Synthesis of 7-benzyl-5-(piperidin-1-yl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-1-ylamine and its analogs as bombesin receptor subtype-3 agonists

The original structure of a high-throughput screening hit obtained from an external vendor was revised based on multiple NMR studies. The active compound was re-synthesized via a novel route and its structure and biological activity as a BRS-3 agonist were unambiguously confirmed. Multi-gram quantities of the hit were prepared for pharmacokinetic and efficacy studies. The synthetic strategy allowed for the preparation of multiple analogs for SAR exploration.

Graphical abstractThe original structure assignment of 2, a high-throughput screening hit obtained from an external vendor, was revised based on multiple NMR studies. A novel synthetic route was developed for 2 and multi-gram quantities were prepared for pharmacokinetic and efficacy studies. Its activity on the BRS-3 receptor was confirmed, and additional SAR was explored.Figure optionsDownload full-size imageDownload as PowerPoint slide