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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Modulation of protein\u2013protein interactions (PPIs) by small molecules is a vital strategy in drug discovery. Nevertheless, due to the inherent nature of PPI interfaces, practical implementation of this approach remains a high-hanging fruit in medicinal chemistry. In this report, we develop a new line of PEX14\u2013PEX5 PPI inhibitors by homologation of a previously developed dibenzo[b,e]azepin-6(6H)-one scaffold. The challenging chemistry of 8-membered ring formation led to the development of novel PEX14 inhibitors featuring a 6+8+6 tricyclic system. The obtained analogs were tested for their capability of disrupting the PEX5-TbPEX14 PPI, as well as for in vitro activity against the T. brucei protist. 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