SAR of the arylpiperazine moiety of obeline somatostatin sst1 receptor antagonists

The SAR of over 50 derivatives of octahydrobenzo[g]quinoline (obeline)-type somatostatin sst1 receptor antagonist 1 is presented, focusing on the modification of its arylpiperazine moiety. Sst1 affinities in this series cover a range of five orders of magnitude with the best derivatives displaying subnanomolar sst1 affinities and >10,000-fold selectivities over the sst2 receptor subtype as well as promising pharmacokinetic properties.

Graphical abstractThe optimization of the arylpiperazine moiety in obeline-type somatostatin sst1 antagonists is presented, leading to compounds with subnanomolar sst1 affinities and >10,000-fold selectivities over the sst2 receptor subtype as well as promising pharmacokinetic properties.Figure optionsDownload full-size imageDownload as PowerPoint slide