## 1 Introduction  
Over the last decades, \(\beta\)-blockers (i.e., antagonists of \(\beta\)-adrenergic receptors, \(\beta\)-ARs) have emerged as crucial therapeutic agents in the first-line treatment of acute and chronic diseases, particularly in the field of cardiovascular pathologies. \(\beta\)-ARs are G protein-coupled receptors used by endogenous catecholamines, especially noradrenaline and adrenaline [1], to modulate important physiological processes, such as blood pressure and cardiac activity [2]. Starting from their discovery, which gained Sir [PERSON] the Nobel Prize in 1936 [3], \(\beta\)-ARs have become crucial targets in the therapy of cardiovascular diseases [4]. Indeed, it is widely accepted that a deep relationship between \(\beta\)-ARs and the cardiovascular role of the sympathetic nervous system (SNS) exists. The history of \(\beta\)-blockers has been heavily influenced by the finding of three different \(\beta\)-ARs subtypes that paved the way for the design and the development of selective agonists and antagonists with specific therapeutic goals. It is known that \(\beta\)1-ARs are mainly expressed in the heart, \(\beta\)2-ARs in the smooth muscle of vasculature and airways and \(\beta\)3-ARs in the adipose tissue [2]. Cardiovascular therapies were deeply influenced and revolutionized when propranolol was introduced for the first time in the clinic for its ability to reducemyocardial oxygen demand under angina episodes [5,6]. Since then, three generations of \(\beta\)-ARs antagonists have been developed, namely nonselective, \(\beta\)1-cardioselective and \(\beta\)1-blockers with vasodilation activity [2]. In the heart, \(\beta\)1-ARs, \(\beta\)2-ARs and \(\beta\)3-ARs are all expressed and modulate cardiac performance by activating key intracellular pathways [7]. The homeostatic role of \(\beta\)-ARs in cardiac physiology is significantly highlighted by their strong phylogenetic conservation among species [8, 9, 10]. However, the effects on the myocardium are predominantly mediated by \(\beta\)1-ARs and \(\beta\)2-ARs, since in the healthy heart they are more expressed with respect to \(\beta\)3-ARs [4,11]. Stress stimuli, such as increased activity of the SNS, cause augmented plasma cat-echolamine levels by an adaptive physiological response. However, if stress and high catecholamine levels become chronic, the overactivation of \(\beta\)-ARs may result in an aberrant signaling network that leads to cardiac remodeling, fibrosis, arrhythmia, ventricular hypertrophy and heart failure [4,11]. In this perspective, the role of \(\beta\)-blockers to counteract detrimental effects of chronic stress assumes a critical significance. In terms of pharmacological classification, all \(\beta\)-blockers share a common feature that consists in their affinity/ability to bind \(\beta\)-ARs without evoking physiological effects. They are generally classified as competitive antagonists, so their effect can be overcome by increasing agonist concentration [12]. In particular, the blockade of cardiac \(\beta\)1-ARs is beneficial in myocardial hypertrophy, ischemia and failure, reducing both oxygen demand and renin production at a systemic level [13]. Much experimental and clinical evidence demonstrate that SNS overactivation and the resulting increase in catecholamine plasma levels is involved in the development of cardiac hypertrophy. In particular, the stimulation of \(\beta\)1-ARs, that in turn increases intracellular levels of cyclic-AMP and consequently of Ca2+, may account for the activation of the cardiac hypertrophic pathway [14,15]. In this view, the possibility to design and develop even more selective \(\beta\)1-ARs blockers still represents an important goal for cardiovascular translational research and an open field to be investigated [16, 17, 18, 19, 20]. In the literature, several compounds endowed with a carbazole structure or with a simplified carbazole moiety are reported as \(\beta\)-blockers.