Islet amyloid polypeptide (IAPP) is a hormone cosecreted with insulin. IAPP proceeds through a series of conformational changes from random coil to β-sheet via transient α-helical intermediates. An unknown subset of these events are associated with seemingly disparate gains of function， including catalysis of self-assembly， membrane penetration， loss of membrane integrity， mitochondrial localization， and finally， cytotoxicity， a central component of diabetic pathology. A series of small molecule， α-helical mimetics， oligopyridylamides， was previously shown to target the membrane-bound α-helical oligomeric intermediates of IAPP. In this study， we develop an improved， microwave-assisted synthesis of oligopyridylamides. A series of designed tripyridylamides demonstrate that lipid-catalyzed self-assembly of IAPP can be deliberately targeted. In addition， these molecules affect IAPP-induced leakage of synthetic liposomes and cellular toxicity in insulin-secreting cells. The tripyridylamides inhibit these processes with identical rank orders of effectiveness. This indicates a common molecular basis for the disparate set of observed effects of IAPP.