Chroman-4-one and chromone based somatostatin β-turn mimetics

•Design and efficient synthesis of chroman-4-one and chromone-based β-turn mimetics.•The mimetics show somatostatin receptor agonist potencies in the low μM range.•Computer based conformational analysis confirms similarities with type II β-turns.•Chroman-4-ones and chromones are considered general scaffolds for β-turn mimetics.

A scaffold approach has been used to develop somatostatin β-turn mimetics based on chroman-4-one and chromone ring systems. Such derivatives could adopt conformations resembling type II or type II′ β-turns. Side chain equivalents of the crucial Trp8 and Lys9 in somatostatin were introduced in the 2- and 8-positions of the scaffolds using efficient reactions. Interestingly, this proof-of-concept study shows that 4 and 9 have Ki-values in the low μM range when evaluated for their affinity for the sst2 and sst4 receptors.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide