylation and subsequent activation of SERCA2. Inhibition of the AKAP18δ-PLB complex would inhibit SERCA2 activity, isolate one effect of β-blockers and possibly protect the post-infarction heart against further damage. Small molecular disruptors of the AKAP18δ-PLB complex are a novel group of compounds and have not been described outside of this project. Thirteen new compounds were synthesized and their inhibitory effects on the AKAP18δ-PLB complex was tested using AlphaScreen technology. Highly effective compounds were identified and their structure were elucidated to define a pharmacophoric group for small molecular disruptors of the AKAP18δ-PLB complex.